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01.
arXiv (CS.CL) 2026-06-16

A Systematic Evaluation of Large Language Models for PTSD Severity Estimation: The Role of Contextual Knowledge and Modeling Strategies

Large language models (LLMs) are increasingly being used in a zero-shot (generative) fashion to assess mental health conditions, yet we have limited knowledge on what factors affect their accuracy. In this study, we use a clinical dataset of natural language narratives and self-reported PTSD severity scores from 1,437 individuals to comprehensively evaluate the performance of 11 state-of-the-art LLMs. To understand the factors affecting model's assessment accuracy, we systematically varied (i) contextual knowledge prompted to the models like subscale definitions, distribution summary, and interview questions, and (ii) modeling strategies including zero-shot vs few shot, amount of reasoning effort, model sizes, structured subscales vs direct scalar prediction, output rescaling and nine ensemble methods. Our findings indicate that (a) LLMs are most accurate when provided with detailed construct definitions and context of the narrative, even exceeding human raters agreement with self-reported scores; (b) increased reasoning effort leads to better estimation accuracy; (c) performance of open-weight models (Llama, DeepSeek) plateaus beyond 70B parameters while closed-weight (gpt-o3-mini, gpt-5) alternatives improve with newer generations; and (d) best performance is achieved when ensembling a supervised model with the zero-shot LLMs. Beyond agreement with self-reports, LLMs' estimates discriminated PTSD severity from depression, anxiety, and alcohol use, and prospectively predicted future mental healthcare expenditure. Together, these results suggest that contextual knowledge and modeling strategies meaningfully affect accuracy and clinical utility of LLM-based assessments of PTSD severity.

02.
arXiv (CS.CV) 2026-06-11

BiWM: Advancing Open-Source Interactive Video World Models with Bidirectional Autoregression

Transitioning bidirectional video diffusion models into an autoregressive paradigm improves the interactivity of video world models, but existing causal pipelines need many stages (control fine-tuning, autoregressive training, causal initialization, few-step distillation) and still trail bidirectional models in quality due to error accumulation. Recent world models such as Yume-1.5 and Matrix-Game-3.0 instead adopt a bidirectional autoregressive approach, gaining fidelity and stable long-horizon rollout from self-correcting error propagation, yet open-source frameworks (e.g., minWM) support only causal models. We present BiWM, the first full-stack framework for interactive video world models under the bidirectional autoregressive paradigm, jointly optimizing generation quality and inference speed. From a pretrained video backbone, BiWM injects camera control by fine-tuning, then runs a few-step Distribution Matching Distillation (DMD) stage that turns the backbone into an action/camera-controllable world model: just two training stages instead of four in minWM, converging in a few hundred steps on 8xH200 GPUs. A single recipe spans Wan2.1-1.3B, Wan2.2-5B, HunyuanVideo-1.5-8B, and LTX-2.3-22B, and also supports secondary fine-tuning of existing bidirectional models. BiWM enables real-world camera control where minWM loses controllability, integrates pluggable history compression (FramePack-style and PackForcing-style) for long rollouts, and offers an optional NVFP4 4-bit training/inference pipeline. To counter DMD's mode-seeking degradation, we add GAN and mass-covering forward-KL objectives that preserve scene dynamics. We open-source BiWM for resource-constrained research and high-fidelity environment simulation.

03.
arXiv (CS.AI) 2026-06-17

Evaluating Interactive 2D Visualization as a Sample Selection Strategy for Biomedical Time-Series Data Annotation

arXiv:2603.26592v2 Announce Type: replace-cross Abstract: Reliable machine-learning models in biomedical settings depend on accurate labels, yet annotating biomedical time-series data remains challenging. Algorithmic sample selection may support annotation, but evidence from studies involving real human annotators is scarce. Consequently, we compare three sample selection methods for annotation: random sampling (RND), farthest-first traversal (FAFT), and a graphical user interface-based method enabling exploration of complementary 2D visualizations (2DVs) of high-dimensional data. We evaluated the methods across four classification tasks in infant motility assessment (IMA) and speech emotion recognition (SER). Twelve annotators, categorized as experts or non-experts, performed data annotation under a limited annotation budget, and post-annotation experiments were conducted to evaluate the sampling methods. Across all classification tasks, 2DV performed best when aggregating labels across annotators. In IMA, 2DV most effectively captured rare classes, but also exhibited greater annotator-to-annotator label distribution variability resulting from the limited annotation budget, decreasing classification performance when models were trained on individual annotators' labels; in these cases, FAFT excelled. For SER, 2DV outperformed the other methods among expert annotators and matched their performance for non-experts in the individual-annotator setting. A failure risk analysis revealed that RND was the safest choice when annotator count or annotator expertise was uncertain, whereas 2DV had the highest risk due to its greater label distribution variability. Furthermore, post-experiment interviews indicated that 2DV made the annotation task more interesting and enjoyable. Overall, 2DV-based sampling appears promising for biomedical time-series data annotation, particularly when the annotation budget is not highly constrained.

