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

Some Complexity Results for Robustness Verification for Binarized Neural Networks

arXiv:2606.18918v1 Announce Type: new Abstract: This paper studies the computational complexity of verification problems for Binarized Neural Networks (BNNs), where activations (and sometimes weights) are binary. We analyze two problems: satisfiability and robustness under uniform image occlusion. We show that BNN satisfiability is NP-complete via a reduction from Boolean satisfiability problem (SAT), and that uniform occlusion induces a piecewise-constant structure in the network output, enabling a polynomial-time robustness-checking algorithm.

02.
arXiv (quant-ph) 2026-06-12

A ribbon ZX calculus for gauge theory

arXiv:2606.13551v1 Announce Type: cross Abstract: ZX calculus provides a graphical formalism for reasoning about quantum processes, built from two interacting Frobenius algebras associated with the Z and X bases of a qubit. While it has found widespread application in quantum information and computing, its relationship to quantum field theory has only recently begun to be explored. In this work, we further develop this connection by providing a generalization of ZX calculus to two-dimensional Yang Mills theory with a compact gauge group. The key observation is that both frameworks can be organized around the Hopf Frobenius algebraic structure associated with a group algebra, which can in turn be described by the diagrammatics of two dimensional topological quantum field theory. Given the well known relationship between gauge theory and gravity in two and three dimensions, our work paves the way for applications of ZX to low dimensional gravity.

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

Unlocking Latent Dimensions: Exploring Representations of Large-Scale X-ray Scattering Data using Variational Autoencoders

arXiv:2606.14999v1 Announce Type: new Abstract: Scientific user facilities generate X-ray scattering data faster than traditional workflows can process them. We address this challenge across two settings, offline dataset exploration and live on-the-fly analysis. We train a domain-specific attention-based Convolutional Variational Autoencoder (C-VAE) on 1.5 million X-ray scattering images to learn low-dimensional representations capturing structural variation across diverse experimental conditions. The learned latent space reveals well-organized clusters and smooth trajectories reflecting experimental progression. It further supports controlled synthetic scattering image generation across diverse structural states. When deployed without retraining, the model organizes time-resolved film formation experiments at two synchrotron facilities into interpretable latent structures. Benchmarking against DINOv3 (ViT-7B), a general-purpose vision foundation model, demonstrates that domain-specific training yields more interpretable latent organization for scattering data. Both workflows are integrated within Latent Space Explorer, a component of the MLExchange platform, supporting interactive structural exploration across archived datasets and live experiments.

04.
arXiv (CS.CV) 2026-06-16

Wavelength-Multiplexed 2D Beam Steering via a Passive Diffractive Network

We introduce a wavelength-addressable diffractive optical network that transforms illumination wavelength into a high-dimensional control parameter for arbitrarily programmable 2D beam steering. The proposed passive architecture comprises cascaded spatially optimized diffractive layers, jointly designed using deep learning, to rapidly map distinct wavelengths to predefined/desired output angles. Unlike conventional single-layer dispersive optical elements, which are physically restricted to 1D linear mapping, this framework harnesses complex wavefront transformations to utilize the illumination wavelength as an intrinsic addressing key for arbitrary 2D beam steering, eliminating the need for mechanical scanning or electronic phase control. We numerically demonstrate wavelength-controlled beam steering across 625 wavelength channels spanning 400-750 nm, realizing a 25 x 25 array of independently addressable beam positions with subwavelength positioning accuracy and high channel fidelity. Unlike conventional gratings, which constrain wavelength routing to a linear trajectory, the proposed diffractive network performs nonlocal wavefront transformations, enabling arbitrary wavelength-to-angle mappings across a 2D field of view. We further validate the proposed framework experimentally in both the terahertz and visible spectral regimes, demonstrating wavelength-multiplexed beam steering using 3D fabricated passive diffractive layers at terahertz frequencies and phase-only spatial light modulators in the visible spectrum. This wavelength-addressable diffractive architecture establishes a compact and scalable paradigm for high-speed programmable beam steering, with potential applications in optical communications, routing, imaging, sensing, and emerging photonic information-processing systems.

