Predictive modeling in biology and medicine: Digital twins and multi-scale modeling
by Mark Alber, Amber Smith, Reinhard Laubenbacher, Roeland M. H. Merks
Academic Intelligence · Curated Daily
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by Mark Alber, Amber Smith, Reinhard Laubenbacher, Roeland M. H. Merks
arXiv:2604.22167v2 Announce Type: replace-cross Abstract: Language models are increasingly capable and are being rapidly deployed on a population-level scale. As a result, the safety of these models is increasingly high-stakes. Fortunately, advances in alignment have significantly reduced the likelihood of harmful model outputs. However, when models are queried billions of times in a day, even rare worst-case behaviors will occur. Current safety evaluations focus on capturing the distribution of inputs that yield harmful outputs. These evaluations disregard the probabilistic nature of models and their tail output behavior. To measure this tail risk, we propose a method to efficiently estimate the probability of harmful outputs for any input query. Instead of naive brute-force sampling from the target model, where harmful outputs could be rare, we operationalize importance sampling by creating unsafe versions of the target model. These unsafe versions enable sample-efficient estimation by making harmful outputs more probable. On benchmarks measuring misuse and misalignment, these estimates match brute-force Monte Carlo estimates using 10-20x fewer samples. For example, we can estimate probability of harmful outputs on the order of 10^-4 with just 500 samples. Additionally, we find that these harmfulness estimates can reveal the sensitivity of models to perturbations in model input and predict deployment risks. Our work demonstrates that accurate rare-event estimation is both critical and feasible for safety evaluations. Code is available at https://github.com/rangell/LMTailRisk
Time-series anomaly detection (TSAD) is critical in domains such as industrial monitoring, healthcare, and cybersecurity, but it remains challenging due to rare and heterogeneous anomalies and the scarcity of labelled data. This scarcity makes unsupervised approaches predominant, yet existing methods often rely on reconstruction or forecasting, which struggle with complex data, or on embedding-based approaches that require domain-specific anomaly synthesis and fixed distance metrics. We propose ASTER, a framework that generates pseudo-anomalies directly in the latent space, avoiding handcrafted anomaly injections and the need for domain expertise. A latent-space decoder produces tailored pseudo-anomalies to train a Transformer-based anomaly classifier, while a pre-trained LLM enriches the temporal and contextual representations of this space. Experiments on three benchmark datasets show that ASTER achieves state-of-the-art performance and sets a new standard for LLM-based TSAD.
arXiv:2606.14897v1 Announce Type: cross Abstract: Air traffic growth, advanced air mobility, and increasingly autonomous operations are driving the need for scalable and adaptive airspace design methodologies. Central to this challenge is quantifying how traffic flow structure and demand, governed in part by airspace geometry, influence conflict generation and operational complexity. This paper presents an analytical framework for computing conflict rate and conflict probability in structured airspace using stochastic flow models. Traffic streams are modeled as renewal processes with prescribed inter-arrival time distributions, while interactions between flows are captured through geometry-dependent minimum spacing constraints at merges and crossings. Within this formulation, closed-form upper bounds on the expected conflict rate and conflict probability per aircraft are derived as functions of flow configuration and demand. These metrics are interpreted as complementary measures of airspace complexity, reflecting controller workload and per-aircraft operational risk. The methodology is applied to representative hexagonal cell geometries with varying routing structures and flow distributions. Results reveal non-monotonic tradeoffs between routing flexibility, capacity, and conflict generation, with intermediate flow configurations outperforming both highly constrained and highly distributed cases. The proposed framework provides a tractable tool for evaluating airspace design alternatives and complexity-informed traffic management strategies.
arXiv:2602.09303v2 Announce Type: replace Abstract: We propose a physics-informed consistency modeling framework for solving partial differential equations (PDEs) via fast, few-step generative inference. We identify a key stability challenge in physics-constrained consistency training, where PDE residuals can drive the model toward trivial or degenerate solutions, degrading the learned data distribution. To address this, we introduce a structure-preserving two-stage training strategy that decouples distribution learning from physics enforcement by freezing the coefficient decoder during physics-informed fine-tuning. We further propose a two-step residual objective that enforces physical consistency on refined, structurally valid generative trajectories rather than noisy single-step predictions. The resulting framework enables stable, high-fidelity inference for both unconditional generation and forward problems. We demonstrate that forward solutions can be obtained via a projection-based zero-shot inpainting procedure, achieving consistent accuracy of diffusion baselines with orders of magnitude reduction in computational cost.
