Academic Intelligence · Curated Daily

Explore the Frontier of Global Academia

AcademicHub aggregates real-time literature from top journals and preprint platforms. Build your personal research radar and let large language models compile cross-disciplinary analysis briefings automatically.

01.
arXiv (CS.CV) 2026-06-12

VISTA: Video Interaction Spatio-Temporal Analysis Benchmark

Existing benchmarks for Vision-Language Models (VLMs) primarily evaluate spatio-temporal understanding on simple single-action videos, closed attribute sets and restricted entity types, failing to capture the freeform, multi-action interactions between diverse entities which characterize real-world video understanding. Furthermore, the lack of a systematic framework for analyzing model failures across complementary spatio-temporal axes hinders comprehensive evaluation. To address these gaps, we introduce VISTA, a Video Interaction Spatio-Temporal Analysis benchmark designed for open-set, multi-entity and multi-action spatio-temporal understanding in VLMs. VISTA decomposes videos into interpretable entities, their associated actions, and relational dynamics, enabling multi-axis diagnostics and unified assessment of relational, spatial, and temporal understanding. Our benchmark integrates multiple datasets into a single interaction-aware taxonomy and comprises ~12K curated video-query pairs spanning diverse scenes and complexities. We systematically evaluate 11 state-of-the-art VLMs on VISTA, and break down aggregate performance across our taxonomy to reveal shortcomings and pronounced spatio-temporal biases obscured by traditional metrics. By providing detailed, taxonomy-driven diagnostics on a challenging dataset, VISTA offers a nuanced framework to guide advances in model design, pretraining strategies, and evaluation protocols. Overall, VISTA is the first, large-scale, interaction-aware diagnostic benchmark for spatio-temporal understanding in VLMs.

02.
bioRxiv (Bioinfo) 2026-06-15

SMLMFlow: Improving Structural Resolution in Single Molecule Localization Microscopy with Flow Matching

While Single Molecule Localization Microscopy (SMLM) aims to generate precise coordinates of molecular targets in cells, the resulting point clouds are inherently blurred by additive noise sources across the experimental, imaging, and processing workflow. This blurring often limits SMLM's ability to accurately quantify complex assembled structures required to address biological issues, despite reported localization precision down to a couple of nanometers. Here, we present SMLMFlow, a machine learning framework for improving structural resolution in SMLM datasets that combines a graph neural network and a hierarchical transformer with flow matching. We show that SMLMFlow improves structural resolution and downstream quantification across different structures, including filaments and protein nano-clusters, and generalizes to new unseen photophysics models.

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

Story Operators: Decomposing the Original $\to$ Sequel Transformation in Embedding Space

I treat a book as a point in a sentence-embedding space and a literary transformation as an operation on points. Given an original novel and its sequel, I ask what it takes, geometrically, to turn the first into the second. Using all-mpnet-base-v2 paragraph embeddings drawn from a precomputed index of the PG19 corpus, I form the displacement $d=\bar{x}_seq-\bar{x}_orig$ and greedily decompose it along a content basis obtained by PCA over the two books' own paragraphs. Each component is an interpretable axis anchored by real passages at its poles. Across thirteen verified author pairs from Project Gutenberg, the decomposition reveals a small taxonomy of sequels: formulaic (a tiny, low-rank change: Doyle's Holmes collections, $\|d\|=0.12$), concentrated (one dominant axis: Alcott's Little Women $\to$ Little Men, 75% on a single move), and compositional (many small axes: Twain, Burroughs's Barsoom, Nesbit). For the canonical case, Tom Sawyer $\to$ Huckleberry Finn, the dominant recovered axis is structural – the collapse of sheltering domesticity into a picaresque road – rather than the famous surface themes of vernacular voice or slavery, which ride later, smaller axes; and the transformation routes through adventure-journey space rather than diluting toward generic realism. I corroborate the recovered geometry against Twain's documented authorial intent (his 1875–76 letters to Howells), which names the first-person picaresque move years in advance, and I quantify, with an explicit representation caveat, how much of the realized transformation his stated intentions span. All computations are reproducible from the released scripts and data.

