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01.
arXiv (CS.CV) 2026-06-15

NEST3D: A High-Resolution Multimodal Dataset of Sociable Weaver Tree Nests

Sociable weaver nests function as complex ecological structures offering thermoregulatory microhabitats and sustaining diverse species; however, datasets used in prior studies lack fine-grained 3D structural detail. Producing usable and accurate 3D weaver nest data is challenging due to their irregular geometry and integration with complex host vegetation. We bridge this gap with an open-access, 1.4 TB multimodal drone dataset of 104 nest-bearing trees, comprising 27,945 RGB images, 111,780 multispectral images, approximately 781 million 3D points, and expert-annotated semantic segmentation labels. We benchmark semantic segmentation using KPConv, RandLA-Net, and Point Transformer V3, with PT-v3 achieving an mIoU of 86.35% on the test set. While the results demonstrate strong performance for transformer-based and point-wise methods, they also highlight architecture-dependent challenges, particularly for convolution-based approaches such as KPConv. By uniquely combining spectral, spatial, and structural information, the presented dataset advances 3D reconstruction, segmentation, and classification algorithms, enabling ecological applications from nest volume estimation to species conservation, and serves as a demanding benchmark that exposes architecture-dependent performance under extreme class imbalance.

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

Tensor-based second-order causal discovery

arXiv:2606.18074v1 Announce Type: cross Abstract: Causal discovery seeks to uncover the causal dependencies among variables. For this purpose, we propose an algorithm called Tensor-based Second-order Causal Discovery (TSCD). Its input is a tensor obtained from the covariance matrices of observational and interventional data. Assuming the causal dependencies follow a linear structural equation model on a directed acyclic graph (DAG), TSCD outputs the DAG and the functions on its edges, requiring only that the noise variables are uncorrelated. We also implement a version of the approach for nonlinear models. Our focus on second-order statistics (via the covariance matrices) is motivated by their statistical and computational efficiency relative to higher-order moments, their identifiability relative to first-order statistics, and that they work regardless of whether the variables are Gaussian. We show that TSCD has identifiable causal order and parameters from a number of interventions that is logarithmic in the number of variables. Experiments show that TSCD is robust to noise, competitive with existing methods, and scales to hundreds of variables.

03.
arXiv (CS.CL) 2026-06-25

BitNet Text Embeddings

LLM-based text embedders have substantially improved retrieval and semantic representation quality, but their deployment remains costly: large backbone models slow down embedding inference, while high-dimensional full-precision embeddings impose substantial storage and bandwidth overhead on large-scale indexes. In this paper, we present BITEMBED, an extreme low-bit framework for LLM-based text embedding that jointly targets encoding efficiency and vector storage. BITEMBED converts pretrained LLM backbones into BitNet-style embedding encoders with ternary weights, quantized activations, and lightweight normalization refinement. The converted model is adapted to representation learning through continual contrastive pre-training, followed by supervised contrastive fine-tuning with both similarity-distribution distillation and attention-relation distillation from a full-precision teacher. Beyond quantizing the backbone, BITEMBED further trains output embeddings to support multiple storage precisions meeting different storage needs in various scenarios. Experiments on MMTEB (eng, v2) with Qwen3-0.6B and Gemma3-270M show that BITEMBED is largely comparable to full precision teacher embedders. Moreover, BITEMBED flexibly obtains text embeddings of various precisions, achieving a trade-off between performance and storage cost.

04.
arXiv (CS.CL) 2026-06-24

Progressive Alignment Objectives for Aligner-Encoder based ASR

Aligner-Encoders are recently proposed seq2seq end-to-end ASR models that replace decoder attention by predicting the uth token directly from the u-th encoder position, so the encoder must learn the alignment internally without cross-attention or a transducer lattice. In practice, this alignment often forms abruptly in the upper layers, making training sensitive and brittle on long utterances. We propose InterAligner, which adds an intermediate Aligner objective so alignment can form progressively across depth, together with an intermediate CTC loss (InterCTC) to stabilize optimization. On LibriSpeech with a 17-layer Conformer, a final-only Aligner reaches 5.0/7.8 WER (test-clean/other). InterCTC improves to 3.4/6.0, and InterAligner further reduces WER to 3.1/5.6 with the largest gains on long utterances.

