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

FutureOmni: Evaluating Future Forecasting from Omni-Modal Context for Multimodal LLMs

Although Multimodal Large Language Models (MLLMs) demonstrate strong omni-modal perception, their ability to forecast future events from audio-visual cues remains largely unexplored, as existing benchmarks focus mainly on retrospective understanding. To bridge this gap, we introduce FutureOmni, the first benchmark designed to evaluate omni-modal future forecasting from audio-visual environments. The evaluated models are required to perform cross-modal causal and temporal reasoning, as well as effectively leverage internal knowledge to predict future events. FutureOmni is constructed via a scalable LLM-assisted, human-in-the-loop pipeline and contains 919 videos and 1,034 multiple-choice QA pairs across 8 primary domains. Evaluations on 13 omni-modal and 7 video-only models show that current systems struggle with audio-visual future prediction, particularly in speech-heavy scenarios, with the best accuracy of 64.8% achieved by Gemini 3 Flash. To mitigate this limitation, we curate a 7K-sample instruction-tuning dataset and propose an Omni-Modal Future Forecasting (OFF) training strategy. Evaluations on FutureOmni and popular audio-visual and video-only benchmarks demonstrate that OFF enhances future forecasting and generalization. We publicly release all code (https://github.com/OpenMOSS/FutureOmni) and datasets (https://huggingface.co/datasets/OpenMOSS-Team/FutureOmni).

02.
arXiv (CS.CL) 2026-06-17

When English Isn't the Best Teacher: Source Language Effects in Cross-Lingual In-Context Learning

Cross-lingual transfer in multilingual NLP has been widely explored in supervised fine-tuning contexts, where factors like data availability and linguistic similarity largely determine transfer quality. As the field shifts toward few-shot In-Context Learning (ICL), it is often presumed that insights from fine-tuning carry over unchanged. Yet this assumption has not been rigorously evaluated, leaving open the question of how to choose source languages for cross-lingual ICL. We conduct a broad empirical study of cross-lingual transfer in ICL spanning seven tasks, six models, and a typologically diverse set of languages. We further analyze language confusion, a key obstacle for generative tasks in cross-lingual ICL. Our results show that conventional fine-tuning-based expectations do not consistently apply in the ICL regime and point to alternative heuristics for selecting source languages effectively.

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

Toward Accessible Psychotherapy Training Using AI-Driven Interactive Patient Avatars

Training psychotherapists in evidence-based interventions such as Acceptance and Commitment Therapy (ACT) requires repeated practice with meaningful feedback, yet opportunities for safe, standardized training are limited by ethical, logistical, and resource constraints. We introduce a system designed to support ACT-oriented psychotherapy training through spoken dialogue with an embodied virtual patient. The system uses large language models to simulate patient behavior conditioned on profiles derived from real therapy sessions and configurable clinical scenarios, while a separate automated evaluator provides turn-by-turn feedback on therapist responses based on established ACT fidelity criteria. Rather than aiming to replace supervision, the system is intended to support deliberate practice by enabling experimentation, reflection, and immediate feedback in low-risk settings. Expert evaluation with practicing psychologists confirmed high realism in patient behavior and demonstrated that immediate turn-by-turn ACT feedback increased therapists' awareness of intervention choices and enabled effective experimentation with alternative responses. Quantitative evaluation across 49 therapy transcripts identified GPT-4o-mini as the optimal feedback model, achieving the lowest mean absolute error (MAE = 6.12) in replicating human supervisor ACT fidelity ratings with statistically significant agreement. This work demonstrates the potential of fidelity-aware simulated patients as a scalable complement to psychotherapy training.

