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

OTCHA: Optimal Transport-driven Confidence-aware Latent Hub Alignment for Multi-View Medical Image Classification

Multi-view imaging, such as mammography and chest radiography, is a standard component of clinical practice. However, medical images are often unregistered and contain view-specific artifacts or irrelevant background cues that can obscure diagnostically relevant findings. Many existing methods directly fuse per-view representations, allowing such irrelevant content to contaminate the fused embedding and reducing robustness under varying view configurations. We propose OTCHA, a confidence-aware latent hub token alignment module based on optimal transport (OT) that refines patch tokens before fusion for multi-view classification. OTCHA introduces a set of learnable latent hub tokens shared across views. For each view, we compute an OT plan between patch tokens and hub tokens that jointly considers feature similarity and geometry, and augment the OT formulation with token-conditional dustbins to enable partial matching and discard irrelevant tokens. The resulting transport plan provides token-wise matching confidence, which gates hub-mediated message passing and weights a novel optimal-transport-based representation alignment loss to stabilize refinement. Experiments on three multi-view medical image datasets demonstrate consistent improvements over competing baselines across diverse anatomies and view configurations. Our code is available at https://github.com/labhai/OTCHA.

02.
medRxiv (Medicine) 2026-06-12

Metastatic Patterns and Treatment Characteristics of Triple-Negative Breast Cancer in Nigeria: A Retrospective Cohort Study

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. It is associated with limited targeted treatment options, early relapse, and a high propensity for visceral metastasis. Data describing metastatic patterns and treatment characteristics of TNBC in Nigeria remain limited. Methods: This retrospective descriptive cohort study included 869 patients with TNBC managed at the Medserve-LUTH Cancer Center, Lagos University Teaching Hospital, Nigeria between June 2019 and June 2024. Demographic, clinicopathologic, metastatic, and treatment-related data were extracted from electronic medical records. Descriptive statistics were used to summarize patient characteristics, metastatic patterns, and treatment profiles. Associations between metastatic disease and selected clinicopathologic and treatment variables were explored using Pearsons chi-square test. Complete-case analysis was applied throughout. Results: The mean age at presentation was 52.09 {+/-} 12.26 years. Most patients were married (79.1%), postmenopausal (64.3%), and of Yoruba ethnicity (56.8%). Advanced disease predominated, with Stage III and Stage IV disease accounting for 42.9% and 35.6% of cases, respectively. Invasive ductal carcinoma was the most common histologic subtype (77.0%), while Grade II tumours constituted 51.3% of graded cases. Surgery was performed in 73.1% of patients, predominantly mastectomy (70.9% of surgical procedures). Chemotherapy was administered to 83.2% of patients, most commonly anthracycline-based regimens (41.8%), while radiotherapy was delivered to 63.5% of patients, with hypofractionated schedules of 42-43 Gy in 15-16 fractions accounting for 47.2% of radiotherapy courses. Metastatic disease was documented in 32.9% of evaluable patients. Lung metastasis was the most frequent site (62.5%), followed by bone (46.3%), regional lymph node invasion (38.5%), liver (23.0%), and brain (22.6%). Tumour grade and histologic subtype were not significantly associated with metastatic disease, whereas radiotherapy exposure demonstrated a significant association with metastatic status ({chi}{superscript 2} = 10.35, p = 0.001). Conclusion: TNBC in this Nigerian cohort was characterized by advanced-stage presentation, invasive ductal predominance, extensive use of multimodality treatment, and substantial visceral metastatic burden. Lung metastasis was the most common metastatic site. These findings provide contemporary real-world data on TNBC in Nigeria and highlight the continuing need for earlier diagnosis, timely referral, and sustained investment in comprehensive cancer care services.