04.
medRxiv (Medicine) 2026-06-11

PCRAgent: A Multi-Agent Framework for Transforming Noisy clinical conversations into Structured Pre-Consultation Medical Records and Reusable Clinical Data Resources

In primary care and outpatient settings, clinically important patient information is often embedded in fragmented, ambiguous, repetitive, and noisy communication between physicians and patients. This limits physicians ability to obtain a clear preconsultation overview of symptoms, history of present illness, and visit intent, while also preventing real world clinical dialogues from being reused in hospital information systems and medical artificial intelligence applications. To address this challenge, we developed PCRAgent, a centrally coordinated multi agent framework for preconsultation clinical information organization. Guided by physician inquiry logic, PCRAgent identifies, extracts, corrects, and standardizes patient-reported information from noisy consultations. Its coordinated modules including error detection, semantic editing, output control, contextual memory, and intent recognition enable robust parallel handling of spelling errors, repetitions, grammatical inconsistencies, medical ambiguities, and non-medical interference. A traceable edit list records intermediate corrections and context, allowing iterative refinement without redundant modifications. PCRAgent generates two complementary outputs. One is a PreConsultation Clinical Report for rapid physician review. The other is a Structured Clinical Conversation Dataset for hospital data construction and downstream AI applications. In evaluations using 220000 strongly perturbed consultations, PCRAgent maintained high robustness, achieving a clinical information accuracy of 4.99 out of 5 and key element completeness of 5 out of 5, outperforming GPT4o. Expert review of Chinese and English dialogues confirmed high clinical accuracy of 4.85 out of 5 and high safety of 4.79 out of 5. Multicenter validation in real-world outpatient workflows further demonstrated practical utility. These findings indicate that PCRAgent can efficiently transform noisy and unstructured consultations into physician ready reports and AI ready structured data, improving outpatient efficiency, reducing cognitive burden, ensuring information completeness, supporting precise decision-making, and enabling high-quality reuse of clinical data.

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

UniDexTok: A Unified Dexterous Hand Tokenizer from Real Data

Dexterous hands are essential for fine-grained manipulation, but their hardware designs vary substantially across embodiments. Differences in kinematics, joint definitions, and degrees of freedom make it difficult to define a shared state representation compared with parallel grippers. As a result, dexterous-hand data remains fragmented and difficult to use for joint training. In this work, we propose the Unified Dexterous Hand Model (UDHM), which maps human and robot hand states into a shared 22-DoF semantic interface. Based on UDHM, we introduce UniDexTok, a retargeting-free state tokenizer that learns embodiment-conditioned discrete tokens from standardized real joint states. UniDexTok provides a unified representation for heterogeneous dexterous hands without relying on retargeting or simulation data. Compared with the recent baseline UniHM, UniDexTok reduces MPJAE from 15.63 degrees to 0.16 degrees and MPJPE from 18.51 mm to 0.18 mm, corresponding to error reductions of 98.98% and 99.03%, respectively. These results improve reconstruction from centimeter-scale to sub-millimeter accuracy. Experiments further show that data from other embodiments improves target-embodiment reconstruction accuracy, demonstrating the benefit of cross-embodiment tokenization. UniDexTok also shows strong zero-shot and few-shot reconstruction ability when new dexterous hands are introduced.