05.
arXiv (quant-ph) 2026-06-15

Implementation of two-qubit Rydberg operations on neutral Rb-87 atoms in systems with different intermediate states

arXiv:2606.13975v1 Announce Type: new Abstract: This work presents an experimental setup for implementing two-qubit operations on neutral atoms ($^{87}$Rb) with the possibility of using two different Rydberg excitation schemes. One of them uses 5P$_{1/2}$ as the intermediate level and applies the second-stage beam locally to the addressed atoms. The second scheme uses the 6P$_{3/2}$ level; in this scheme, the particles to be entangled are moved to a separate zone through which both Rydberg beams pass. The advantages and limitations of both schemes are analyzed. Based on numerical modeling performed with a Julia package developed by the authors, it is demonstrated that the spatial configuration has a greater effect on quantum-operation fidelity than the choice of intermediate level. An experimental implementation of the scheme using the 6P$_{3/2}$ level is demonstrated, making it possible to achieve a two-qubit operation fidelity of 94%.

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

PromptShift-CRC: Drift-Aware Conformal Risk Control for Foundation Models Under Prompt and Domain Shift

arXiv:2606.15964v1 Announce Type: cross Abstract: Foundation models are now used in settings where the prompts they receive can change quickly. Users change, topics change, policies change, and the model may suddenly face a kind of request that was rare in the calibration data. This makes fixed calibration risky. Conformal prediction and conformal risk control give model-agnostic ways to control error, but they work best when the calibration data still look like the future data. This paper develops PromptShift CRC, a drift-aware conformal risk control method for foundation-model outputs under prompt and domain shift. The method embeds prompts and responses, measures how far the current prompt stream has moved from the calibration pool, gives more weight to relevant or recent calibration examples, and updates the risk level online after observed violations. It reports three practical diagnostics: realized risk error, prompt drift, and effective calibration size. We give conditions under which the method controls risk up to terms for distribution mismatch and weighted quantile uncertainty. In a synthetic prompt-shift benchmark, static conformal risk control fails sharply after drift, while PromptShift-CRC gives the best coverage among the adaptive baselines considered. We then evaluate the same calibration layer on public benchmark derived streams for question answering, toxicity, summarization factuality, and long-context hallucination risk

07.
bioRxiv (Bioinfo) 2026-06-16

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

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

08.
arXiv (CS.CV) 2026-06-16

Explainable Task-Oriented Token Communication for AI-Native 6G Networks

The integration of Foundation Models (FMs) and wireless communications is driving the evolution of image communication from bit-accurate transmission toward task-oriented transmission. However, existing task-oriented image communication methods still face three major challenges: insufficient task-oriented Token representation, inadequate collaboration between Visual Tokens and Task Tokens, and limited interpretability of task decisions. To address these challenges, we propose an Explainable Task-Oriented Token Communication (ET-TokenCom) framework. By treating Tokens as unified units for information representation and transmission, the proposed framework constructs an end-to-end communication link that spans visual perception, wireless transmission, and task reasoning. At the transmitter, the ET-TokenCom framework extracts Visual Tokens from images to preserve low-level visual information. Meanwhile, Task Tokens generated by the FM are introduced to represent the target information and decision intent required by the current task. A Cross-Modal Attention (CMA) fusion mechanism is further designed, enabling Task Tokens to explicitly guide the selection, weighting, and transmission of Visual Tokens. At the receiver, the framework integrates Token decoding with an explainable output mechanism, where attention heatmaps are generated to highlight critical perceptual regions under different task objectives and reveal the influence of Task Tokens on the outputs. Finally, simulation results validate the effectiveness and robustness of the proposed ET-TokenCom framework.