Tokyo experienced a measles outbreak (260 cases) in early 2026 despite elimination status. Adults aged 20-39 years were most affected, and 38% of cases were modified measles, increasing with prior vaccination. Although incidence rose until April, the effective reproduction number; R(t) fell below 1, consistent with outbreak control. Multiple clusters were identified, but many cases lacked epidemiological links, suggesting that modified measles is less likely to be considered in differential diagnosis. Intensive contact tracing and surveillance contributed to limiting transmission.
Commercially available make-on-demand libraries now exceed 100 billion compounds, requiring over 50 years to screen on 2,000 CPU cores using conventional docking. We present two complementary approaches to address this challenge. CombiDOCK, a combinatorial docking framework, enables exhaustive screening at the 100-billion scale within 40 days. MINT-Dock, a generative framework, accelerates navigation of this space by integrating CombiDOCK with Monte Carlo Tree Search. Benchmarked on 46 diverse targets, CombiDOCK matched full-molecule docking accuracy, and MINT-Dock achieved a 4,800-fold enrichment over random selection. Compared with prior billion-scale brute-force campaigns against {sigma}2, VMAT2, and VAChT, prospective CombiDOCK screens of the 100-billion-molecule library yielded higher hit rates and more potent ligands, while MINT-Dock achieved comparable outcomes across single- and multi-target objectives with >20-fold computational cost reductions. Docking-predicted poses of the best VAChT-binding compounds were confirmed by cryo-EM structures. These methods provide exhaustive and generative paths for navigating the trillion-molecule frontier of drug discovery.
Automatic metrics are the default for evaluating LLM-generated text, yet a metric is quietly asked to do two jobs: tell genuine content alignment from surface coincidence (validity), and tell a better system from a worse one (discriminative power). On open-ended, opinion-driven question answering, the two are in tension. We introduce RECOM (Reddit Evaluation for Correspondence of Models), a contamination-free evaluation dataset of 15,000 r/AskReddit questions (September 2025), each paired with its authentic community replies, which postdate every evaluated model's training cutoff. Scoring five open-source LLMs (7–10B) against every reply each metric paired with a random-derangement noise floor we find that no metric does both jobs well. Cosine similarity separates real from random answers (Cohen's $d \approx 2$) but cannot rank the five models ($|d| < 0.1$); BERTScore precision appears to rank the models (raw $|d|$ up to 0.63), but once response length is controlled this collapses to $|d| = 0.09$ and its validity is weak ($d \approx 0.8$, versus cosine's $\approx 2$). Because every metric scores the same outputs, this validity–discrimination tradeoff is a property of the metrics, not the models, and we argue it stems from representation design. Three independent LLM judges reproduce the validity gap and likewise separate the five models only weakly. We recommend reporting metrics on both axes, with an explicit random-baseline floor. RECOM is publicly available at https://anonymous.4open.science/r/recom-D4B0
arXiv:2604.24806v2 Announce Type: replace-cross Abstract: Modern Deep Learning Recommendation Models (DLRMs) follow scaling laws with sequence length, driving the frontier toward ultra-long User Interaction History (UIH). However, the industry-standard "Fat Row" paradigm, which pre-materializes these sequences into every training example, creates a storage and I/O wall where data infrastructure usage exceeds GPU training capacity due to data redundancy that is amplified in multi-tenant environments where models with vastly different sequence length requirements share a union dataset. We present a versioned late materialization paradigm that eliminates this redundancy by storing UIH once in a normalized, immutable tier and reconstructing sequences just-in-time during training via lightweight versioned pointers. The system ensures Online-to-Offline (O2O) consistency through a bifurcated protocol that prevents future leakage across both streaming and batch training, while a read-optimized immutable storage layer provides multi-dimensional projection pushdown for heterogeneous model tenants. Disaggregated data preprocessing with pipelined I/O prefetching and data-affinity optimizations masks the latency of training-time sequence reconstruction, keeping training throughput compute-bound by GPUs. Deployed on production DLRMs, the system reduces training data infrastructure resource usage while enabling aggressive sequence length scaling that delivers significant model quality gains, serving as the foundational data infrastructure for modern recommendation model architectures, including HSTU and ULTRA-HSTU.