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

Vocabulary Dropout for Curriculum Diversity in LLM Co-Evolution

Co-evolutionary self-play, where one language model generates problems and another solves them, promises autonomous curriculum learning without human supervision. In practice, the proposer quickly converges to a narrow distribution of problems that satisfy the reward function. This diversity collapse renders the curriculum uninformative for the solver, stalling the co-evolutionary loop. We introduce vocabulary dropout, a random mask applied to the proposer's output logits during both policy training and curriculum generation, as a lightweight mechanism to sustain diversity. The mask is hard and non-stationary, preventing the proposer from locking into fixed token sequences. Training Qwen3-4B and Qwen3-8B on mathematical reasoning via R-Zero, we find that vocabulary dropout sustains proposer diversity across lexical, semantic, and functional metrics throughout training. It also yields solver improvements averaging +4.4 points at 8B, with the largest gains on competition-level benchmarks. Our findings suggest that explicit action-space constraints, analogous to the structural role that game rules play in classical self-play, can help sustain productive co-evolution in language. Vocabulary dropout is one simple instantiation of this principle.

04.
arXiv (CS.CV) 2026-06-17

Reload-Mamba: Hierarchical Anti-Dilution State-Space Modeling for Multi-Class Semantic Segmentation

Mamba-based state space models offer linear-time long-range modeling for high-resolution dense prediction, but sequential state-space propagation can attenuate boundary-sensitive and detail-sensitive responses that are critical in multi-class semantic segmentation. We propose Reload-Mamba, a semantic segmentation framework that addresses this propagation-induced response dilution through three segmentation-specific designs: (i) a boundary-supervised local detail prior that is explicitly trained with ground-truth boundary masks to identify regions requiring response restoration; (ii) a class-uncertainty-aware Reload Gate that incorporates per-pixel class entropy from a pre-reload auxiliary head as an additional gating signal, a formulation that is informative only under multi-class dense prediction; and (iii) a hierarchical multi-level Reload mechanism that applies anti-dilution refinement at three decoder levels and fuses the restored representations top-down. Built upon a ConvNeXt-Tiny encoder with a multi-scale decoder and four-directional Mamba scanning with pixel-wise directional attention, Reload-Mamba achieves 47.9% single-scale (48.9% multi-scale) mIoU on ADE20K and 83.2% single-scale mIoU on Cityscapes. With ResNet-101 + COCO pre-training under the standard DeepLab-style protocol, Reload-Mamba reaches 87.8% mIoU on PASCAL VOC 2012 val. Controlled ablations show that each of the three segmentation-specific designs contributes beyond a direct port of the prior anti-dilution architecture proposed for binarization, cumulatively improving over the direct-port baseline by +2.2 mIoU on ADE20K.

05.
arXiv (CS.CV) 2026-06-15

FEMOT: Multi-Object Tracking using Frame and Event Cameras

Conventional RGB cameras have been widely used in multi-object tracking due to their ability to capture rich appearance and semantic information. However, their performance is often degraded under complex real-world challenges, such as motion blur, low illumination, and overexposure. Bio-inspired event cameras offer high temporal resolution and high dynamic range, providing complementary cues under extreme scenarios. Nevertheless, RGB-event multi-object tracking remains underexplored due to the lack of large-scale and well-annotated datasets. To address this issue, we propose FEMOT, a large-scale RGB-event multi-object tracking dataset that covers diverse real-world scenarios and 14 challenging attributes. With both RGB and event data as well as high-quality annotations, FEMOT provides a reliable platform for systematically evaluating RGB-event multi-object tracking methods. Based on FEMOT, we retrain and evaluate over ten strong trackers, thereby establishing a comprehensive benchmark for future research. Furthermore, we propose FEMOTR, a multimodal tracking framework that decouples RGB and event features and fuses them in the frequency domain, thereby effectively exploiting their complementary characteristics for robust object localization and identity association. Extensive experiments on FEMOT and DSEC-MOT datasets demonstrate the effectiveness of the proposed method. The source code and benchmark dataset have been released on https://github.com/Event-AHU/FEMOT.