05.
arXiv (CS.LG) 2026-06-18

FOSC-X: An Extended Framework for Optimal Local Cuts and Non-Horizontal Cluster Selection from Clustering Hierarchies

arXiv:2606.18972v1 Announce Type: cross Abstract: Extracting a flat clustering solution from a hierarchy is a common task in practical cluster analysis and can be formulated as an optimisation problem. Existing approaches focus on finding a single optimal solution. We introduce FOSC-X, a framework for extracting the top-M globally optimal flat clusterings from local, non-horizontal cuts of a hierarchical cluster tree, while optionally enforcing constraints on the number of clusters. This enables automatic identification of multiple high-quality alternative clusterings that capture different aspects of the hierarchical structure. Without constraints, the top-M problem can be solved in polynomial time using dynamic programming, exploiting the property that locally optimal partial candidates within subtrees can be combined to form globally optimal solutions while automatically determining the number of clusters. However, this can lead to solutions with numbers of clusters that are ultimately undesirable – e.g., too large to be meaningful or practically analysed within a particular application domain. Imposing cluster-count constraints breaks the optimality property underlying the unconstrained dynamic programming approach, since locally optimal partial candidates may no longer combine into feasible globally optimal solutions. FOSC-X addresses this challenge through a dynamic programming strategy that maintains compact sets of feasible candidates using lower and upper feasibility bounds while pruning infeasible or dominated combinations. The resulting method guarantees optimal rankings of the top-M solutions with linear-time complexity in the number of cluster nodes and dataset size, both with and without cluster-count constraints. Experiments show that FOSC-X efficiently reveals alternative clustering structures overlooked by single-solution extraction methods.

06.
bioRxiv (Bioinfo) 2026-06-16

DynamicDemiLog: A Single Sketch for Ultrafast Similarity, Frequency, and Cardinality Estimation

Probabilistic cardinality estimators (HyperLogLog), similarity sketches (MinHash), and frequency estimators (Count-Min Sketch) are fundamental approximate data structures that each target one primary problem. We present DynamicDemiLog (DDL), a sketch that unifies cardinality estimation, set similarity, containment, element frequency and composition in one tiny data structure built from a single pass over the input stream. Using an inverted index over 200,687 RefSeq sketches (159,567 organisms), DDL performs all-to-all sketch similarity comparison of the full database in 30 seconds (128 threads, indexed) - over 375x faster per query than Mash's brute-force all-to-all comparison of 91,282 sketches, or 31x faster without the index, at double the sketch resolution. DDL extends the LogLog register with a mantissa: each register stores a floating-point-encoded hash value consisting of an integer exponent (the leading-zero count) and a fractional mantissa (the sub-leading-zero bits), rather than the integer leading-zero count alone. This preserves enough hash information for meaningful register-by-register comparison - a property that standard 6-bit registers lack - while improving on LogLog's cardinality estimation machinery, including DynamicLogLog's early exit mask for high-throughput streaming. With a default 10 mantissa bits (16-bit registers, 2,048 buckets, 4 KB), DDL achieves a per-register false-match rate of 0.018% on unrelated random same-size sets (compared to 17.0% for LL6, a basic HyperLogLog implementation), enabling Weighted Kmer Identity (WKID), Average Nucleotide Identity (ANI), containment, and completeness estimation from register comparison alone. A 16-bit per-register observation counter provides element frequency information at trivial additional computation cost, and an additional byte tracks element composition (GC content, for biological data). Furthermore, DDL's high-specificity registers enable an inverted index structure (DDLIndex) that answers similarity queries against a database of N sketches in O(B + M) time, where M is the number of matching index entries, compared to O(NxB) for pairwise comparison.