arXiv:2606.12058v1 Announce Type: cross Abstract: Attention is the key mechanism underlying in-context learning in transformers, and attention patterns have been observed empirically to emerge abruptly during training. We present a Bayesian theory of feature learning in attention; we then focus on how the copy subcircuit in the first layer of an induction head is learned by analyzing a single-layer softmax attention network trained on a copy task. We derive a closed-form posterior over the attention matrix and reduce it to a low-dimensional order parameter space. This reduction reveals a phase transition in the amount of training data, which we verify using both Bayesian sampling and standard training with Adam. We contrast our results with linear attention and find that softmax attention exhibits a first-order phase transition while in linear attention an initial second-order phase transition is followed by a smooth, continuous evolution toward the structured attention pattern (crossover). Our work provides a first-principles theoretical account of the abrupt emergence of the copy subcircuit, reminiscent of the one observed in training large language models.
arXiv:2606.17709v1 Announce Type: new Abstract: We find that the substantial advantages predicted for bias-tailored quantum error correction (QEC) under code-capacity noise are strongly reduced once realistic syndrome extraction and circuit-level noise models are considered. We start by comparing XZZX codes to rectangular surface codes with a bias-dependent optimised anisotropy. Although code-capacity simulations predict an advantage of rectangular surface codes in the limit of high noise bias, this actually disappears under circuit-level noise, making the XZZX codes the preferred and simplest choice even for platforms that allow for a flexible variation of the code layout adapted to changes in noise calibration. Our results identify bias degradation during syndrome extraction under circuit-level noise as the central limitation of biased-tailored QEC. To partially mitigate this effect, we introduce a bias-filtering CNOT gadget that temporarily encodes the ancillary target qubit during syndrome extraction in a repetition code and, upon measurement and feed forward, manages to reduce the bias degradation. In a regime of high-bias and low-idle errors, this bias-filtering gadget yields a few-percent relative improvement of the XZZX code error threshold, demonstrating that lightweight bias-filtering strategies can recover part of the lost bias-tailoring advantage for realistic circuit-level noise.
arXiv:2601.03035v2 Announce Type: replace Abstract: This is a set of lectures on tensor networks with a strong emphasis on the core algorithms involving Matrix Product States (MPS) and Matrix Product Operators (MPO). Compared to other presentations, particular care has been given to disentangle aspects of tensor networks from the quantum many-body problem: MPO/MPS algorithms are presented as a way to deal with linear algebra on extremely (exponentially) large matrices and vectors, regardless of any particular application. The lectures include well-known algorithms to find eigenvectors of MPOs (the celebrated DMRG), solve linear problems, and recent learning algorithms that allow one to map a known function into an MPS (the Tensor Cross Interpolation, or TCI, algorithm). The lectures end with a discussion of how to represent functions and perform calculus with tensor networks using the "quantics" representation. They include the detailed analytical construction of important MPOs such as those for differentiation, indefinite integration, convolution, and the quantum Fourier transform. Three concrete applications are discussed in detail: the simulation of a quantum computer (either exactly or with compression), the simulation of a quantum annealer, and techniques to solve partial differential equations (e.g. Poisson, diffusion, or Gross-Pitaevskii) within the "quantics" representation. The lectures have been designed to be accessible to a first-year PhD student and include detailed proofs of all statements.
arXiv:2606.10642v2 Announce Type: replace Abstract: Machine learning weather prediction (MLWP) models have achieved impressive forecasting performance at a small fraction of the computational costs required for traditional physics-based methods. However, they are primarily (1) data-driven and (2) evaluated using pixel-wide error metrics (e.g., RMSE), so there are no guarantees that their forecasts are consistent with known physical laws. We introduce PhysMetrics$.$Weather, an evaluation framework that assesses the physical realism of MLWP models across three types of metrics: conservation, spectral, and dynamical. By quantifying physical realism, this tool guides the development of physics-informed architectures and helps evaluate whether MLWP models are reliable for operational use. Our framework is available on Github at https://github.com/Emmakast/PhysMetrics.Weather.