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

Tabular Foundation Models for Clinical Survival Analysis via Survival-Aware Adaptation

arXiv:2606.12006v1 Announce Type: cross Abstract: Predicting time-to-event outcomes such as mortality is a fundamental task in clinical decision-making, commonly addressed through survival analysis. While classical statistical and deep learning approaches have been widely studied, they typically require task-specific training and sufficient labeled data. Recent advances in tabular foundation models offer a new paradigm by learning general-purpose representations for structured data. However, their applicability to censored time-to-event prediction in clinical settings remains underexplored, as typical applications are restricted to discrete classification rather than survival analysis tasks. In this work, we propose a lightweight adaptation approach for applying tabular foundation models to clinical survival analysis by directly training a survival-aware head on top of the pretrained representations. We study representative architectures, including TabPFN, TabDPT, and TabICL, and adapt them using a multi-task logistic regression (MTLR) head to model right-censored time-to-event outcomes. We evaluate this approach on a diverse set of public survival benchmarks and two large-scale ICU cohorts, MIMIC-IV and eICU. Our results show that this transfer learning approach achieves competitive or superior performance compared to strong baselines. On MIMIC-IV, TabDPT-FT-MTLR reaches a C-index of 0.856, corresponding to a relative improvement of +1.4% over the best non-FM baseline (DeepSurv, 0.844) and +6.7% over the best zero-shot model (0.802). On eICU, TabICL-FT-MTLR achieves 0.797, yielding gains of +1.7% (DeepSurv, 0.784) and +6.4% (0.749), respectively. These findings highlight the importance of combining pretrained tabular representations with survival-aware objectives and suggest that tabular foundation models provide a practical and effective alternative for clinical survival prediction.

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

MortarBench: Evaluating Mortgage Loan Origination Agents

arXiv:2606.19416v1 Announce Type: new Abstract: Loan origination is the process by which a lender creates a new loan, from application and underwriting through approval and funding. This process serves a critical role in evaluating the eligibility and level of risk posed by an applicant. Recently, firms have begun using mortgage loan agents to augment human loan officers, despite a lack of any public benchmark. To fill this gap, we present MortarBench, a loan origination agent benchmark. MortarBench uses a financial data synthesis and mutation pipeline to generate examples with broad edge case coverage that match real-world distributions and questions. We find that state-of-the-art large language models (LLMs) perform poorly, with closed-source models achieving at most 77.1\% exact match accuracy. We also discover systematic biases in LLM perception of foreignness related to non-English names. Noting these weaknesses, we introduce CRIT, a confidence calibration framework. Our method increases accuracy to 80.5\% while improving risk management steering and reducing bias.

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

A2D2: Fine-Tuning Any-Length Discrete Diffusion for Adaptive Decoding

arXiv:2606.13565v1 Announce Type: new Abstract: Discrete diffusion models offer a simple and stable likelihood-based framework for sequence generation, recently extended to any-length settings via token insertion. Principled reward-guided fine-tuning for any-length discrete diffusion, however, remains largely unexplored. We introduce Fine-Tuning Any-Length Discrete Diffusion for Adaptive Decoding (A2D2), a unified framework for reward-guided fine-tuning of any-length discrete diffusion models via joint optimization of the insertion and unmasking policies together with a quality-based inference schedule. We derive the Radon-Nikodym derivative for the joint insertion-unmasking path measures, enabling theoretically guaranteed convergence to the intractable reward-tilted sequence distribution without requiring target samples. Building on this, we establish unmasking and insertion quality as tractable approaches for minimizing decoding error and introduce the Adaptive Joint Decoding (AJD) loss, which provably yields the optimal path measure that generates the reward-tilted distribution. Empirically, A2D2 improves reward optimization while enhancing generation flexibility and accuracy over prior fixed-length fine-tuning and inference-time guidance methods.

09.
medRxiv (Medicine) 2026-06-22

MinderCare: protocol for a mixed-methods evaluation of a digitally enabled dementia care service.