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

Better Adherence, Richer Context: A Field Evaluation of LLM-Powered Conversational Voice Diaries for Sleep

arXiv:2606.18596v1 Announce Type: cross Abstract: Sleep diaries are central to behavioral sleep medicine and cognitive behavioral therapy for insomnia, yet daily completion is difficult to sustain, and static forms often provide limited context for interpreting night-to-night sleep variation. We designed an LLM-powered conversational voice diary that delivers clinically grounded morning and evening sleep diary questions through proactive smart-speaker prompts, structured conversational intake, and adaptive follow-up dialogue. We evaluated the system in a four-week between-subjects field study with 30 university students, comparing it with a text-based mobile diary using matched diary items, reporting windows, and reminder intervals. Compared with the text-based diary, the conversational voice diary showed higher adherence and elicited more detailed contextual self-report about routines, stressors, environmental conditions, and other sleep-related factors. Participants also described the voice diary as easier to integrate into daily routines, despite longer perceived completion time. However, voice-based conversational intake produced lower completeness for some structured diary fields, revealing a trade-off between expressive richness and structured precision. These findings show both the promise and the challenge of using LLM-powered conversational voice assistants for longitudinal health self-report.

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

Variational Deep Unfolding with Mamba-Based Nonlocal Modeling for Underwater Image Enhancement

Underwater imaging plays a crucial role in ocean engineering, although captured data often suffer from poor visibility and color distortion. To address these challenges, we propose a model-based deep unfolding network for underwater image enhancement that integrates variational modeling into a learnable architecture. The framework is guided by a variational formulation based on a dehazing decomposition, incorporating a multiplicative residual component to absorb remaining artifacts and a nonlocal gradient-type constraint to preserve structural details and enhance edge sharpness. We provide a theoretical analysis establishing the existence of solution for the associated minimization problem. The proposed unfolding method incorporates Mamba layers to efficiently capture self-similarities in the scene. In addition, we introduce a proximal trajectory loss that enforces consistency between the unfolding stages and the iterations of an ideal restoration regularizer. Experimental results demonstrate that the proposed unfolding approach achieves improved visual quality and competitive quantitative performance compared with recent state-of-the-art methods. The source code will be available at https://github.com/MIA-UIB/Variational-Unfolding-Mamba-Underwater-Enhancement .

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

Adaptive Domain Models: Bayesian Evolution, Warm Rotation, and Principled Training for Geometric and Neuromorphic AI

arXiv:2603.18104v5 Announce Type: replace Abstract: Prevailing AI training assumes reverse-mode automatic differentiation over IEEE-754 arithmetic. The memory overhead of training relative to inference, optimizer complexity, and structural degradation of geometric properties through training are consequences of this arithmetic substrate. This paper develops an alternative training architecture grounded in three prior results: the Dimensional Type System and Deterministic Memory Management framework (Haynes 2026), which establishes stack-eligible gradient allocation and exact quire accumulation as design-time verifiable properties; the Program Hypergraph (Haynes 2026), which establishes grade preservation through geometric algebra computations as a type-level invariant; and the b-posit bounded-regime design (Jonnalagadda et al. 2025), which makes posit arithmetic tractable across hardware targets conventionally considered inference-only. Their composition enables depth-independent training memory bounded to approximately twice the inference footprint, grade-preserving weight updates, and exact gradient accumulation, applicable uniformly to loss-function-optimized and spike-timing-dependent neuromorphic models. We introduce *Bayesian distillation*, a mechanism by which the latent prior structure of a general-purpose model is extracted through the ADM training regime, resolving the data-scarcity bootstrapping problem for domain-specific training. For deployment, we introduce *warm rotation*, an operational pattern in which an updated model transitions into an active inference pathway without service interruption, with correctness formalized through PHG certificates and signed version records. The result is a class of domain-specific AI systems that are smaller and more precise than general-purpose models, continuously adaptive, verifiably correct with respect to the physical structure of their domains, and initializable from existing models.