07.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

Authors:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

08.
arXiv (CS.CV) 2026-06-17

DiFlow-TTS: Compact and Low-Latency Zero-Shot Text-to-Speech with Discrete Flow Matching

Zero-shot text-to-speech (TTS) has made significant progress in replicating unseen voices, yet balancing generation quality and inference efficiency remains challenging. Autoregressive models suffer from high latency, while diffusion-based approaches are constrained by training-time configurations. Moreover, most flow-based methods operate in continuous space, which introduces optimization challenges because continuous token spaces are inherently more complex than discrete ones. To address these limitations, we propose DiFlow-TTS, a novel zero-shot TTS framework based on discrete flow matching. The model consists of a deterministic Phoneme-Content Mapper for linguistic modeling and a Factorized Discrete Flow Denoiser that simultaneously generates prosody and acoustic token streams. Experimental results demonstrate the effectiveness of our approach across multiple evaluation metrics.

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

Greedy Coordinate Diffusion: Effective and Semantically Coherent Adversarial Attacks via Diffusion Guidance

arXiv:2606.15531v1 Announce Type: new Abstract: Fine-tuning aligned language models on benign tasks (e.g. math tutoring) systematically breaks safety guardrails, even when training data contains no harmful content. While mechanistic approaches have shed light on where alignment resides in model weights, they do not by provide a general formal framework for deriving guarantees about when fine-tuning degrades it – leaving the field without principled tools for predicting or preventing alignment collapse. We develop a local geometric framework through geometric analysis of parameter-space trajectories and apply it to understand the fragility of alignment in fine-tuning. While first-order analysis suggests orthogonal updates are safe, we prove this is illusory: the curvature of the fine-tuning loss induces second-order acceleration that can induce second-order drift into alignment-sensitive regions. We formalize a construct of our framework as the Alignment Instability Condition (AIC), three geometric properties that, when present, are sufficient to guarantee degradation. Our main result proves quartic onset of alignment degradation along gradient-flow trajectories, determined by how sharply alignment depends on specific parameters and how strongly tasks couple to these parameters. These findings yield formal sufficient conditions under which static first-order protection can fail under gradient descent. We further empirically validate the framework's foundations, showing that the Fisher Information Matrix provides a proxy for the degree of safety degradation across diverse fine-tuning.

10.
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.

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

S23DR 2026: End-to-End 3D Wireframe Prediction via DETR-Style Set Prediction with Contrastive Denoising

Authors:

We present WireframeDETR, our submission to the Structured Semantic 3D Reconstruction (S23DR) 2026 Challenge, which requires predicting a 3D building wireframe from multi-view COLMAP point clouds. Our method applies DETR-style set prediction directly to 3D point clouds, producing wireframes as sets of edge coordinate pairs without any intermediate vertex detection stage. We introduce three technical contributions: (1) contrastive denoising training that stabilises noisy Hungarian matching in early epochs; (2) a multi-scale encoder that aggregates the last encoder layer outputs via learned scalar weights; and (3) progressive auxiliary loss weighting that concentrates gradient signal on the decoder layers that most benefit from it. Our model achieves a public test HSS of 0.575 (F1~=~0.664, IoU~=~0.516) and a best validation HSS of 0.534 on the cleaned val split.

12.
arXiv (CS.CV) 2026-06-17

Vision-language models for chest radiography do not always need the image

Medical vision-language models report strong chest radiograph accuracy, and this is increasingly read as evidence that they use the image. That inference is unsafe: a model exploiting finding-name priors scores like one that reads the scan, and no standard benchmark separates them. We introduce a causal audit that intervenes on the image, occluding the relevant region, occluding an irrelevant one, and swapping in another patient's same-label scan, and combines three behavioral metrics to test whether a correct answer depends on the image. Across nine systems, a text-only model with no image access reaches within 5.7 accuracy points of the best multimodal one, and a 119-billion-parameter multimodal model is statistically indistinguishable from a 7-billion text-only baseline. The audit splits the cohort into three models that ignore the image, one that is unstable, and five that use it selectively, for a subset of findings; the categories hold across a second dataset, resolution, and prompt phrasing. Against board-certified radiologists, a text-only model is statistically indistinguishable from a radiologist's accuracy while grounding at zero, whereas the image-using models ground at radiologist-comparable rates. Reported confidence flags ungrounded answers only when a model uses the image. Grounding audits, not accuracy, should gate clinical deployment.