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

Bridging Modal Isolation in Interleaved Thinking: Supervising Modality Transitions via Stepwise Reinforcement

Interleaved thinking, where a unified multimodal model alternates between textual reasoning and visual generation, has shown promise on spatial and physical tasks. However, in complex long-chain scenarios, we identify a fundamental failure mode: generated images diverge from the textual context while subsequent text ignores the visual evidence, causing the two modalities to alternate without genuinely informing each other. We term this Modal Isolation and attribute it to compounding information loss at modality boundaries. We decompose each reasoning cycle into atomic operations and define modality transition loss, quantifying cross-modal hallucination (text-to-image) and visual utilization deficit (image-to-text) at each boundary. We propose MoTiF (Modality Tiransition Fidelity), a two-stage training framework that directly optimizes these transitions: Reflective SFT trains the model to detect and recover from erroneous visual outputs; Flow-GRPO improves image generation fidelity via reinforcement learning. All training signals in MoTiF derive from transition-level fidelity rather than end-task accuracy. Across four visual puzzle benchmarks, this transition-level supervision substantially improves both cross-modal coherence and final task accuracy. The results demonstrate that effective interleaved reasoning requires explicit structural supervision at modality boundaries, not merely scaling or end-task optimization.

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

GroupToM-Bench: Benchmarking Group Theory of Mind and Nonlinear Social Emergence in MLLMs

True general intelligence requires not only a model of the physical world but also a social world model: the capacity to infer how individual mental states interact and crystallize into group-level outcomes. Despite notable progress in individual-level Theory of Mind (ToM) reasoning, existing multimodal large language models fail at this broader task. Collective behavior emerges non-linearly from social tensions, conformity dynamics, and structural constraints, meaning it cannot be recovered by merely summing individual intentions. We present GroupToM-Bench, the first multimodal benchmark for group-level ToM, built around a causal chain spanning micro-level BDI states (belief, desire, intention), meso-level group tension and structural constraints, and macro-level outcome prediction and mechanistic attribution. To probe this full arc, we develop a seven-level cognitive audit framework. Experiments reveal a gap between current models and human baselines, highlighting a failure to process social structures and non-linear collective dynamics.

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

A Mathematical Theory of Value: a synthesis on goal-directed agency under resource constraints

作者:

arXiv:2606.12502v1 Announce Type: cross Abstract: We propose that value – the quantity goal-directed agents create, destroy, and exchange – is a lawful structural quantity in the same category as information. Following Shannon's method, we make one ruthless abstraction: value is the rate at which an agent converts a resource into goal-progress, relative to a frame fixed by its goal. A scale-invariance axiom forces a logarithmic measure, $V=\sum_i k_i \ln e_i$; compounding of a reinvested resource forces the same form via the ergodicity argument of Peters (2019). The two routes are kin rather than independent; their agreement is a consistency check, not an over-determination. We derive a coding theorem of value: $\Delta G \le I(X;Y)$, achieved by Bayes-proportional allocation; realized value decomposes as $G=D(q\|r)-D(q\|p)$, identifying misalignment with measurable waste. For populations, value is frame-relative while price is frame-independent; a fleet that pools its resource and fuses its perception inherits the ceiling $G_{\mathrm{fleet}} \le I(X;Y_{1:m}) \le H(X)$ (a corollary; an earlier sum-form claim was wrong and is corrected in v5). A dynamical layer yields an is/ought asymmetry from which alignment emerges as a control-stability condition with a closed-form residual. We test the single-frame laws on live language models in a pre-registered scale-up: perception mutual information tracks realized capability rather than parameter count (Spearman $\rho = 0.977$ pooled over 30 model$\times$domain points), out-of-sample $\Delta G$ tracks $I(X;Y)$, and over-confidence is measurable dissipation; a further pre-registered test shows the bridge is shape-invariant across four task shapes ($n=42$, slope 0.953). None of the mechanisms is individually new – generalized Kelly, Armstrong & Mindermann (2018), classical control; the contribution is their unification and the governance mapping (incentive design over oversight) that follows.