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

Metadata-Aware Multi-Prompt Reasoning for Zero-Shot Accident Understanding

In this paper, we address the problem of zero-shot understanding of accidents from surveillance videos by identifying when an impact event occurs, what type of impact it is, and where in the frame it occurs using natural language. We propose a three-stage pipeline that decomposes the accident understanding into when, what, and where. The first stage extracts a short temporal window around the impact using vision-language similarity. In the second stage, we perform metadata-driven multi-prompt reasoning with five complementary views (baseline, motion, geometry, contrast, and tiebreaker) and resolve disagreement via an entropy-gated pairwise adjudicator. Finally, we localize the impact of an open-vocabulary detector queried on the predicted accident type and scene layout, and aggregate detections across keyframes using a score-weighted centroid. Our pipeline achieves a substantial improvement in the harmonic-mean score over a centre-of-frame baseline on the zero-shot ACCIDENT @ CVPR benchmark. We show that decomposing zero-shot video understanding into temporal localization, semantic classification, and spatial grounding enable more reliable reasoning with vision-language models than direct prompting alone.

14.
arXiv (CS.AI) 2026-06-25

What Does It Mean to Break a Distillation Defense?

arXiv:2606.25059v1 Announce Type: cross Abstract: Black-box LLMs (accessible only via API) are vulnerable to distillation attacks, in which an attacker queries the model and trains a student on its outputs. A recent line of work proposes output perturbation defenses that modify the teacher's output to reduce student performance while preserving utility for legitimate users. As a relatively new family of approaches, output perturbation defenses lack a shared threat model, making it difficult to compare them, reason about composing them with other attacks, or evaluate their robustness against realistic adversaries. This underspecification matters beyond technical evaluation: when defenses are deployed to protect intellectual property or justify regulatory compliance, an imprecise threat model can create a false sense of security. We propose a threat model framework that describes attackers along three dimensions: a query budget, a data budget, and an interface profile that captures how attackers interact with the API. Using antidistillation sampling as a case study, we show that whether the defense is considered effective depends on the assumed threat model. We argue that future work on distillation defenses, along with any governance or policy frameworks built around them, should explicitly specify and stress-test attacker capabilities along our three dimensions.

15.
arXiv (math.PR) 2026-06-15

Boltzmann-Like Occupation of Nonequilibrium Steady States on Dense Networks

arXiv:2606.14542v1 Announce Type: cross Abstract: A central problem in statistical physics is to extend the Boltzmann distribution to nonequilibrium steady states (NESS). We prove that NESS on large dense networks have Boltzmann-like occupation despite extensive entropy production. We further show that the active-matter heuristic of "low rattling" is asymptotically exact. Intuitively, these NESS spend a greater fraction of their time in states they leave more slowly. This explanation extends to the broader class of "equiaccessible" steady states, which play a role in our analysis akin to that of equilibrium in linear response.

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

PLAIground: SLO-Driven Runtime Model Selection for Compound AI Systems in the Edge-Cloud-Space Continuum

arXiv:2606.14356v1 Announce Type: cross Abstract: Applications in the 3D Computing Continuum, which unifies edge, cloud, and space, require combining multiple AI tasks such as object detection, time-series analytics, and natural language processing into Compound AI systems. These systems must satisfy stringent Service Level Objectives (SLOs) on accuracy, latency, and cost. A key mechanism for maintaining SLO compliance of Compound AI systems is runtime model selection, where AI models are dynamically switched for each workflow task. However, existing distributed and compound AI frameworks do not natively support runtime model selection. We present PLAIground, a framework that enables runtime model selection for Compound AI systems. PLAIground introduces Compoundable AI Model (CAIM) abstraction, which decouples task semantics from AI model implementations via Task and Data Contracts, enabling model switching without workflow changes. Additionally, PLAIground introduces Pixie, an SLO-driven runtime model selection algorithm, which dynamically selects the most suitable model for each task during execution. Our evaluation on two realistic Compound AI workflows demonstrates that Pixie achieves up to 91.3% accuracy while maintaining SLO compliance where fixed-model strategies either violate cost and latency budgets up to 21x or miss accuracy targets by 4%.