13.
arXiv (CS.CV) 2026-06-16

TIMI: Training-Free Image-to-3D Multi-Instance Generation with Spatial Fidelity

Precise spatial fidelity in Image-to-3D multi-instance generation is critical for downstream real-world applications. Recent work attempts to address this by fine-tuning pre-trained Image-to-3D (I23D) models on multi-instance datasets, which incurs substantial training overhead and struggles to guarantee spatial fidelity. In fact, we observe that pre-trained I23D models already possess meaningful spatial priors, which remain underutilized as evidenced by instance entanglement issues. Motivated by this, we propose TIMI, a novel Training-free framework for Image-to-3D Multi-Instance generation that achieves high spatial fidelity. Specifically, we first introduce an Instance-aware Separation Guidance (ISG) module, which facilitates instance disentanglement during the early denoising stage. Next, to stabilize the guidance introduced by ISG, we devise a Spatial-stabilized Geometry-adaptive Update (SGU) module that promotes the preservation of the geometric characteristics of instances while maintaining their relative relationships. Extensive experiments demonstrate that our method yields better performance in terms of both global layout and distinct local instances compared to existing multi-instance methods, without requiring additional training and with faster inference speed.

14.
arXiv (CS.AI) 2026-06-15

A Comparative Study of Deep Learning Architectures for Multi-Horizon Behavioural Forecasting for Mobile Health

arXiv:2606.14604v1 Announce Type: cross Abstract: Wearable devices and smartphones generate rich behavioural time series that can support proactive health interventions, yet systematic comparisons of modern forecasting architectures for these data are lacking. In particular, it remains unclear how models generalise across populations, how different architectures respond to participant-level fine-tuning and how forecasting accuracy degrades across multi-day horizons. We benchmark six deep learning architectures, two zero-shot Foundation Models (FM) and statistical baselines on three public datasets encompassing over 800 participants, reporting per-feature metrics for step counts, screen time and sleep duration across 1-8 day horizons. We further conduct a per-feature personalisation study across all six architectures and assess FM transferability across dataset sizes and temporal granularities. Our key findings are: (i) no single architecture dominates, PatchTST leads among trained models while the three runners-up (TCN, MLP, Transformer) show no meaningful performance difference; (ii) the FM TimesFM matches or exceeds trained models zero-shot, especially in low-data regimes and (iii) participant-level fine-tuning reduces per-feature RMSE by 16-60\%, with sleep benefiting most and step counts least. These results provide practical guidance on architecture selection, FM applicability and personalisation strategies for mobile health forecasting. To the best of our knowledge, this is the first study to jointly evaluate modern deep learning, FMs and personalisation for multi-horizon behavioural forecasting from wearables.

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

ALIGNBEAM : Inference-Time Alignment Transfer via Cross-Vocabulary Logit Mixing

Domain fine-tuning degrades the safety of large language models: fine-tuned specialists readily comply with harmful prompts framed in domain language. Existing inference-time defenses that mix logits from a safe anchor model require both models to share a vocabulary, which rules them out for the cross-family specialists where safety is most degraded. We present ALIGNBEAM, a training-free method that lifts this restriction by translating anchor logits into the target model's vocabulary token-by-token at each decoding step; a small LLM judge then selects the safest among K candidate continuations. No weights are changed, and the safety-utility trade-off can be tuned at deployment without retraining. Across both cross-vocabulary and same-vocabulary evaluation pairs, ALIGNBEAM substantially raises refusal on adversarial benchmarks while keeping task accuracy and inference overhead within practical bounds. The results show that safety alignment can be transferred between model families at inference time, without touching either model's weights.