07.
arXiv (CS.CL) 2026-06-16

Weaving Multi-Source Evidence for Biomedical Reasoning: The BioMedHop Benchmark and BioWeave Framework

Biomedical question answering (QA) increasingly requires reasoning over interacting entities, where supporting evidence is scattered across biomedical knowledge graphs, literature documents, and web-accessible resources. However, existing biomedical QA benchmarks mainly focus on exam-style knowledge, literature comprehension, or short-range multi-hop inference, leaving source-conditioned graph reasoning and evidence topology construction underexplored. To fill this gap, we introduce BioMedHop, a multi-source graph-grounded benchmark for evaluating biomedical reasoning over structured evidence topologies. BioMedHop contains 10,045 instances across KG, document, web, and hybrid evidence settings, covering shared-neighbor matching, intersection reasoning, path-based reasoning, and counting, with option-based, open-ended, and numeric count renderings. To support this benchmark, we further propose BioWeave, a source-aware reasoning framework that retrieves biomedical KG paths, gathers supporting clues from documents and web sources, assembles them into a unified evidence graph, and verifies answers through entity-level evidence support. Comprehensive experiments show that BioWeave achieves the best overall performance among compared methods on BioMedHop, outperforming the strong hybrid baseline ToG-2 by 10.5% in the overall average. Moreover, BioWeave consistently improves different LLM backbones and enables smaller models, such as Qwen3-4B, to achieve reasoning performance comparable to GPT-4-Turbo.

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

Robust State-Conditional Feature-Weighted Jump Models for Temporal Clustering

arXiv:2606.13146v1 Announce Type: cross Abstract: We propose a robust feature-weighted jump model for time-dependent clustering. A penalty is used to encourage smoothness of transitions over time, while robustness is achieved through the use of a Tukey's biweight loss function. An additional parameter controls the variability of feature weights across states, allowing the model to assign state-specific relevance to each feature. We illustrate in simulation how the method accurately recovers the true cluster sequence and reliably identifies relevant features, outperforming competing approaches, particularly in the presence of outliers. We conclude with two empirical applications, one on the number of conflict-related homicides in Kosovo in the period 1998-2000, and another on macroeconomic performance of twelve European countries in the period 1949-2024.

09.
arXiv (quant-ph) 2026-06-17

Tunneling Dynamics and Time Delay in Electron Transport through Time-Dependent Barriers with Finite-Bandwidth Reservoirs

arXiv:2507.20649v2 Announce Type: replace-cross Abstract: We study a model system consisting of a tunneling barrier driven by an external harmonic field and coupled to two leads with finite bandwidth. Avoiding Floquet expansions, we derive simple expressions for the time-dependent tunneling current in the adiabatic regime. Our approach relates the barrier modulation to a measurable time delay in the steady-state periodic current. It provides a physically consistent definition of the tunneling time inside the barrier by subtracting the time delay associated with the leads from the total time delay. We find that the tunneling time always vanishes for wide/high barriers. Remarkably, the time delay persists even when the barrier becomes static, i.e., in the limit where the modulation frequency vanishes. This indicates that the time delay obtained through the introduction of an external periodic perturbation actually reflects an intrinsic property of the tunneling dynamics, rather than an effect of the external drive or of a particular system. We apply our results to the analysis of tunneling times in optical experiments and find good agreement with the experimental data.

10.
medRxiv (Medicine) 2026-06-18

Looked but didn't see: inattentional blindness and yes-bias confabulation in vision-language models