17.
arXiv (CS.AI) 2026-06-25

Attractive and Repulsive Pattern Control in Sequence Generation

arXiv:2606.24911v1 Announce Type: cross Abstract: Variable-order Markov models preserve local symbolic syntax by adapting context length, but long continuations can enter recurring high-order "tunnels": repeated suffixes, locally periodic passages, or copied fragments longer than the formal Markov order. This paper introduces signed pattern control for variable-order Markov generation with BP-Regular sampling. A weighted recurrence automaton computes an activation R for a chosen family of target patterns, and belief propagation samples exactly from P_beta(x) proportional to P_0(x) exp(beta R(x)). Negative coupling makes the target patterns costly during sampling; positive coupling rewards the same patterns and turns them into controlled attractors. The target family may be mined online from overactive generated material, supplied by a score or style vocabulary, or designed as an experimental probe. The main experiments use the online homeostatic case, choosing patterns that become overactive in the sampling history. On six duration-bearing monophonic sources, including Bach and Telemann material, the negative branch reduces generated 8-gram self-reuse, increases the effective number of generated 8-grams, and increases coverage of training-supported 4-gram contexts while preserving substantial lower-order support. A pitch-sequence replication on five Weimar Jazz Database solos gives the same anti-reuse signature outside Baroque material. The same signed mechanism also provides a positive branch for probing attractor basins, phase transitions, and hysteresis in the underlying variable-order model.

18.
arXiv (CS.AI) 2026-06-25

OncoSynth: Synthetic data generation for treatment effect estimation in oncology

arXiv:2606.25762v1 Announce Type: cross Abstract: In oncology, access to patient-level data is often restricted. Synthetic data provides an alternative for analyzing treatment effectiveness, but existing methods for synthetic data generation fail to preserve the causal relationships between covariates, treatments, and outcomes, thereby leading to biased estimates of treatment effects. Here, we introduce OncoSynth, a generative, causally-aware machine learning framework designed to produce synthetic cohorts that enable accurate estimation of population- and patient-level treatment effects. OncoSynth uses a diffusion-based sequential approach to model how covariates influence treatment assignment and how treatment affects survival. We evaluate OncoSynth using large lung (N = 37,128) and breast cancer (N = 17,046) cohorts. Our results show that OncoSynth generates high-fidelity synthetic patient cohorts that preserve real-world patient, treatment, and outcome distributions. Notably, OncoSynth improves treatment effect estimation over existing approaches, by reducing population-level treatment effect error by up to 66%, and patient-level treatment effect error by up to 58%. Thereby, OncoSynth supports reliable evidence generation for precision oncology in settings where data sharing is restricted.

19.
arXiv (CS.LG) 2026-06-24

Extended pseudo-spectral physics-informed neural networks for phase-field models

arXiv:2606.24660v1 Announce Type: cross Abstract: Phase-field models play a central role in the continuum description of phase separation, in which the bulk free-energy density and the interfacial thickness parameter determine pattern formation and microstructural evolution. In practice, these constitutive quantities are rarely known a priori and must be inferred from limited dynamical observations. In this work, an extended pseudo-spectral physics-informed neural network (ESPINN) framework is developed for the inverse identification of phase-field models from transient snapshot data. It enables the simultaneous recovery of both the bulk chemical potential and unknown gradient coefficients. Numerical experiments on the one-dimensional Cahn-Hilliard equation demonstrate accurate and statistically stable reconstruction in the noiseless regime, with substantial constitutive information recoverable from even a single snapshot pair. In the presence of noise, reconstruction accuracy degrades gracefully, and increasing the number of snapshots improves robustness by reducing variance across runs. These results establish ESPINN as a data-efficient and physically consistent approach for learning free-energy structure in continuum models of phase separation.