Introduction and aims Dementia is a growing public health challenge affecting millions of people worldwide. It is a progressive condition that increases the risk of infections, falls, hospital admissions, dependence in activities of daily living, safety issues such as wandering, care home transfers, and death. New ways of supporting people living with dementia (PLWD) at home are urgently needed. We describe the MinderCare study which evaluates a digitally enabled care model that integrates low-burden sensor-based remote monitoring within a nurse-led clinical service. Methods and analysis In this mixed-methods study, we will recruit 100 people with confirmed or suspected dementia living at home and deploy the Minder remote monitoring system for at least 12 months. A detailed characterisation of the cohort will be obtained, including cognition, frailty, participant and carer wellbeing, functioning, and quality of life. The feasibility, acceptability, sustainability, and resource requirements of the service will also be assessed. Low-cost sensors provide information about behaviour, environment and physiology from the home. Machine-learning algorithms have been used to develop digital biomarkers of infection, sleep, night-time behaviours, daily activities and routines, and the effects of clinical events and treatment. These will be assessed through clinical reports of sensor-derived data that include anomaly alerts provided to the clinical teams. Algorithms will be assessed for their clinical utility and acceptability. The comparative-effectiveness component will be designed as a target trial emulation using linked electronic health-record data to construct a time-indexed external usual-care control cohort. The primary comparative outcome will be Days Alive and Out of Hospital (DAOH) over 12 months from the activation-index date, with healthcare utilisation, costs, institutionalisation and mortality assessed as secondary outcomes. DAOH and estimated MinderCare effects will also be examined across prespecified strata of baseline inpatient utilisation. Ethics and dissemination Ethical approval has been granted by the North East Newcastle and North Tyneside 2 Research Ethics Committee, and the study has received confirmation of capacity and capability by the Imperial College Healthcare NHS Trust. Study findings will be disseminated to patients, health and social care professionals, and policymakers through peer-reviewed publications and conference presentations. Study registration number: ISRCTN14997677 and NIHR portfolio CPMSID 63023.

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

Emergent retokenization symmetry in large language models: phenomenology and applications

Tokenization introduces representational redundancy: under a fixed token vocabulary, every byte string admits many valid token encodings, or segmentations, that decode to the same surface string. However, given a prompt, most language model tokenizers break this representational symmetry by returning a canonical segmentation. Training only on canonical segmentations should influence inference behavior, and there is little reason to expect models to respect segmentation symmetry on downstream tasks. We find that this symmetry partially emerges during training. Here, we probe this emergent symmetry through experiments testing token compositional understanding, representation diversity, and task focused benchmark performance. We primarily use retokenization – replacing a prompt's canonical tokenization with an alternative segmentation while preserving its bytes exactly. Relative to other prompt perturbations, retokenization is unusually clean because it isolates segmentation effects without changing syntax, semantics or surface form. We use retokenization to study sensitivity and robustness to semantically identical input representations across pretraining and post-training. Moreover, this partial retokenization symmetry suggests a distinct inference-time sampling axis. While temperature sampling generates diverse outputs from the model using its next-token probability distribution, retokenization generates diversity from the model's internal computations through semantically equivalent input representations. We find that while this retokenization sampling strategy can hurt performance on easy problems, it can also recover solutions that conventional sampling does not find. Overall, our work presents retokenization as a simple yet powerful probe of large language models, shedding light on compositional understanding and prompt sensitivity, and offering a novel sampling strategy.

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

Learning Patient-Specific Disease Dynamics with Latent Flow Matching for Longitudinal Imaging Generation

Understanding disease progression is a central clinical challenge with direct implications for early diagnosis and personalized treatment. While recent generative approaches have attempted to model progression, key mismatches remain: disease dynamics are inherently continuous and monotonic, yet latent representations are often scattered, lacking semantic structure, and diffusion-based models disrupt continuity with random denoising process. In this work, we propose to treat the disease dynamic as a velocity field and leverage Flow Matching (FM) to align the temporal evolution of patient data. Unlike prior methods, it captures the intrinsic dynamic of disease, making the progression more interpretable. However, a key challenge remains: in latent space, Auto-Encoders (AEs) do not guarantee alignment across patients or correlation with clinical-severity indicators (e.g., age and disease conditions). To address this, we propose to learn patient-specific latent alignment, which enforces patient trajectories to lie along a specific axis, with magnitude increasing monotonically with disease severity. This leads to a consistent and semantically meaningful latent space. Together, we present $\Delta$-LFM, a framework for modeling patient-specific latent progression with flow matching. Across three longitudinal MRI benchmarks, $\Delta$-LFM demonstrates strong empirical performance and, more importantly, offers a new framework for interpreting and visualizing disease dynamics.