Previous work showed that many participants fail to notice a gorilla in a video of people playing basketball. Another study found that 83% of trained radiologists failed to report a gorilla figure inserted into a chest CT nodule-search task, even though eye-tracking revealed that most observers had foveated the figure. We ask whether a similar phenomenon exists in contemporary vision-language models (VLMs). We find that (i) VLMs are capable of spotting the gorilla in both still-frame images and videos of lung CT scans; (ii) models display inattentional blindness, which varies according to model generation and type of stimulus presented; (iii) Gemini-3.1-Pro outperforms most other flagship and open-weight VLMs at identifying the presence or absence of the gorilla. We additionally ran a segmentation experiment utilizing two different model classes: a generalist (SAM 3), which found the gorilla but produced little to no results for anatomy-based prompts; a medical specialist (BiomedParse), which produced more promising anatomy-based results but flagged "gorilla" on gorilla-free control videos on 82% of frames. The behavioral signature of inattentional blindness reproduces in VLMs, but a unique confabulation failure mode means that any "did the model see X" claim requires signal-detection analysis with a matched-control false-alarm baseline.

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

Robust Fall Recovery for Armless Bipedal-Wheeled Robots Via Force-Guided Learning

arXiv:2606.14270v1 Announce Type: cross Abstract: Fall recovery is critical for autonomous legged locomotion. Existing methods have demonstrated that some legged robots, such as humanoids and quadrupeds, are capable of fall recovery from diverse postures by utilizing arms or coordinating multi-legs to generate support forces. Without arms or other legs to provide supportive assistance, a bipedal-wheeled robot must rely solely on the actuation of its legs, making recovery particularly difficult. To address this, we introduce FTSR (Force-guided Teacher-student framework with Stage-wise Rewards). The force-guided method constructs an external auxiliary force during simulation training that correlates directly with the robot's real-time height, explicitly formulating this force as an optimizable constraint. Through constrained reinforcement learning, the policy is guided toward reducing force dependency gradually and increasing the body height, developing internal recovery strategies despite having no arms for support. Height-progressive stage-Wise rewards progressively structure posture stabilization during recovery and transition to sustained locomotion, integrated with teacher-student architecture distilling privileged knowledge of force effects and recovery dynamics. After simulation training, the policy is deployed on a physical armless bipedal-wheeled robot and extensively evaluated. Experiments confirm robust and reliable fall recovery under diverse challenging conditions, demonstrating strong environmental adaptability and motion robustness, while maintaining full post-recovery motion capability. The framework also generalizes effectively to a high-DOF humanoid, confirming its practical generalizability. The project page is available at https://2350575870.github.io/force-guided.github.io/

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

Learning and Generating Mixed States Prepared by Shallow Channel Circuits

arXiv:2604.01197v4 Announce Type: replace-cross Abstract: Learning quantum states from measurement data is a central problem in quantum information and computational complexity. In this work, we study the problem of learning to generate mixed states on a finite-dimensional lattice. Motivated by recent developments in mixed state phases of matter, we focus on arbitrary states in the trivial phase. A state belongs to the trivial phase if there exists a shallow preparation channel circuit under which local reversibility is preserved throughout the preparation. We prove that any mixed state in this class can be efficiently learned from measurement access alone. Specifically, given copies of an unknown trivial phase mixed state, our algorithm outputs a shallow local channel circuit that approximately generates this state in trace distance. The sample complexity and runtime are polynomial (or quasi-polynomial) in the number of qubits, assuming constant (or polylogarithmic) circuit depth and gate locality. Importantly, the learner is not given the original preparation circuit and relies only on its existence. Our results provide a structural foundation for quantum generative models based on shallow channel circuits. In the classical limit, our framework also inspires an efficient algorithm for classical diffusion models using only a polynomial overhead of training and generation.