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

An Ontology-Guided Multi-Anchor Graph Retrieval Framework for Traffic Legal Liability Determination

Traffic law liability determination is critical for assigning legal penalties, requiring the simultaneous identification of interdependent statutory provisions across multiple legal dimensions. However, existing retrieval-augmented generation methods suffer from a multi-dimensional retrieval bottleneck: single axis architectures compress complex legal queries into a single pathway, causing interdependent statutory dimensions to be overlooked. To address this, we propose OMAGR, an ontology-guided framework that decomposes queries into ontology-aligned anchors and executes parallel graph retrieval across each dimension, ensuring independent retrieval across dimensions before fusion. To evaluate the proposed method, we created the TrafficLaw-QA dataset, an expert-validated benchmark dataset containing 200 questions and 527 legal provisions. Results show that TrafficOmni-RAG outperforms baselines on Context Precision and Faithfulness metrics. The findings demonstrate that parallel multi-anchor retrieval effectively resolves the multi-dimensional retrieval bottleneck, offering a promising direction for traffic law liability determination research.

07.
arXiv (CS.AI) 2026-06-11

When Do Data-Driven Systems Exhibit the Capability to Infer?

arXiv:2606.11769v1 Announce Type: new Abstract: The European AI Act is the first comprehensive regulation of artificial intelligence (AI), setting out extensive obligations, particularly for so-called high-risk and general-purpose AI systems. A key distinguishing feature of AI systems under the AI Act is the capability to infer. Since the AI Act does not clearly define what inference is, there is a gray area for certain data-driven systems. A specific example is credit scoring systems, which are listed by Annex III of the AI Act. At the same time, however, these are often implemented using statistical models for which it is unclear whether they have the capability to infer and thus fall under the AI definition of the AI Act at all. Motivated by statistical learning theory, this work develops a framework for grading different levels of the capability to infer. Based on the AI Act and the Commission Guidelines on the definition of an artificial intelligence system, we analyze which levels constitute sufficient capability to infer within the meaning of the AI Act and where further regulatory clarity is needed. We illustrate the framework by creating two realistic credit scoring workflows and show whether and where inference occurs in them. Our analysis illustrates that not only individual models but the entire data processing workflow must be considered. It also shows that the involvement of human experts during development can have significant influence on the capability to infer. Code can be found at https://github.com/fraunhofer-iais/inference-framework-creditscorecards.

08.
arXiv (CS.CV) 2026-06-12

OR-Action: Multi-Role Video Understanding with Fine-Grained Actions

Fine-grained understanding of operating room (OR) activity could enable workflow-aware assistance, yet remains difficult due to clutter, occlusions, and limited sensing. The prevailing approach to model this environment is scene graphs as an interpretable representation of OR interactions. Converting their frame-wise relational predictions into temporally extended, fine-grained actions however, is challenging without explicit temporal modeling. To enable a principled temporal evaluation of current OR understanding methods, we introduce the first action-centric benchmark built on a publicly available ego-exocentric OR dataset by defining a fine-grained, multi-role action taxonomy and generating dense action segments via distillation from ground-truth scene graph state changes. Experiments on this benchmark show that current scene graph prediction methods struggle to model temporal structure, even when adding explicit modeling through Graph Neural Networks. We therefore introduce a vision-only temporal model that outperforms graph-based methods significantly when using all available egocentric video as input. Building on this model we also introduce a novel multi- to single-view feature alignment strategy that improves single-view performance on multi-role action recognition, mitigating the need for extensive egocentric video capture. Benchmark and code will be released upon acceptance.

09.
arXiv (CS.LG) 2026-06-18

DIPHINE: Diffusion-based $\Phi$-ID Neural Estimator

arXiv:2606.18997v1 Announce Type: new Abstract: Uncovering the true informational architecture of real-world complex systems requires disentangling how their components uniquely store, redundantly share, and synergistically integrate information over time. Integrated Information Decomposition ($\Phi$ID) is a framework for decomposing the information dynamics of multivariate systems into sixteen non-overlapping atoms that characterize redundant, unique, and synergistic modes of information storage, transfer, and integration. Existing methods to compute $\Phi$ID are restricted to Gaussian or discrete systems, preventing its application to continuous non-Gaussian dynamical systems. We address this limitation by proposing DIPHINE (Diffusion-based $\Phi$-ID Neural Estimator), the first neural estimator that leverages score-based diffusion models to jointly estimate all the mutual information terms required by $\Phi$ID from a single amortized network, recovering the sixteen atoms through Möbius inversion. We provide a theoretical analysis of error propagation through the inversion, showing that the Jacobian of the mapping from mutual informations to atoms is integer-valued and that the synergy-to-synergy atom is provably the hardest to estimate. We demonstrate accurate recovery of ground-truth atoms on synthetic benchmarks, superior performance compared to established mutual information estimators, and the ability to extract physiologically interpretable information-dynamic structure on an application involving real data without any distributional assumptions.