12.
bioRxiv (Bioinfo) 2026-06-21

DeepCDS: Ab initio coding sequence prediction in prokaryotic short reads

Accurate coding sequence prediction in short prokaryotic metagenomic reads remains challenging due to sequence fragmentation, unknown sequence origins, and sequencing errors. Here we introduce DeepCDS, a deep learning-based ab initio coding sequence predictor trained on short prokaryotic sequences with and without simulated Illumina-like sequencing errors. DeepCDS integrates ESM-2 protein language model embeddings with nucleotide-level information to predict complete and fragmented coding sequence regions. Benchmarking on 215 phylogenetically diverse prokaryotic organisms demonstrates that DeepCDS consistently outperforms current state-of-the-art methods in coding sequence detection, start and stop codon localization, and robustness to different sequencing error profiles, while remaining operational at shorter sequence lengths than existing tools support. These findings demonstrate that protein language models capture distinct signals relevant for nucleotide-level coding sequence detection, especially at very short lengths. Ultimately, DeepCDS may help uncover the functional potential of the vast microbial diversity that remains genomically uncharacterized.

13.
arXiv (CS.CL) 2026-06-11

Goal-Autopilot: A Verifiable Anti-Fabrication Firewall for Unattended Long-Horizon Agents

作者:

Long-horizon LLM agents are not trusted to run unattended: with no human watching, they confidently report success they never verified. We treat honesty – bounding what an agent may claim at termination – as a first-class metric for unattended autonomy, distinct from capability. We present Autopilot, an execution model that makes silent fabricated success structurally impossible rather than merely rarer. Autopilot externalizes all working state into a durable, gated finite-state machine that a scheduler advances one stateless tick at a time; a hard floor forbids any terminal "done" claim whose falsifiable gate did not actually execute and pass. We prove a No-False-Success theorem – under gate soundness, floor enforcement, and plan coverage, termination implies the goal holds – whose only trust points are empirically measurable, and show the worst case degrades to an honest stall, never a fabricated success. Because each tick rehydrates only the state machine, per-step context cost is constant in the horizon. Across a 3,150-cell paired corpus (70 tasks $\times$ 3 systems $\times$ 3 models $\times$ 5 seeds, including 50 SWE-bench Lite tasks across 11 OSS repos), Autopilot fabricates on 0.95% of cells [95% CI 0.38–1.62] while Reflexion and StateFlow baselines fabricate on 8.10% [6.48–9.81] and 25.05% [22.48–27.62] respectively. The headline contrast lives in the hard regime: on SWE-bench Lite, the firewall reduces fabrication from 33.7% (StateFlow) to 0.67%, a paired difference of $-33.07$ pp [95% CI $-36.53, -29.73$]. The mechanism is the gate, not the model: all ten Autopilot fabrications come from the strongest model, while two weaker mid-tier models never fabricate across 700 paired cells. The firewall trades coverage for honesty by design – an honest stall is recoverable; a confident wrong output shipped downstream is not.

14.
arXiv (CS.AI) 2026-06-19

Protein Representation Learning with Secondary-Structure and Energy-Filtered Hydrogen-Bond Graphs

arXiv:2606.19374v1 Announce Type: cross Abstract: Graph-based representations are widely used in protein modeling, yet many existing approaches rely primarily on sequence adjacency or geometric proximity, which only partially reflect the principles governing protein folding. Proteins instead adopt complex three-dimensional conformations organized around secondary structure elements, such as $\alpha$-helices and $\beta$-sheets, which encode recurring local motifs and stabilizing hydrogen-bond interactions. In this work, we introduce a secondary-structure-aware graph neural network for protein representation learning. Residue-level node representations are augmented with secondary structure assignments, and graph edges are constructed from hydrogen-bond interactions filtered by their energetic strength. This design enables the model to capture both local structural context and long-range couplings that are central to protein stability and function. We evaluate the proposed approach on commonly used protein benchmarks and observe consistent improvements over existing graph-based methods. In addition, the resulting graph representations offer enhanced biological interpretability, as the learned connectivity aligns with established structural motifs. These findings suggest that incorporating secondary structure and energy-filtered hydrogen-bond topology provides an effective inductive bias for protein representation learning. The code is released at https://github.com/mohamedmohamed2021/SSProNet

15.
Nature (Science) 2026-06-17

Towards Conversational AI for Disease Management

While large language models (LLMs) have shown promise in diagnostic dialogue1, their capabilities for effective management reasoning—including disease progression, therapeutic response, and safe medication prescription—remain under-explored. We advance the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE)1−3 through a new LLM-based agentic system optimized for multi-visit clinical management and dialogue. To ground its reasoning in authoritative clinical knowledge, AMIE leverages Gemini’s long-context capabilities4, combining in-context retrieval with structured reasoning to align its output with up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multi-visit case scenarios designed to reflect UK NICE Guidance and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning as assessed by specialists and scored better in both preciseness of treatments and investigations, and in its alignment with and grounding in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark derived from two national drug formularies (US, UK) and validated by board-certified pharmacists. Though AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher difficulty questions. While further research would be needed before real-world translation, AMIE’s strong performance across evaluations marks a significant step towards conversational AI as a tool in disease management.