13.
arXiv (CS.AI) 2026-06-19

PrototypeNAS: Rapid Design of Deep Neural Networks for Microcontroller Units

arXiv:2603.15106v2 Announce Type: replace Abstract: Enabling efficient deep neural network (DNN) inference on edge devices with different hardware constraints is a challenging task that typically requires DNN architectures to be specialized for each device separately. To avoid the huge manual effort, one can use neural architecture search (NAS). However, many existing NAS methods are resource-intensive and time-consuming because they require the training of many different DNNs from scratch. Furthermore, they do not take the resource constraints of the target system into account. To address these shortcomings, we propose PrototypeNAS, a zero-shot NAS method to accelerate and automate the selection, compression, and specialization of DNNs to different target microcontroller units (MCUs). We propose a novel three-step search method that decouples DNN design and specialization from DNN training for a given target platform. First, we present a novel search space that not only cuts out smaller DNNs from a single large architecture, but instead combines the structural optimization of multiple architecture types, as well as optimization of their pruning and quantization configurations. Second, we explore the use of an ensemble of zero-shot proxies during optimization instead of a single one. Third, we propose the use of Hypervolume subset selection to distill DNN architectures from the Pareto front of the multi-objective optimization that represent the most meaningful tradeoffs between accuracy and FLOPs. We evaluate the effectiveness of PrototypeNAS on 12 different datasets in three different tasks: image classification, time series classification, and object detection. Our results demonstrate that PrototypeNAS is able to identify DNN models within minutes that are small enough to be deployed on off-the-shelf MCUs and still achieve accuracies comparable to the performance of large DNN models.

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

Bid Farewell to Seesaw: Towards Accurate Long-tail Session-based Recommendation via Dual Constraints of Hybrid Intents

arXiv:2511.08378v4 Announce Type: replace-cross Abstract: Session-based recommendation (SBR) aims to predict anonymous users' next interaction based on their interaction sessions. In the practical recommendation scenario, low-exposure items constitute the majority of interactions, creating a long-tail distribution that severely compromises recommendation diversity. Existing approaches attempt to address this issue by promoting tail items but incur accuracy degradation, exhibiting a "see-saw" effect between long-tail and accuracy performance. We attribute such conflict to session-irrelevant noise within the tail items, which existing long-tail approaches fail to identify and constrain effectively. To resolve this fundamental conflict, we propose HID (Hybrid Intent-based Dual Constraint Framework), a plug-and-play framework that transforms the conventional "see-saw" into "win-win" through introducing the hybrid intent-based dual constraints for both long-tail and accuracy. Two key innovations are incorporated in this framework: (i) Hybrid Intent Learning, where we reformulate the intent extraction strategies by employing attribute-aware spectral clustering to reconstruct the item-to-intent mapping. Furthermore, discrimination of session-irrelevant noise is achieved through the assignment of the target and noise intents to each session. (ii) Intent Constraint Loss, which incorporates two novel constraint paradigms regarding the diversity and accuracy to regulate the representation learning process of both items and sessions. These two objectives are unified into a single training loss through rigorous theoretical derivation. Extensive experiments across multiple SBR models and datasets demonstrate that HID can enhance both long-tail performance and recommendation accuracy, establishing new state-of-the-art performance in long-tail recommender systems.

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

Attention-Based Prototype Calibration for Multi-Rater Few-Shot Medical Image Segmentation

Few-shot medical image segmentation methods typically assume a single ground-truth annotation, overlooking systematic variability across expert raters commonly observed in clinical datasets. We propose an attention-based prototype calibration framework for few-shot multi-rater segmentation that models rater-specific deviations from a consensus representation in prototype space. A lightweight yet principled attention operator directly refines rater prototypes without modifying the backbone feature extractor, making the approach fully compatible with existing prototype-based few-shot segmentation methods. This design preserves semantic consistency while enabling personalized segmentation outputs with minimal computational overhead. Experiments on multi-rater medical imaging datasets demonstrate consistent improvements over baseline prototype approaches, highlighting the effectiveness of structured prototype calibration for modeling annotation variability. Our code is available at https://github.com/truong2710-cyber/JAPC.