High-quality 4D head avatars from one or a few source portraits are central to telepresence, AR/VR, and digital-human interaction. 3D Gaussian Splatting (3DGS) has emerged as the dominant representation, with two complementary regimes (generalizable feed-forward predictors and per-subject refiners) maturing in parallel. However, existing feed-forward predictors are trained on a single dataset family with a hard-coded source count, inheriting the corresponding domain bias. Per-subject refiners require 300K–600K iterations and rely on adaptive densification that destroys upstream Gaussian layouts, preventing the two regimes from sharing a representation end-to-end. To bridge both regimes we propose SpatialAvatar-0 on a shared FLAME-mesh-bound Gaussian representation: a feed-forward generator with a parameter-free K-source mean-pool and a monocular-temporal to multi-view-spatial two-phase schedule that anchors against identity-prior collapse onto the smaller multi-view set. We further introduce a 10K-iter layout-preserving per-subject refinement loop that freezes the FLAME-binding and Gaussian count and replaces densification with a three-component anti-spike regularization. On VFHQ/HDTF cross-domain zero-shot we surpass the in-domain leader GAGAvatar by +1.5 dB PSNR despite never training on either test domain, and on the SplattingAvatar monocular benchmark we lead every reported metric, surpassing the 300K-iter GeoAvatar by +1.3 dB PSNR at up to 60x shorter per-subject schedule than common SOTA baselines. Website: https://spatialwalk.github.io/SpatialAvatar-0.
arXiv:2606.13054v1 Announce Type: cross Abstract: Large language models (LLMs) exhibit exceptional general language processing capabilities, but their memory and compute costs hinder deployment. Ternarization has emerged as a promising compression technique, offering significant reductions in model size and inference complexity. However, existing methods struggle with heavy-tailed activation distributions and therefore keep activations in high precision, fundamentally limiting end-to-end inference acceleration. To overcome this limitation, we propose TWLA, a post-training quantization (PTQ) framework that achieves 1.58-bit weight compression and 4-bit activation quantization while maintaining high accuracy. TWLA comprises three components: (1) Euclidean-to-Manifold Asymmetric Ternary Quantizer (E2M-ATQ) minimizes layer-output error under weight ternarization via a two-stage optimization from Euclidean initialization to manifold relocation; (2) Kronecker Orthogonal Tri-Modal Shaping (KOTMS) applies a Kronecker-structured orthogonal rotation to reshape weights into ternary-friendly tri-modal distributions, while the shared rotation statistically suppresses activation outliers; and (3) Inter-Layer Aware Activation Mixed Precision (ILA-AMP) explicitly introduces adjacent-layer second-order interaction costs in bit allocation and jointly optimizes for the layer-wise disparity of activation quantization gains induced by the shared orthogonal transform, preventing cascades triggered by a few weak layers. Extensive experiments demonstrate that TWLA maintains high accuracy under W1.58A4, while delivering significant inference acceleration. The code is available at .
arXiv:2606.19643v1 Announce Type: cross Abstract: Motivated by the privacy, sensitivity and sharing limitations of health data, we present a comprehensive pipeline for inference of Bayesian mixture models within a federated learning setting, i.e. when data cannot be fully shared or pooled across compute nodes. We adopt a Consensus Monte Carlo (CMC) approach, in which an MCMC algorithm is run independently within each data silo to estimate local posterior distributions, which are then aggregated to approximate the posterior over the full data. The variational CMC approach of Rabinovich, Angelino and Jordan (2015) [1] frames the aggregation step as a variational inference problem, but their application to mixtures assumes the number of clusters and key mixture parameters to be known. Our main methodological contributions are: (i) an extension of variational CMC to over-fitted Bayesian mixture models that infer the number of clusters and all model parameters, without requiring conjugacy; (ii) novel cluster-matching algorithms suitable for cross-silo settings in which not every cluster appears in each local dataset; (iii) a number of inference strategies for the aggregation step, matched to different federated learning constraints; and (iv) guidelines for choosing among these in practice. A comprehensive simulation study validates the framework and allows us to compare to state-of-the-art federated learning alternatives. Notably, we show that when the composition of local datasets reflects the underlying clustering structure in the data, our approach can recover small clusters with greater accuracy than standard MCMC applied to the pooled data. We illustrate the framework on large-scale electronic health record data, identifying multi-morbidity patterns in a British geriatric population.