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

Smoothing Dark Areas in Molecular Latent Diffusion

arXiv:2606.13955v1 Announce Type: new Abstract: Latent diffusion is a promising framework for scalable 3D molecular generation, but it requires a latent space that remains smooth, valid, and navigable beyond posterior samples. Existing molecular VAEs, however, are typically learned through reconstruction-based objectives, which do not guarantee such a latent space. We show that this leads to dark areas: regions of latent space that are reachable during diffusion sampling but decode to disconnected or chemically invalid molecules. Unlike in image generation, molecular decoding requires strict structural and chemical precision, so even small latent perturbations can produce catastrophic failures. We therefore propose TopVAE, a topology-optimized VAE that reduces dark areas by making the decoder internalize structural and chemical constraints during training, eliminating the need for test-time chemical correction. TopVAE greatly improves off-posterior robustness, and when paired with a standard DiT, achieves $77\%$ lower FCD-3D on QM9, the highest V&C, $52\%$ lower FCD-3D on GEOM-Drugs, and $1.29{\times}$ more stable and connected molecules on zero-shot scaffold inpainting.

17.
arXiv (CS.LG) 2026-06-17

Physics-Constrained Neural Networks for Improved Short-Term Weather Forecasting: A Case Study over the South Pacific

arXiv:2606.17659v1 Announce Type: new Abstract: This study introduces enhancements to physics-constrained neural networks (PCNNs) that improve the accuracy and stability of hybrid short-term weather forecasting models. Building on the WeatherGFT architecture, three innovations are proposed. First, an upgraded numerical solver, combining a fifth-order weighted essentially non-oscillatory scheme (WENO-5), a beta-plane approximation, and subgrid-scale viscosity, permits a fourfold increase in the integration time step to 1200 s while reducing the daily mean squared error by up to 26%. Second, a unified autoregressive hybrid block replaces the original chain of 24 specialised modules, eliminating overfitting to specific lead times. Third, the physical core is integrated with two state-of-the-art neural backbones, resulting in PI-PredFormer and PI-IAM4VP. Evaluation on the WeatherBench South Pacific subset from 2000 to 2004 shows that these hybrids reduce root mean squared error at 1-12 h lead times by 8-22% compared to purely neural counterparts, while better preserving physical consistency. These results demonstrate that incremental refinement of hybrid components offers a practical route toward more accurate and efficient short-range weather forecasting.

18.
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.

19.
arXiv (CS.AI) 2026-06-12

Contextual Invertible World Models: A Neuro-Symbolic Agentic Framework for Colorectal Cancer Drug Response

arXiv:2603.02274v3 Announce Type: replace-cross Abstract: Precision oncology is currently limited by the small-N, large-P paradox, where high-dimensional genomic data is abundant but pharmacological response samples are sparse. While deep learning achieves predictive accuracy, it frequently fails to provide the mechanistic clarity required for clinical adoption. We present the Contextual Invertible World Model (CIWM), a Neuro-Symbolic Agentic Framework that bridges this gap by integrating a quantitative machine learning emulator with a Large Language Model reasoning layer. Utilising a stringently curated, high-fidelity data engineering pipeline on the Sanger GDSC dataset (\( N=83 \)), we isolate true biological signals from in vitro artifacts to establish a rigorous baseline predictive correlation for complex transcriptomics (\( r=0.268 \)). Through Inverse Reasoning, we perform in silico CRISPR perturbations across the colorectal landscape. The framework autonomously overturns classical mechanistic assumptions, identifying a hierarchical dominance of mutant KRAS over the APC/Wnt-axis in driving 5-fluorouracil resistance (\( \Delta=-0.0469 \)) via a "KRAS Shield" mapped to MAPK/PI3K networks. Furthermore, the agentic layer identified a "PIK3CA Paradox", revealing that repairing PIK3CA inadvertently increases chemoresistance (\( \Delta=+0.0085 \)) by triggering a compensatory feedback loop that hyperactivates the dominant MAPK survival pathway.