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

Critically Engaged Pragmatism: Scientific Norm and Social, Pragmatist Epistemology for AI Science Evaluation Tools

arXiv:2601.09753v2 Announce Type: replace-cross Abstract: AI science evaluation tools aim to assess research credibility. As with traditional metrics such as impact factors, their edicts can be decontextualised and repurposed in problematic ways. To address this, I propose Critically-Engaged Pragmatism as a scientific norm enjoining scientific communities to scrutinise the purposes and purpose-specific reliability of AI science evaluation tools. To foster Critically Engaged Pragmatism, creators of AI science evaluation tools should transparently and fully report design, training, and benchmarking details to facilitate assessments of purpose-specific reliability, liability to different types of error, and bias. What count as best practices for the transparent reporting of AI science evaluation tools should be updated as new forms of error, bias, and gamesmanship are discovered. Under this framework, AI science evaluation tools are not objective arbiters of scientific credibility. Rather, they are the object of critical discursive practices that ultimately ground the credibility of scientific communities.

17.
arXiv (CS.LG) 2026-06-15

Muon$^p$: Muon with Fractional Spectral Powers

arXiv:2606.13867v1 Announce Type: new Abstract: Muon is an increasingly widely used optimizer that replaces a gradient $G=USV^\top$ with its polar factor $UV^\top$, thereby flattening the singular spectrum. However, full flattening discards singular-value information that may matter for adaptation. We introduce Muon$^p$, a Muon-style optimizer that instead uses fractional spectral-power updates $US^pV^\top$ for rational $p\in(0,1)$, interpolating between Muon and gradient descent. To make it practical, we prove that fractional spectral powers cannot be computed by any fixed univariate polynomial iteration, and furthermore derive low-degree odd bivariate recurrences that approximate $US^pV^\top$ using only matrix multiplications, preserving Muon's matrix-multiplication-only structure and compute complexity. We show that Muon$^p$ maximizes the linear improvement in loss under the Schatten $q$-norm for $q=1+\frac{1}{p}$. Empirically, Muon$^p$ is especially effective for finetuning: on billion-scale models, Muon$^p$ improves validation perplexity and downstream task performance. We further analyze when Muon$^p$ is less suitable, through the lens of spectral geometry. Our results reveal important insights on when preserving the singular spectrum can bring significant gains, and introduce a principled way to achieve them.

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

Can AI Agents Synthesize Scientific Conclusions?

Scientific AI agents increasingly retrieve evidence, reason across sources, and synthesize conclusions used in consequential decisions. Yet, their ability to do so in high-stakes domains such as health remains unclear. We introduce SciConBench, a large-scale live benchmark of 9.11K questions and expert-written conclusions from systematic reviews to evaluate open-domain scientific conclusion synthesis. The benchmark draws on an expert-validated automated evaluation pipeline that decomposes conclusions into atomic facts and measures correctness and comprehensiveness via factual precision and recall. To mitigate data leakage, we further introduce SciConHarness, a clean-room evaluation harness that equips agents with controlled web interaction to ensure valid measurement. Evaluating 8 frontier models and deep research agents, we find that factual quality remains low: under clean-room settings, the best agent achieves only a factual F1 of 0.337. Our clean-room setting consistently reduces performance relative to unconstrained evaluation, suggesting that leakage inflates estimates of models' true synthesis capabilities. Finally, we audit consumer-facing agents (e.g., Google AI Overview, OpenEvidence) and find they frequently generate incomplete and sometimes contradictory conclusions, even when the ground-truth answer is available. Overall, our results show that reliable synthesis of scientific conclusions remains an open challenge, and that clean-room evaluation is essential for assessing open-domain AI agents.

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

Geometry of Lightning Self-Attention: Identifiability and Dimension

arXiv:2408.17221v3 Announce Type: replace Abstract: We consider function spaces defined by self-attention networks without normalization, and theoretically analyze their geometry. Since these networks are polynomial, we rely on tools from algebraic geometry. In particular, we study the identifiability of deep attention by providing a description of the generic fibers of the parametrization for an arbitrary number of layers and, as a consequence, compute the dimension of the function space. Additionally, for a single-layer model, we characterize the singular and boundary points. Finally, we formulate a conjectural extension of our results to normalized self-attention networks, prove it for a single layer, and numerically verify it in the deep case.