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

Reliability-Calibrated Edge-IoT Early Fault Warning for Rotating Machinery with a Physics-Guided Tiny-Mamba Transformer

arXiv:2601.21293v3 Announce Type: replace-cross Abstract: Industrial Internet of Things (IIoT) systems increasingly rely on distributed vibration sensing to support predictive maintenance of rotating machinery. In practical deployments, however, raw signal upload is costly and alarm decisions must be made locally under limited computation, changing operating conditions, and strict nuisance-alarm budgets. This paper presents a reliability-calibrated edge-IoT early-warning framework, in which a compact Physics-Guided Tiny-Mamba Transformer (PG-TMT) acts as the representation module and an extreme value theory (EVT) layer converts streaming anomaly scores into event-level alarm episodes. PG-TMT combines a depthwise-separable convolutional stem, a Tiny-Mamba state-space branch, and a lightweight local Transformer to capture transient, long-horizon, and multichannel degradation cues under batch-size-one inference. To improve auditability, temporal attention is projected to the frequency domain and softly aligned with analytical bearing fault-order bands. EVT calibration, dual-threshold hysteresis, and trimmed-tail fitting provide controllable false-alarm intensity even when healthy calibration data are imperfect. Experiments on CWRU, Paderborn, XJTU-SY, and an industrial pilot demonstrate that the proposed framework improves PR-AUC, reduces detection delay under a controlled nuisance-alarm budget, and remains robust to structured interference, metadata uncertainty, compound fault mixtures, and domain transfer. With a sub-1 MB footprint and Jetson p99 latency below 7 ms, the framework supports calibrated and interpretable early warnings for IIoT predictive maintenance.

17.
arXiv (CS.CV) 2026-06-16

Track2View: 4D-Consistent Camera-Controlled Video Generation via Paired 3D Point Tracks

Re-rendering an existing video from a novel camera viewpoint requires the output to follow the prescribed camera trajectory while preserving the appearance and dynamics of the original scene across every frame. Existing methods rely on per-frame pose embeddings, noisy point-cloud renderings, or implicit learned correspondences, none of which provides an explicit, temporally continuous link between source and target pixels. We propose Track2View, which conditions a video diffusion transformer on paired 3D point tracks: sparse trajectories of scene points projected into both the source and target camera views. These tracks provide explicit spatiotemporal correspondences that are temporally continuous by construction, encoding what content should appear where and when. At the core of Track2View is a dual-view track conditioner that transfers visual context from source to target view through parameter-free geometric operations and learned temporal aggregation, ensuring generalization to arbitrary camera trajectories without memorizing specific motions. We further introduce a data curation pipeline that extracts one-to-one track correspondences by running a 3D point tracker on temporally concatenated multi-camera view pairs. On a 400-video benchmark spanning static and dynamic scenes, Track2View achieves state-of-the-art results across visual quality, view synchronization, and camera accuracy, reducing rotation error by 30-65% and translation error by 61-72% relative to leading baselines. Project page is available at this https URL: https://qjizhi.github.io/track2view

18.
arXiv (quant-ph) 2026-06-11

A Geometric Family of Correlations Containing the Quantum Singlet

arXiv:2606.12045v1 Announce Type: new Abstract: We introduce a geometrically constrained hidden-variable framework that generates a family of correlations parametrized by a boundary function, within which the quantum singlet correlation appears as a particular member. Exact expressions for the correlation function are derived. Several structural results are established, including admissibility conditions, symmetry properties, a universal stationary point of the associated CHSH function, and an exact relation between the CHSH value at $\nu=\pi/4$ and a geometric contrast measure defined on the underlying hidden-variable distributions. Rather than treating the quantum singlet correlation as an isolated target to be reproduced, the present framework places it within a broader geometric structure of correlations. These results suggest the existence of a nontrivial geometric structure underlying the family of correlations and motivate the search for a principle capable of selecting the quantum singlet solution from within that family.