20.
arXiv (CS.CV) 2026-06-18

The Market in the Model: Latent Diffusion as Neural Economy

Valuable critique of generative image models within visual culture and the humanities has emphasized the role of datasets in shaping the images they produce. Yet, close studies of the ideological positions embedded into the mechanism of the models have been neglected, leaving them imagined as "black boxes." In a bid to expand, rather than replace, dataset critique, this paper examines the mechanisms of the latent diffusion model in terms of the problems they were brought in to solve on behalf of computer vision engineers, and the decisions each component was tasked with automating. I interpret that ensemble through the histories of its parts and the theory of vision the system inscribes into every generated image. Drawing on Impett and Offert's notion of neural exchange value, I offer this analysis to argue that the model operates as a neural economy: a contained symbolic system that abstracts social communication into commensurable vectors as it transfers the social sphere into parcels for sale. Tracing the training and generation pipelines component by component reveals what each operation displaces, and how it further entrenches the logics of platform and attention economies over social communication. The paper warns that any critique fixated exclusively on copyright and commodity defenses risks reaffirming the very fetishism the model produces, and argues instead for centering social exchange.

21.
arXiv (CS.CV) 2026-06-19

VisDom: Sparse Novel View Synthesis with Visible Domain Constraint

Sparse novel view synthesis (NVS) remains challenging due to the ambiguity of recovering 3D geometry from few input views. While NeRF- and Gaussian Splatting (GS)-based methods perform well with dense supervision, they often overfit in sparse settings, producing floating artifacts and inconsistent geometry. Silhouette consistency is commonly used as a regularizer, but it remains insufficient, as silhouette-consistent regions can extend beyond the true object geometry. We introduce VisDom, a learning-free geometric constraint that augments classical carving-based visual hull reconstruction by enforcing a minimum multi-view visibility requirement. Specifically, we define a visible domain as the subset of 3D space observed by at least $K$ views and use it as an additional filtering criterion on top of standard silhouette-based reconstruction. This provides a stronger spatial prior in sparse-view settings. We integrate VisDom into both implicit (NeRF) and explicit (GS) pipelines by restricting volumetric sampling and guiding Gaussian placement during optimization. Experiments on three challenging datasets show consistent improvements in sparse-view NVS, enabling high-quality object-centric reconstruction from as few as four input images. Our method is domain-agnostic, requires only silhouettes, and introduces no learned parameters, making it a simple complement to existing approaches. Applying VisDom on top of GaussianObject further improves performance on Omni3D and MipNeRF360, while matching or surpassing it at 22 $\times$ lower training cost.

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

Improving Detection of Rare Nodes in Hierarchical Multi-Label Learning

arXiv:2602.08986v2 Announce Type: replace-cross Abstract: In hierarchical multi-label classification, a persistent challenge is enabling model predictions to reach deeper levels of the hierarchy for more detailed or fine-grained classifications. This difficulty partly arises from the natural rarity of certain classes (or hierarchical nodes) and the hierarchical constraint that ensures child nodes are almost always less frequent than their parents. To address this, we propose a weighted loss objective for neural networks that combines node-wise imbalance weighting with focal weighting components, the latter leveraging modern quantification of ensemble uncertainties. By emphasizing rare nodes rather than rare observations (data points), and focusing on uncertain nodes for each model output distribution during training, we observe improvements in recall by up to a factor of five on benchmark datasets, along with statistically significant gains in $F_{1}$ score. We also show our approach aids convolutional networks on challenging tasks, as in situations with suboptimal encoders or limited data.

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

Why SWAVE May Not Be All You Need:A Concept-Evolution Retrospective on Complex-Valued Recurrent Language Models