20.
arXiv (CS.CL) 2026-06-17

OpenLID-v3: Improving the Precision of Closely Related Language Identification – An Experience Report

Language identification (LID) is an essential step in building high-quality multilingual datasets from web data. Existing LID tools (such as OpenLID or GlotLID) often struggle to identify closely related languages and to distinguish valid natural language from noise, which contaminates language-specific subsets, especially for low-resource languages. In this work we extend the OpenLID classifier by adding more training data, merging problematic language variant clusters, and introducing a special label for marking noise. We call this extended system OpenLID-v3 and evaluate it against GlotLID on multiple benchmarks. During development, we focus on three groups of closely related languages (Bosnian, Croatian, and Serbian; Romance varieties of Northern Italy and Southern France; and Scandinavian languages) and contribute new evaluation datasets where existing ones are inadequate. We find that ensemble approaches improve precision but also substantially reduce coverage for low-resource languages. OpenLID-v3 is available on https://huggingface.co/HPLT/OpenLID-v3.

21.
medRxiv (Medicine) 2026-06-18

Development and Initial Validation of the Quality of life Evaluation in NF2-related Schwannomatosis Trials (QUEST) Assessment

Individuals with NF2-related schwannomatosis (NF2-SWN) experience a complex constellation of physical, emotional, and social symptoms that substantially impact quality of life (QoL). Although disease-specific patient-reported outcome measures are increasingly important for evaluating treatment benefit in clinical trials, existing NF2-SWN QoL measures have limitations in content coverage and sensitivity to change. This study describes the development and initial validation a new disease-specific QoL assessment – the Quality of Life Evaluation in NF2-related Schwannomatosis Trials (QUEST). Using a three-phase, mixed-methods approach, items were generated through concept elicitation interviews with individuals with NF2-SWN and clinicians, prioritized via patient survey data, and refined through iterative cognitive debriefing procedures. The resulting 21-item QUEST assesses the extent to which NF2-SWN has negatively impacted a persons daily life over the past seven days. Initial psychometric evaluation was conducted in an international sample of 174 individuals with NF2-SWN aged 15 years and older (117 women (67%), 158 White individuals (89%)). Exploratory factor analysis supported a four-factor structure, and the total score demonstrated excellent internal consistency and strong test-retest reliability. Evidence of construct validity was demonstrated through hypothesized associations with disease-specific, generic, and domain-specific QoL measures, as well as known-groups validity based on self-reported disease severity and number of prior surgeries. Incremental validity analyses indicated that QUEST explained unique variance beyond existing measures. Together, findings support the QUEST as a reliable and valid disease-specific QoL measure with strong content validity and feasibility for use as a clinical trial endpoint in NF2-SWN.

22.
bioRxiv (Bioinfo) 2026-06-15

Biological meaning in protein embedding space is resolution-dependent

Protein language model embeddings are increasingly used to organise biological sequences, yet how biological meaning is encoded within embedding neighbourhoods remains poorly understood. Using two independent hierarchical enzyme systems, carbohydrate-active enzymes and peptidases, we investigated how biological interpretation changes across embedding organisations aligned to different levels of biological hierarchy. Different embedding organisations give rise to distinct neighbourhood semantics. When aligned to membership-boundary resolution, embeddings robustly separated artefacts and unrelated proteins from members of the target category. However, embeddings aligned to functional-grouping resolution maintained compositional neighbourhood structure for multi-domain proteins spanning more than one functional or catalytic group. Finally, embeddings aligned to local-family resolution recovered compact family-like neighbourhoods, including families withheld from training, while weakening broader membership-boundary and functional-grouping relationships. Moreover, embeddings optimised toward the same level of biological organisation retain different biological relationships depending on optimisation trajectory employed. Together, our results show that proximity in protein embedding space has no fixed biological interpretation. Instead, biological meaning emerges across embedding resolutions through selective preservation of different forms of biological organisation.