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

Cost-Optimal LLM Routing with Limited User Feedback under User Satisfaction Guarantees

arXiv:2606.19376v1 Announce Type: cross Abstract: Inference costs for large language model (LLM) applications are rapidly growing, driven by surging demand and rising infrastructure cost. Users expect high-quality responses, and in commercial settings this is formally codified in Service Level Agreements (SLAs), creating a fundamental tension between cost and quality. Recent progress on cost-aware LLM request routing has shown potential to resolve this tension, but existing approaches rely on complete feedback signals, offline training, extensive per-workload tuning, and most lack SLA guarantees or inference-time adaptivity. We introduce SLARouter, an online routing algorithm that learns a cost-optimal policy from the sparse, one-sided user feedback available in production systems. SLARouter provides theoretical guarantees for both cost optimality and strict SLA compliance. Experiments across a wide range of LLM benchmarks show that SLARouter satisfies SLA constraints without the need for per-benchmark tuning, reducing operating cost by up to 2.2x over existing baselines.

20.
arXiv (quant-ph) 2026-06-11

Dissociative recombination and ion-pair formation in $\mathrm{HeH^+}$ isotopologues: A time-dependent wave-packet study including rotational coupling

arXiv:2606.11352v1 Announce Type: cross Abstract: We present a comprehensive theoretical investigation of dissociative recombination (DR) and resonant ion-pair (RIP) formation in $\mathrm{HeH^+}$ isotopologues using time-dependent wave-packet propagation methods. Nuclear dynamics are treated on a set of 23 coupled electronic states, including $^2\Sigma$, $^2\Pi$, and $^2\Delta$ symmetries, in both adiabatic and strictly diabatic representations, with rotational couplings explicitly included. Reaction cross sections are computed over collision energies ranging from 0 to 50 eV. The results reveal that inclusion of a large manifold of resonant states and rotational couplings significantly enhances the DR cross section relative to earlier theoretical studies. In the diabatic representation, $^2\Sigma$ states dominate the recombination dynamics, while in the adiabatic representation, $^2\Pi$ and $^2\Delta$ states contribute significantly at low collision energies. For RIP formation, two different diabatization schemes yield systematically larger cross sections than previous models, highlighting the sensitivity of ion-pair production to electronic coupling structure. Isotopic effects are examined, showing a clear inverse dependence of cross section magnitude on reduced mass. The present results underscore the importance of multi-state coupling and nonadiabatic effects in accurately describing electron-molecule collision processes in primordial and astrophysical plasmas.

21.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

22.
arXiv (CS.LG) 2026-06-11

Probabilistic Contrastive Pretraining for Multi-task ADME Property Prediction

arXiv:2606.11508v1 Announce Type: new Abstract: Accurate prediction of absorption, distribution, metabolism, and excretion (ADME) properties is critical to drug discovery, but remains challenging because ADME endpoints are noisy, interdependent, and often data-limited. We propose a molecular graph-transformer pretraining framework that combines chemistry-specific self-supervision with contrastive mutual information machine learning (cMIM). Our method encodes molecular graphs into latent variables, reconstructs SMILES strings from the graph-derived latent codes, and augments the contrastive objective with domain-specific self-supervised chemistry tasks. Rather than treating these tasks as auxiliary regularizers with separately tuned loss weights, we formulate reconstruction, contrastive discrimination, and chemistry-specific supervision as unit-weighted log-probability factors in a single probabilistic latent-variable objective. For fine-tuning, we propose a multi-task GNN readout architecture with task-specific multilayer perceptron heads, preserving shared representation learning while mitigating negative transfer and improving the modeling of heterogeneous, nonlinear task relationships. Across Biogen, ExpansionRX, and ChEMBL-MT, the resulting Contrastive KERMT pretraining improves over the KERMT baseline by 7.6%, 9.9%, and 9.5% respectively (averaged over significantly-improved endpoints). Adding ADME-adjacent molecules to the pretraining corpus further improves transfer, and the contrastive component sharpens chemically meaningful latent neighborhoods.