10.
arXiv (CS.AI) 2026-06-12

Real-rootedness of the Poincaré polynomials of $\overline{\mathcal M}_{0,n}$: an AI-assisted proof

arXiv:2605.29151v2 Announce Type: replace-cross Abstract: We prove real-rootedness for the Poincaré polynomial \[ P_n(t)=\sum_{i=0}^{n-3} \dim H^{2i}(\overline{\mathcal M}_{0,n};\mathbb{Q})t^i \] of the Deligne–Mumford moduli space $\overline{\mathcal M}_{0,n}$ of stable $n$-pointed rational curves, proving a conjecture of Aluffi–Chen–Marcolli. The proof starts from the Keel–Manin–Getzler recurrence, but its main new idea is a bivariate deformation $F_m(y,t)$ of the Poincaré polynomial. This deformation reveals a hidden interlacing structure not visible in the one-variable recurrence. For fixed $t

11.
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.

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

Organize then Retrieve: Hierarchical Memory Navigation for Efficient Agents

Large language model (LLM) agents struggle with long-horizon tasks due to their inherent statelessness, requiring all task-relevant information to be encoded in growing input contexts. The resulting degraded reasoning quality, increased inference cost, and higher latency necessitate efficient working memory mechanisms. However, existing approaches either rely on lossy compression or similarity-based retrieval, which often fail to capture temporal structure and causal dependencies required for multi-step agentic tasks. In this work, we present HORMA, a Hierarchical Organize-and-Retrieve Memory Agent that organizes experience into a file-system-like hierarchical structure, where summarized entities are linked to the corresponding raw trajectories, enabling efficient access without losing detailed information. HORMA decomposes working memory into two stages: structured memory construction and navigation-based retrieval. The construction module iteratively refines how experiences are structured by distinguishing between failures caused by missing information and those caused by misleading or overloaded context. The navigation module retrieves task-relevant context by traversing the hierarchy using a lightweight agent trained with reinforcement learning to select minimal yet sufficient context, thereby reducing latency along the critical execution path. Across ALFWorld, LoCoMo, and LongMemEval, HORMA improves task performance under constrained context budgets while requiring at most 22.17% of the baseline token usage in long conversation tasks. Compared to existing methods, it consistently achieves better efficiency-performance trade-offs and generalizes effectively to unseen tasks.

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

All-Mem: Agentic Lifelong Memory via Dynamic Topology Evolution

Lifelong interactive agents are expected to assist users over months or years, which requires continually writing long term memories while retrieving the right evidence for each new query under fixed context and latency budgets. Existing memory systems often degrade as histories grow, yielding redundant, outdated, or noisy retrieved contexts. We present All-Mem, an online/offline lifelong memory framework that maintains a topology structured memory bank via explicit, non destructive consolidation, avoiding the irreversible information loss typical of summarization based compression. In online operation, it anchors retrieval on a bounded visible surface to keep coarse search cost bounded. Periodically offline, an LLM diagnoser proposes confidence scored topology edits executed with gating using three operators: Split, Merge, and Update, while preserving immutable evidence for traceability. At query time, typed links enable hop bounded, budgeted expansion from active anchors to archived evidence when needed. Experiments on LoCoMo and LongMemEval-s show improved retrieval and QA over representative baselines. The code is available at https://github.com/LvCan926/All-Mem.