20.
arXiv (quant-ph) 2026-06-16

Ultrastrongly coupled open systems and fine grained time

arXiv:2606.16634v1 Announce Type: new Abstract: We study the dynamics of a d-level quantum system coupled to a bosonic reservoir when the coupling constant is large. It is known that in the limit of infinite coupling strength, the system undergoes an instantaneous nonselective measurement, resulting in the immediate decoherence in the measurement basis, followed by a unitary Zeno dynamics. Here we resolve this dynamical process by introducing a fine grained scaling regime of short times proportional to the inverse coupling. We provide a rigorous derivation of the open system dynamics in this regime of ultrastrong coupling and demonstrate how decoherence unfolds continuously in the new time scale. We show that Markovian dynamics which are not given by semigroups arise naturally, in contrast to what happens in the weak coupling theory.

21.
Nature (Science) 2026-06-10

Hybrid refinery process turns plant material into industrially important chemical

An ingredient of nylon has been made in high yields from lignin — revealing a fresh strategy for turning this complex plant biopolymer into industrial chemicals. An ingredient of nylon has been made in high yields from lignin — revealing a fresh strategy for turning this complex plant biopolymer into industrial chemicals.

22.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

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

RLCSD: Reinforcement Learning with Contrastive On-Policy Self-Distillation

On-policy self-distillation (OPSD) provides dense, token-level supervision for reasoning models by aligning a model's own distribution with the distribution it produces under privileged context, typically a verified solution. However, we show that the learning signal drawn from this distributional gap concentrates on style tokens rather than task-bearing ones, as the hinted model tends to produce more direct, shorter outputs. We term this pathology privilege-induced style drift, which destabilizes training or causes response length to shrink. To address this, we propose RLCSD (Reinforcement Learning with Contrastive on-policy Self-Distillation), which mitigates this drift by contrasting the teacher-student gap under a correct hint against that under a wrong hint, suppressing the style shift that conditioning on a hint tends to induce regardless of correctness, and yielding a signal that is more concentrated on task-bearing tokens. Experiments on Qwen3 (1.7B/4B/8B) and Olmo-3-7B-Think across mathematical and logical reasoning show that RLCSD consistently outperforms GRPO and prior OPSD methods. We further show that the contrastive principle is general: it plugs into existing OPSD methods to improve them, and its underlying insight extends to the broader cross-model on-policy distillation setting.

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

Probing, Fusion, and Trustworthiness: A Systematic Evaluation of Foundation Model Representations for Multimodal Cancer Analysis

arXiv:2606.17115v1 Announce Type: cross Abstract: Foundation models (FMs) have emerged as powerful representation extractors for medical data, yet their generalizability to datasets under distribution shift remains underexplored. This work systematically evaluates FM-based representations on a suite of computational pathology tasks across two real-world commercial cohorts, IH-BC and IH-NSCLC, drawn from the licensed in-house (IH) oncology dataset. The analysis focuses on two modalities, whole-slide images and transcriptomic profiles, drawn from the IH multimodal data. We first benchmark unimodal probing performance across five FMs on eight downstream classification tasks, and find that image and omics representations carry complementary predictive signals. Then we investigate whether multimodal fusion can yield additional gains over unimodal baselines by comparing three image-omics fusion strategies built on paired representations. The trustworthiness of selected unimodal and multimodal pipelines is further assessed through conformal prediction. Our results show that FM representations achieve competitive performance on out-of-distribution data and that multimodal fusion helps mainly when no single modality dominates the signal. Conformal prediction reveals that in the majority of cases where a point prediction fails, the true diagnosis remains recoverable within the prediction set, reinforcing the value of uncertainty-aware inference for clinical support.

25.
arXiv (CS.LG) 2026-06-18

Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning

arXiv:2604.14906v3 Announce Type: replace-cross Abstract: The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through $-$1 programmed ribosomal frameshifting ($-1$ PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of $-$1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the $-$1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.