arXiv:2605.18250v3 Announce Type: replace-cross Abstract: Many dynamical systems can be described in terms of structured flows combining source/sink behavior, cyclic dynamics, and topology-constrained transport. These features arise across a wide range of physical, engineered, and data-driven systems. The objective of this work is to establish a unified perspective on such systems, to identify modeling approaches that balance expressivity, interpretability, computational complexity, and data requirements, and to investigate how highly expressive models can be used to uncover the dominant mechanisms underlying observed dynamics. Starting from the Helmholtz-Hodge decomposition of continuous vector fields, we review the recently proposed Graph Vector Field (GVF) framework and its discrete representation on simplicial complexes. We then introduce a hierarchy of alternative approaches, including parametric conditional models, linear graph dynamical systems, and reduced Hodge representations. Finally, we propose a verification and validation methodology based on benchmark datasets from well-understood physical systems and on systematic model-reduction and ablation studies. The resulting family of structured-flow models within a common framework, ranging from low-dimensional parametric representations to full GVF formulations, supports a diagnostic methodology in which gradient, curl, harmonic, and topological contributions are systematically assessed through ablation studies. This process enables the identification of dominant mechanisms underlying the observed dynamics and guides the construction of simplified models tailored to the available data and operational constraints. By separating structural verification, behavioral verification, and domain-specific validation, the proposed approach provides a foundation for scalable and interpretable analysis of complex dynamical systems across multiple application domains.
arXiv:2606.15190v1 Announce Type: new Abstract: In the era of early fault-tolerant quantum computing, basic demonstrations of entanglement operations between a few logical qubits are at the frontier of recent developments in quantum computing. In this work, we describe in detail, at both the logical and physical qubit levels, a logical teleportation protocol between two surface code logical qubits based on lattice surgery. We address several aspects of the teleportation protocol pertinent to superconducting qubit architectures. We explore the modularity constraints in the number and location of stabilizer readouts and compare variants of the teleportation protocol in this regard. Additionally, we investigate potential performance improvements related to in-sequence decision logic and the optimal size of the interface region between two surface code patches on a superconducting chip. Based on our simulations, we show possible near-term improvements in lattice surgery protocols that facilitate fault-tolerant quantum computing in superconducting circuit architectures.
arXiv:2605.29128v2 Announce Type: replace Abstract: The wide adoption of LLMs has led to their use in great variety of applications and scenarios, such as chatbot assistants and data annotation, creating the need for the models to satisfy certain budget and hardware constraints. This has led to the trend of LLMs being released in batches consisting of similar models of various sizes for the family of models to adhere to as wide of a range of constraints as possible. In this paper, we validate distillation and quantization as a cost-effective way to expand model families to new sizes and hardware formats. Based on the open-recipe Apertus 8B LLM, we produce Apertus-v1.1 - a distilled family of models with up to 4B parameters trained on 1.7T permissive license tokens. We demonstrate cost-efficiency and strong accuracy performance of our approach for covering large ranges of hardware and systems requirements.
arXiv:2606.16945v1 Announce Type: new Abstract: Large-momentum-transfer (LMT) atom interferometry provides a route toward enhanced inertial sensitivity in compact quantum sensors, but its scalability is limited by the accumulation of pulse-transfer errors across long Raman pulse sequences. We investigate theoretically the use of stimulated Raman shortcut-to-adiabatic passage (STIRSAP) for high-fidelity LMT atom optics in a Mach–Zehnder interferometer geometry. The counterdiabatic correction is encoded directly into the Raman pulse envelopes, eliminating the need for auxiliary microwave or radio-frequency control fields. Numerical simulations based on an effective Raman model show that $1~\mu\mathrm{s}$ STIRSAP pulses achieve single-pulse transfer fidelities of $F_\pi = 0.99902$ while maintaining negligible pulse-time overhead even at high momentum order. We analyze the resulting tradeoff between interferometric phase enhancement and compound contrast decay and identify an unconstrained shot-noise optimum near $n\approx270$. The analysis further shows that practical operation at extreme LMT order is constrained by wave-packet separation, vibration noise, Doppler detuning, and accumulated systematic effects rather than by pulse duration itself. These results establish superadiabatic Raman control as a promising approach for scalable high-fidelity atom optics and clarify the physical limitations governing compact high-order atom interferometers.
arXiv:2602.02466v2 Announce Type: replace Abstract: The paper solves the problem of continuum limit in bosonic thermal coherent-state path integrals. For this purpose, exact discrete versions of the path integral are constructed for three different orderings of the Hamiltonian: normal, anti-normal and symmetric (Weyl order). Subsequently, their different continuum versions are checked on the harmonic oscillator, to choose the symmetric ordering as a possibly correct choice for all polynomial Hamiltonians. Spotted mathematical subtleties in the simple case serve as a clue to the general solution. Finally, a general justification for the symmetric order is provided by deriving the continuum path integral starting from the exact discrete case using a renormalization procedure in the imaginary time frequency domain. While the role of Weyl order has already been found, the paper provides the missing proof of its suitability for every polynomial Hamiltonian and simplifies the previously established construction by referring only to creation and annihilation operators (without position and momentum operators).