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

Implementing Hamiltonian Renormalization Group Flow on Quantum Computers with VAPOR

arXiv:2606.11306v1 Announce Type: cross Abstract: While Hamiltonian Lattice Gauge Theory is gaining traction, today's limited numerical capacity leaves simulations affected by discretization errors. This motivates the implementation of renormalization group (RG) techniques to find discretization-error-free operators. To this end, we introduce VAPOR, a variational quantum algorithm that decomposes operators into Pauli strings, identifies RG flow orbits, and determines fixed points of a naively discretized operator. We illustrate this using a toy model of a kinematic operator in a symmetry-restricted SU(2) Yang-Mills theory.

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

Hubs or Fringes: Pretraining Data Selection via Web Graph Centrality

The performance of modern language models depends critically on pretraining data composition. Yet existing data selection methods rely on auxiliary classifiers for document scoring or mixture optimization, adding computational overhead and dependence on labeled data. We propose WebGraphMix, a lightweight data selection framework that computes structural centrality scores over the Common Crawl host-level web graph and uses them to vary the proportion of central versus peripheral documents in the pretraining mixture. We hypothesize that central hosts expose models to reusable abstractions, while peripheral hosts encode specialized, long-tail knowledge. WebGraphMix computes centrality scores efficiently at web scale, requiring no model training, labeled data, or downstream supervision. We integrate WebGraphMix into the DataComp-LM pipeline and train models at 400M and 1B parameter scales with 8B and 28B tokens respectively, evaluating on 23 tasks ranging from factual knowledge to symbolic reasoning. Our experiments show that central and peripheral web regions encode complementary capabilities. Mixture combining both at a ratio of 1:1 achieves 41.4% on average, compared to 39.8% for uniform sampling. Combining structural scores with document-level quality classifier scores further improves performance to 43.8%. These findings demonstrate that web graph topology is a meaningful axis for pretraining data curation, capturing information that is largely orthogonal to existing content-based approaches.

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

InvDesMobility: a reliability-gated first-principles feedback framework for closed-loop materials discovery

arXiv:2606.16133v1 Announce Type: cross Abstract: Inverse materials design starts from target functionality and searches for structures that can realize it. Its value in closed-loop discovery depends not only on prediction performance, but also on whether expensive first-principles results are independently validated, provenance-recorded, and admitted as feedback only when evidence is sufficient. This is especially important for composite properties such as carrier mobility, where a final scalar value hides intermediate quantities, fit quality, convergence history, and workflow assumptions. Here we present InvDesMobility, a reliability-gated first-principles feedback framework that integrates multi-agent automated DFT, evidence stratification, generative structure proposal, acquisition ranking, and auditable release. Using 516 2DMatPedia-derived candidates, the workflow produced 280 QC-passed materials and 573 retained carrier-direction seed channels after channel-level reliability gating. These records were split into two feedback objects: relaxed structures updated the generative model, while retained mobility channels trained the acquisition model and set validation priority. Over multiple iterations, InvDesMobility screened 2.4 x 10^6 structures, submitted 102 candidates for DFT validation, and retained 86 reliability-gated generated channels across 41 formulas. Overall, the main contribution is not a fixed list of high-mobility materials, but a transferable feedback contract that makes closed-loop inverse design both useful and auditable when learning from expensive calculated properties. All source data, retained feedback records, and workflows are available at https://github.com/DreamLufei/invDesMobility, with an accompanying evidence website at https://dreamlufei.github.io/invDesMobility/.

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

MentalMARBERT: Domain-Adaptive Pre-training and Two-Stage Fine-Tuning for Arabic Mental Health Disorders Detection