23.
arXiv (CS.CV) 2026-06-18

SAMA: Semantic Anchor-aligned Augmentation for Unified Low-Resource Multimodal Information Extraction

Multimodal Information Extraction (MIE)-covering tasks such as Multimodal Named Entity Recognition (MNER), Relation Extraction (MRE), and Event Extraction (MEE)-is essential for understanding multimedia content but remains constrained by severe data scarcity. Although data augmentation is a promising remedy, existing approaches are impeded by coarse cross-modal alignment and fragmented, task-specific designs that fail to exploit shared semantic knowledge. To overcome these limitations, we introduce Semantic Anchor-aligned Multimodal Augmentation (SAMA), a unified framework for generating high-fidelity, task-aware synthetic data. SAMA constructs structured semantic anchors from ground-truth labels to guide a Collaborative Multi-Experts Multimodal Large Language Model (CME-MLLM), which integrates a Universal Adapter for shared semantics with Task-Specific Adapters to produce diverse yet constraint-compliant textual samples. For image synthesis, SAMA employs an Anchor-Preserving Diffusion mechanism that uses anchor-weighted prompts and latent conditioning to maintain critical semantic anchors while diversifying visual contexts. To eliminate the need for manual verification, SAMA further introduces a Dual-Constraint Filtering module that selects synthetic samples based on both cross-modal consistency and anchor fidelity. Extensive experiments across benchmark datasets for MNER, MRE, and MEE demonstrate that SAMA consistently outperforms state-of-the-art augmentation baselines under both fully supervised and low-resource settings, underscoring its versatility, robustness, and effectiveness.

24.
arXiv (CS.CV) 2026-06-15

Diffusion-Refined Segmentation and Vision-Language Interpretation for Pediatric Brain Tumor MRI

Accurate pediatric brain tumor segmentation remains challenging due to limited annotated data, heterogeneous imaging phenotypes, diffuse tumor boundaries, and class imbalance across tumor subregions. Here, we present a two-stage deep learning framework for improving multi-modal pediatric brain MRI segmentation and clinical interpretation. First, we evaluate 3D Res U-Net and Swin-UNETR baselines on BraTS-PEDs MRI scans, using four co-registered modalities to predict tumor core, whole tumor, and enhancing tumor regions. Second, we introduce diffusion-based refinement models conditioned on coarse Swin-UNETR predictions, including a 3D DDPM refiner and MedSegDiff. Conditioning substantially improves diffusion stability and performance, particularly for enhancing tumor boundary segmentation. Conditioned MedSegDiff achieves the strongest boundary agreement with the lowest HD95. Finally, predicted tumor volumes and representative segmentation overlays are integrated with a multimodal language model to generate structured radiology-style reports. Together, our results suggest that coarse-to-refined diffusion segmentation can improve pediatric tumor boundary delineation and support end-to-end interpretable AI-assisted neuro-oncology workflows.

25.
Nature Medicine 2026-06-11

Clinical Profile and Genomic Characterization of the 2026 Bundibugyo Virus Index Case in Uganda

Bundibugyo virus disease (BVD) remains a high-consequence threat in Eastern and Central Africa, where cross-border mobility, nonspecific early symptoms, and delayed recognition can obscure transmission. In this case report, we describe Uganda’s 2026 BVD index case: a male patient who traveled from the Democratic Republic of the Congo to Uganda and was admitted to a private hospital in Kampala on 11 May 2026 after more than two weeks of vomiting and diarrhea, with epigastric pain, weakness, and hiccups. He deteriorated rapidly, developing acute kidney injury, pulmonary edema, hepatic dysfunction, hypoxemia, delirium, atrial flutter, possible disseminated intravascular coagulation, and multiorgan failure, and died on 14 May. A posthumous EDTA whole-blood specimen tested at the Central Emergency Response and Surveillance Laboratory was positive for orthoebolavirus RNA and confirmed as Bundibugyo virus (BDBV) by RT-qPCR. Sequencing achieved 99% genome coverage at ≥100× depth. The 2026 BDBV genome formed a distinct lineage approximately equidistant from the 2007–2008 Butalya and 2012 Isiro variants, differing by 216–227 nucleotides (~1.2% sequence divergence). Here, we demonstrate the value of fatality surveillance, private-sector surveillance, diagnostic optimization through national specimen referral, and rapid molecular-genomic diagnostics for early detection, transmission chain interruption, and public health response coordination.