23.
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.

24.
arXiv (math.PR) 2026-06-11

Consensus on Dynamic Stochastic Block Models: Fast Convergence and Phase Transitions

arXiv:2209.03999v2 Announce Type: replace Abstract: We introduce two models of consensus following a majority rule on time-evolving stochastic block models (SBM), in which the network evolution is Markovian or non-Markovian. Under the majority rule, in each round, each agent simultaneously updates their opinion according to the majority of their neighbors. Our network has a community structure and randomly evolves with time. In contrast to the classic setting, the dynamics is not purely deterministic, and reflects the structure of SBM by resampling the connections at each step, making agents with the same opinion more likely to connect than those with different opinions. In the Markovian model, connections between agents are resampled at each step according to the SBM law and each agent updates their opinion via the majority rule. We prove a power-of-one type result, i.e., any initial bias leads to a non-trivial advantage of winning in the end, uniformly in the size of the network. In the non-Markovian model, a connection between two agents is resampled according to the SBM law only when at least one of them changes opinion and is otherwise kept the same. We identify the phase-transition threshold, up to the second-order leading term, between halting and fast convergence to consensus. We also give sufficient initial-lead conditions for consensus to occur within one, two, or three rounds.

25.
medRxiv (Medicine) 2026-06-15

VarEx: A Large Language Model Pipeline for Automated Extraction of Exposures, Outcomes, and Covariates from Epidemiologic Studies

Objective: Observational studies are essential for investigating risk factors for Alzheimer's disease and related dementias (ADRD), but inconsistent reporting and selection of covariates can contribute to residual confounding, omitted-variable bias, and reduced reproducibility. We developed and evaluated VAREX (Variable Extraction), a large language model (LLM)-based information extraction framework designed to automatically identify exposures, outcomes, and covariates from epidemiologic studies and populate structured evidence repositories. Materials and Methods: VAREX combines retrieval-augmented generation, biomedical language-model embeddings, semantic chunking, cross-encoder reranking, and prompt-engineered LLM workflows to extract epidemiologic variables from full-text biomedical articles. The framework was evaluated using a reference-standard corpus of observational studies examining blood pressure variability (BPV) and Alzheimer's disease-related dementias (ADRD), together with external validation datasets involving other exposure-outcome relationships. Extracted variables were compared with independently curated human reference standards using semantic matching and one-to-one assignment procedures. Covariates were additionally classified into ten epidemiologically relevant semantic categories. Results: In the primary BPV[->]ADRD corpus (10 studies), VAREX achieved a precision of 0.91, recall of 0.84, and F1-score of 0.87 for variable extraction. Covariate classification accuracy was 0.90, yielding a strict extraction-and-classification F1-score of 0.78. External validation datasets demonstrated comparable performance across diverse epidemiologic domains, with extraction F1-scores ranging from 0.73 to 0.85. Category-level performance was strongest for health behaviors (F1=0.96), sociodemographic variables (F1=0.90), and medication exposures (F1=0.89). Compared with published estimates of manual systematic-review effort, VAREX reduced processing time from approximately 61 minutes to 9 minutes per article, representing an 85.7% reduction in review time. Discussion: These findings demonstrate that LLM-based information extraction can accurately identify and classify epidemiologic variables across heterogeneous observational-study designs. Automated extraction enables scalable construction of structured repositories of exposures, outcomes, and covariates while substantially reducing the labor required for evidence synthesis and systematic reviews. Conclusion: VAREX provides an effective framework for automated extraction and classification of epidemiologic variables from the biomedical literature. By supporting large-scale evidence synthesis and structured knowledge resource development, VAREX may facilitate more rigorous observational research, improved confounder identification, and enhanced reproducibility in epidemiology.