Detecting mental health disorders from Arabic social media text remains challenging due to dialectal variation, informal language, limited high-quality annotated resources, and severe class imbalance. While English mental health natural language processing (NLP) has progressed substantially, Arabic multi-class disorder classification remains insufficiently studied. This study proposes a two-phase framework for Arabic mental health text classification. In phase 1, three Arabic pre-trained language models, AraBERT, CAMeLBERT, and MARBERT, undergo Domain-Adaptive and Task-Adaptive Pretraining (DAPT and TAPT) using a large-scale corpus of unlabeled Arabic mental health tweets. The adapted models are evaluated under a unified protocol to identify the most effective backbone model. In phase 2, the selected model is assessed across four configurations combining single-stage and hierarchical two-stage classification architectures with full fine-tuning and Low-Rank Adaptation (LoRA). To support this study, we constructed a novel annotated Arabic mental health dataset comprising 50,670 tweets across six categories, with strong inter annotator agreement (Krippendorff's Alpha = 0.733, average pairwise agreement = 0.797). Experimental results show that the domain-adapted MARBERT (MentalMARBERT) achieves statistically significant improvements over baseline models in both accuracy and macro-F1. The hierarchical two-stage architecture combined with full fine-tuning achieves the best overall performance, reaching a macro-F1 of 0.861 and an accuracy of 0.877. These findings demonstrate the effectiveness of domain-specific adaptive pretraining and hierarchical classification for Arabic mental health disorder detection.

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

Leveraging Deep Learning for Object and Position Recognition of Load Carriers for Autonomous Logistics Vehicles

arXiv:2606.16042v1 Announce Type: cross Abstract: This work explores the use of artificial intelligence in mobile robotics to achieve autonomous detection and pose estimation of load carriers for automated pickup. A deep neural network is designed to recognize predefined landmarks on the carrier from RGBD data; these landmarks are then used to compute the carrier's pose. The network operates directly on RGBD images to estimate landmark positions, which form the basis for determining the carrier's location. The approach is validated in extensive experiments and comprises both software and hardware implementations. A deep learning-based framework is presented to detect load carriers and estimate their pose for use with autonomous logistics vehicles. Our method uses a convolutional neural network to identify characteristic reference points on the carrier from RGBD input and computes its pose by combining these inferred landmarks with prior geometric knowledge. Experiments show that the resulting accuracy is sufficient for reliable load carrier detection in industrial environments, confirming the suitability of the method for autonomous intralogistics applications.

19.
medRxiv (Medicine) 2026-06-10

Towards the Virtual Amyotrophic Lateral Sclerosis Patient: Inferring Cortical Excitability through Whole-Brain Dynamical Modeling

Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem neurodegenerative disorder in which motor-neuron degeneration is accompanied by widespread alterations in cortical dynamics. Among its most reproducible neurophysiological signatures is cortical hyperexcitability, yet how this local excitability imbalance shapes distributed whole-brain activity remains poorly understood. Here, we combined source-reconstructed resting-state MEG data, tractography-informed whole-brain modeling, and simulation-based inference to investigate whether ALS-related alterations in large-scale brain dynamics can be mechanistically explained by changes in cortical excitability. First, we characterized empirical brain dynamics using complementary features spanning regional activity amplitude and variability, functional connectivity, and avalanche-based metrics. These analyses revealed significant alterations in ALS patients relative to healthy controls, as well as associations with clinical impairment and disease staging. To mechanistically interpret these changes, we employed a reduced Wong-Wang whole-brain model in which local recurrent excitation modulates emergent large-scale neural dynamics. Simulations showed that increasing excitability systematically reproduced the empirical dynamical signatures observed in ALS. We then applied a simulation-based inference framework to estimate latent excitability parameters directly from empirical observations. Whole-brain model inversion revealed increased excitability in ALS patients compared with controls. The recovered excitability parameter was associated with disease staging, supporting its clinical relevance as a model-derived descriptor of ALS progression. Finally, by extending the model to estimate frontal and non-frontal excitability separately, we found that ALS-related alterations were predominantly associated with increased frontal excitability, whereas non-frontal regions appeared comparatively less affected. The recovered parameters related to disease staging. Together, these findings provide a mechanistic framework linking altered large-scale brain dynamics in ALS to selective cortical hyperexcitability, explaining how local excitability changes can give rise to global network reorganization. More broadly, they show how computational model inversion can recover latent multiscale pathophysiological processes from empirical neural recordings, offering a non-perturbative alternative to complex experimental paradigms typically required to causally probe local-to-global mechanisms.