arXiv:2606.20340v1 Announce Type: new Abstract: Because they have such long coherence times, nuclear spins have extraordinary potential for use in quantum information processing devices. However, coherent nuclear spin control generally requires external phase references, such as microwave control fields. Here, we phase-lock a $^{29}$Si nuclear spin ensemble in a silicon quantum dot using only the internal electronic spin-orbit coupling as a phase reference. When driven with the quantum-dot electrons, the nuclear spins align themselves to a phase determined by the electronic spin-orbit coupling and the timing of the drive protocol. This enables us to measure the coherent precession and inhomogeneous dephasing of the nuclear spins. We corroborate our results with detailed numerical simulations of the many-body electron nuclear system. Our work opens new routes for coherently controlling solid-state nuclear spin ensembles.
arXiv:2606.20467v1 Announce Type: new Abstract: Mathematicians understand a PDE solution through mathematical structures rather than tables of computed values. Historically, this has been the product of mathematical analysis, carried out by hand for each problem individually. Neither numerical simulation nor neural networks produce those structures directly. We propose Agentic Symbolic Search (ASYS), a prior-guided framework in which an agent translates PDE theory, public problem constraints, and accumulated search experience into testable differentiable symbolic programs. The mathematical forms are refined under evolutionary search, while their continuous parameters are fit by gradient-based optimization. This makes the search an automated form of inductive-bias injection rather than blind symbolic regression. For problems with known analytical forms, ASYS recovers these forms naturally; for other problems, ASYS constructs analytical approximations which can guide mathematicians toward further analysis. In our experiments, across five problems spanning bounded dynamics, finite-time blow-up, and free-boundary focusing, ASYS produces interpretable representations, including a geometric interface formula for Allen-Cahn 2D dynamics and a nine-parameter contraction law for Keller-Segel chemotactic blow-up, in settings where no closed-form description was previously available. ASYS shows the possibility of a new paradigm for characterizing PDE solutions, beyond handcrafted analytical solutions, mesh-based numerical solutions, and neural network approximations.
arXiv:2603.10827v2 Announce Type: replace-cross Abstract: Speech-aware large language models (LLMs) can accept speech inputs, yet their training objectives largely emphasize linguistic content or specific fields such as emotions or the speaker's gender, leaving it unclear whether they encode speaker identity. First, we propose a model-agnostic scoring protocol that produces continuous verification scores for both API-only and open-weight models, using confidence scores or log-likelihood ratios from the Yes/No token probabilities. Using this protocol, we benchmark recent speech-aware LLMs and observe weak speaker discrimination (EERs above 20% on VoxCeleb1). Second, we introduce a lightweight augmentation that equips an LLM with ASV capability by injecting frozen ECAPA-TDNN speaker embeddings through a learned projection and training only LoRA adapters. On TinyLLaMA-1.1B, the resulting ECAPA-LLM achieves 1.03% EER on VoxCeleb1-E, approaching a dedicated speaker verification system while preserving a natural-language interface.
Can financial news reliably predict short-term stock movements? Despite advances in large language models, this question remains unresolved. We revisit this problem using a zero-shot natural language processing framework, investigating whether models can extract actionable signals from financial news without domain-specific training. We design a structured pipeline that combines zero-shot natural language inference with temporal aggregation, explicitly modelling recency and event-dependent impact horizons when integrating information across articles. To address the need for transparency in high-stakes settings, we introduce a multi-layered explainability framework that links predictions to token-level, article-level, and aggregate evidence, and produces grounded natural language rationales. Across multiple models and prediction horizons, we find that zero-shot approaches consistently fail to outperform simple baselines, with particularly weak performance on negative movements, suggesting deeper structural limitations in mapping news sentiment to short-term price dynamics. However, explainability signals reliably distinguish between trustworthy and unreliable predictions, offering practical value even when accuracy is limited. These findings highlight the limits of zero-shot financial NLP and motivate a shift toward decision-support systems that prioritise transparency and uncertainty awareness. Code: https://github.com/alimert05/zero-shot-stock-xai