arXiv:2606.18324v1 Announce Type: cross Abstract: SWave is a complex-valued recurrent language model (169.26M parameters, D=384, L=16, T=2048) trained on FineWeb-Edu using 2xH100 NVL. It was designed around three founding premises: that representing language as complex waves rather than real-valued numbers enables richer information encoding; that a Cayley-parameterised unitary transition provides a mathematical guarantee against state decay or explosion; and that a hidden state which rotates rather than shrinks preserves signal integrity over arbitrarily long contexts. The core of SWave evolved substantially across three development phases. The Resonance Head was found to structurally admit imaginary-channel collapse as a global loss minimum (a failure mode we term cos-domination collapse) and was superseded by an untied head with independent real and imaginary embedding tables from the Phase-Associative Memory (PAM) architecture. This resolved the degenerate minimum and enabled stable 200,000-step training (best-step PPL 22.0 at step 89,861). ComplexNorm and the Wave Propagation Scan proved load-bearing throughout all three phases and were retained to the final architecture. ProtectGatedScan was reframed as a structural prior rather than a learned behaviour. The four multi-scale retention concepts showed no measurable improvement under controlled evaluation and were found non-load-bearing. The ComplexGatedUnit was superseded by a real-valued squared-ReLU channel mixer with fewer parameters. The auxiliary training objectives showed no benefit once structural constraints were resolved. The investigation yields a formal characterisation of cos-domination collapse, a parallel scan with a log-space backward pass for numerical stability, six transferable engineering principles for complex-valued recurrent training, and a plan-to-code traceability methodology for catching structural divergences that conventional test suites miss.

24.
arXiv (CS.CV) 2026-06-17

Phenotyping TPF via Self-Supervised Learning: A Label-Agnostic Framework with Expert Validation

The full potential of artificial intelligence in tibial plateau fracture characterisation remains unrealised, constrained by a fundamental dependency on labelled datasets whose consistency cannot be guaranteed: conventional classification schemes such as Schatzker and AO/OTA suffer from inter-observer variability, causing supervised models to learn human disagreement rather than stable fracture morphology. We design, implement, and validate a label-agnostic framework that eliminates this constraint by learning fracture representations directly from imaging data without observer-assigned labels. A RadImageNet-pretrained ResNet-50 encoder is fine-tuned on 154 cleaned knee radiographs using the SimCLR contrastive objective, preceded by a data cleaning protocol and followed by UMAP dimensionality reduction and k-means clustering to discover four imaging-derived phenotypes. Phenotype validity is assessed through a blinded expert review protocol administered to two independent clinicians. The four phenotypes demonstrate robust stability (bootstrap ARI = 0.319 +/- 0.041), strong internal cohesion (silhouette = 0.511), and coherence ratings of 3-5/5 from both reviewers under blinded conditions; one phenotype was unanimously identified as exhibiting comminution – a high-complexity feature isolated without any supervisory signal. Inter-partition comparison against Schatzker labels yields ARI = 0.013, confirming orthogonality to conventional classification boundaries. Notably, expert reviewers anchored to established classification vocabularies perceived imaging-derived groups as heterogeneous precisely where Schatzker alignment was lowest, suggesting that Schatzker-trained perception and label-agnostic embedding geometry measure orthogonal dimensions. These findings establish label-agnostic SSL phenotyping as a reproducible and clinically interpretable complement to conventional classification.

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arXiv (CS.CV) 2026-06-17

MagicSim: A Unified Infrastructure for Executable Embodied Interaction

Robot learning and embodied agents now require simulation to serve as a shared execution substrate linking control, skills, and planning, not only as a renderer, controller testbed, or fixed task environment. Existing pipelines split these layers with "magic" actions, disconnected training environments, or forward-only renders that cannot reproduce, evaluate, and annotate the same episode. We present MagicSim, an embodied interaction infrastructure built around one deterministic batched runtime and a shared Markov decision process (MDP). From YAML-first specifications that decouple contents, placement, behavior, and agent exposure, MagicSim constructs diverse executable worlds spanning task families, interaction regimes, physics, layouts, sensors, avatars, and robot embodiments in one reset-and-step loop. A common execution interface grounds high-level commands through controllers, atomicskills, planner primitives, and asynchronous planning, realizing them as robot actions rather than simulator-side state edits. One task definition supports three capabilities: benchmark and RL evaluation, an autocollect interface that automatically turns commands into grounded trajectories, and agent/VLM-facing interaction. For automatic execution, commands flow through a Command->Skill->Planner->Robot->Record pipeline, while per-environment command, skill, planning, retry, annotation, and episode states advance independently above the shared physics tick. Successful rollouts are saved as structured multimodal trajectories aligning language supervision, action representations, visual/geometric representations, and task-level status with the executed episode. MagicSim thus unifies diverse world construction, embodied execution, task evaluation, automatic rollout generation, and interactive agent interfaces in one planner-in-the-loop runtime.