20.
bioRxiv (Bioinfo) 2026-06-21

Expanding the GUSome: Structure-guided identification and characterization of gut microbial β-glucuronidases

The gut microbiome-encoded {beta}-glucuronidase (GUS) enzymes have a significant effect on human physiology through their deglucuronidation activity on endogenous and exogenous glucuronides. GUS activity also significantly influences the pharmacokinetics, efficacy and toxicity of various drugs including chemotherapeutic drugs. Given their crucial role in drug metabolism, GUS enzymes have emerged as promising targets for therapeutic intervention. Here, we have identified and characterized 79 unique GUS enzymes through a structure-guided approach. Structural modelling of these GUS enzymes revealed a conserved core and active-site residues with significant variations in the number and nature of the C-terminal domains. A new classification system based on the number and type of additional C-terminal domains is presented for the GUS proteins. Further, GUS enzymes have been categorized into different loop categories linked to their substrate preferences. The relationship between domain architecture and loop-type is explored by sequence similarity network analysis. We could successfully express, purify and validate GUS processing capability of a panel of identified GUS proteins. The nature of oligomer organization has been deciphered by SEC and DLS studies. Further, we have identified additional GUS enzymes capable of processing SN-38G, glucuronidated form of anticancer drug, irinotecan. These newly identified GUS enzymes will offer valuable insights into gut microbial GUS diversity and their role in understanding the population-specific drug-induced adverse effects on human health.

21.
Nature (Science) 2026-06-17

Analysis of 173,303 exomes and genomes in the Pakistan Genome Resource

Naturally occurring loss-of-function variants in human genes enable drug target discovery because they mimic pharmacological inhibition of proteins. However, the study of these genetic variants is constrained by their rarity. Sequencing of diverse populations, particularly those enriched in familial relatedness, has been postulated to promote discovery of rare genetic variants1–3. Here we present the Pakistan Genome Resource, a South Asian biobank with high familial relatedness comprising 173,303 participants, who collectively carry naturally occurring homozygous loss-of-function variants in 6,476 genes. We describe the genetic architecture of this population, associations between genes and biomarkers, the distribution of loss-of-function variants across molecular pathways, and recall-by-genotype studies of therapeutically relevant genes. The Pakistan Genome Resource expands the catalogue of human genetic variants, provides a comprehensive genetic reference resource for the Pakistani population, and demonstrates the value of studying diverse cohorts to advance human health. The Pakistan Genome Resource compiles biobank data from 173,303 individuals with high familial relatedness, broadening the catalogue of human genetic variation and establishing a population-specific genomic reference for Pakistan.

22.
arXiv (CS.LG) 2026-06-12

Simplex-Constrained Sparse Bagging: Transitioning from Uniform Priors to Sparse Posteriors in Ensemble Learning

arXiv:2606.13589v1 Announce Type: new Abstract: We present Simplex-Constrained Sparse Bagging (SCSB), a mathematically rigorous framework for post-training compression and probability calibration of bootstrap-based bagging ensembles. Standard bagging ensembles (such as Random Forests, Bagged SVMs, and Bagged Neural Networks) assign uniform voting power to all constituent estimators. However, this naive uniform prior ignores the varying local competence of base estimators and contributes to model overconfidence. We formulate ensemble pruning and calibration as a joint optimization problem over the probability simplex by minimizing the Out-Of-Bag (OOB) loss. To induce sparsity, we address the theoretical "L1-simplex paradox" – the mathematical reality that the L1 norm is constant on the simplex and fails to prune – by introducing a concave quadratic penalty. SCSB is model-agnostic and achieves up to 96% ensemble compression, yielding linear inference speedups and superior probability calibration (lowered Expected Calibration Error) while preserving or enhancing generalization accuracy.

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

Motion-Focused Latent Action Enables Cross-Embodiment VLA Training from Human EgoVideos

Training generalist Vision-Language-Action(VLA) models typically requires massive, diverse robotic datasets with high-fidelity action annotations. While egocentric human manipulation videos are abundant and capture significant environmental diversity, the absence of action labels makes them difficult to use in conventional training paradigms. To address this, we propose a latent-action-based framework designed to extract general action priors from unlabeled human videos. The architecture features a Hybrid Disentangled VQ-VAE that decouples motion dynamics from environmental backgrounds through physical masks, enabling the construction of a cross-embodiment action codebook. By pre-training on human videos with the codebook, the VLM backbone learns deep representations of action intent. For adaptation to specific embodiments, we introduce an intent-perception decoupling strategy where the VLM predicts the action intent while a separate frozen visual encoder provides state-specific features to the action expert, thereby reducing action hallucinations. Results in simulation and real-world environments show that our method, pre-trained exclusively on unlabeled human videos, performs competitively with state-of-the-art VLA models trained on massive annotated datasets, requiring only 50 trajectories for downstream adaptation.

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

Can LLMs Accurately Score Medical Diagnoses and Clinical Reasoning?

arXiv:2604.14892v3 Announce Type: replace-cross Abstract: Evaluating medical AI systems using expert clinician panels is costly and slow, motivating the use of large language models (LLMs) as alternative adjudicators. Here, we evaluate an LLM Jury, composed of three frontier AI models, for scoring 3334 diagnoses on 300 real-world low- and middle-income country (LMIC) hospital cases. Both LLM- and clinician-generated diagnoses are scored against expert panel diagnoses across four dimensions: diagnosis, differential diagnosis, clinical reasoning, and negative treatment risk. The LLM Jury scores are compared with expert and independent re-scoring panel scores to assess error metrics, inter-rater agreement, severe-risk errors, and the effect of post hoc calibration using isotonic regression. In our data, we find that: (i) the uncalibrated LLM Jury scores preserve ordinal agreement with the expert clinician panel scores, but are systematically lower; (ii) the probability of severe-risk errors is lower for the LLM Jury than the human expert re-score panels; (iii) the LLM Jury combined with LLM diagnoses can be used to identify diagnoses at high risk of error, enabling targeted expert review and improved panel efficiency; (iv) the calibrated LLM Jury scores and rankings of diagnosing agents show excellent agreement with those of the primary expert panels; (v) LLM Jury models show no self-preference bias, they did not score diagnoses generated by their own underlying model or models from the same vendor more (or less) favourably than those generated by other models. Together, these results provide evidence that a calibrated LLM Jury is a trustworthy and reliable proxy for expert clinician evaluation in medical AI benchmarking. Confirming these findings in other clinical settings is an important direction for future work.

25.
arXiv (CS.LG) 2026-06-16

Filtered Conformal Ellipsoids for Graph-Native Time Series

arXiv:2606.17014v1 Announce Type: new Abstract: Joint prediction sets for multivariate time series should control a single event while adapting to cross-coordinate dependence. We study filtered conformal ellipsoids: a frozen state-space filter emits a one-step predictive mean and covariance, and split-conformal calibration is applied to the resulting Mahalanobis scores. The filter is used to choose the ellipsoid shape; conformal calibration chooses the scalar radius, so the construction benefits from a learned predictive covariance without relying on Gaussian tail probabilities for coverage. The main difficulty is that filtered scores are dependent and learned recurrent filters need not contract in their raw hidden state; we therefore analyse contraction in an observable predictive-law quotient that identifies hidden states producing the same future sequence of emitted Gaussian laws. Under a stable Bayes Gaussian-projection filter, covariance bounds, and a finite-horizon observability Fisher condition, small excess Gaussian negative log-likelihood implies contraction of the learned emitted laws. Combined with a threshold-autocovariance envelope this yields a Chebyshev-type approximate coverage bound for filtered split-conformal prediction under dependence; a sharper Bernstein-type bound requires an additional geometric-mixing concentration assumption. Under Gaussian oracle realisability we also obtain a near-oracle log-volume comparison within the class of conditionally valid Gaussian ellipsoid rules. We instantiate the framework with a GCN-GRU filter with diagonal-plus-low-rank covariance. On moderate-size graph-native traffic benchmarks (METRLA-$20$ and PEMSBAY-$50$), the learned filter gives sharper at-target ellipsoids than static-covariance and non-filter baselines; at full-graph scale and on non-graph-native datasets, factor and copula baselines can be stronger.