04.
medRxiv (Medicine) 2026-06-15

Validating Field-Feasible Measures of Recent Khat Use: A Diagnostic Accuracy Study Comparing Amphetamine Immunoassay and Assisted Self-Report Against HPLC in an Ethiopian Male Cohort

Background: Khat (Catha edulis) is a widely consumed natural amphetamine-analog used across East Africa and the Arabian Peninsula. Accurate field-feasible measurement of recent khat use is a prerequisite for large-scale epidemiological research; yet no validated alternatives to laboratory reference methods have been identified in the scientific literature. This nested validation study evaluated the diagnostic accuracy of two point-of-care measures, a commercial amphetamine immunoassay and a Timeline Followback (TLFB) Assisted Self-Report (ASR), against high-performance liquid chromatography (HPLC) quantification of urinary norephedrine (NE), while additionally assessing agreement between the two field measures. Methods: A prospective, random sub-sample of 119 male participants aged 18-40 years from the Gilgel Gibe Field Research Center (GGFRC) longitudinal cohort, Ethiopia (validation timepoint T2, 2015), was used. Three index-reference comparisons were conducted: (1) amphetamine immunoassay (nal von minden, Drug-Screen AMP test, 300 ng/mL cutoff) vs. HPLC; (2) binary ASR (past-week use) vs. HPLC; and (3) binary ASR vs. immunoassay. Sensitivity (positive percent agreement, PPA), specificity (negative percent agreement, NPA), positive predictive value (PPV), negative predictive value (NPV), overall accuracy (overall percent agreement, OPA), and Cohen's kappa were calculated with 95% confidence intervals. Pre-specified secondary analyses applied three pharmacokinetically-informed recall windows (0-2, 3-5, and 6-7 days prior to interview) to ASR. Results: Against HPLC (77 positive, 42 negative), the immunoassay showed perfect specificity (1.0 [0.916-1.0]) and PPV (1.0 [0.91-1.0]) but low sensitivity (0.52 [0.40-0.64]), NPV (0.53 [0.42-0.65]), overall accuracy (0.69 [0.60-0.77]), and weak kappa (0.43 [0.34-0.52]). Binary ASR showed high sensitivity (0.96 [0.89-0.99]), specificity of 0.60 [0.433-0.74], PPV (0.81 [0.72-0.89]), NPV (0.89 [0.72-0.98]), with overall accuracy 0.83 [0.75-0.89] and moderate kappa (0.60 [0.51,0.69]). Restricting ASR to use within 0-2 days improved specificity to 0.69 [0.52-0.84], PPV to 0.86 [0.77-0.93], overall accuracy to 0.87 [0.79-0.93], and kappa to 0.69 [0.61-0.78] (moderate), while sensitivity (0.96 [0.89-0.99]) and NPV (0.89 [0.72-0.98]) remained stable. Against the immunoassay, ASR achieved high PPA of (1.0 [0.91-1.0]), NPA of 0.35 [0.25-0.47], OPA of 0.57 [0.48-0.66], and minimal kappa (0.27 [0.19-0.35]). Conclusions: Time-stratified ASR (0-2 days) is a valid, scalable alternative to biological testing for recent khat use in resource-limited settings. The immunoassay's 300 ng/mL cutoff functions as a marker of heavy or recent high-dose khat use rather than any-use detection. Its perfect specificity and PPV make it valuable as a confirmatory test for substantial exposure, while its lower sensitivity reflects calibration to amphetamine rather than to khat-derived cathinone metabolite. Keywords: khat; Catha edulis; diagnostic accuracy; STARD; self-report; immunoassay; HPLC; Ethiopia; substance use measurement

05.
arXiv (CS.LG) 2026-06-18

Learning Augmented Exact Exponential Algorithms

arXiv:2606.18807v1 Announce Type: cross Abstract: The field of learning-augmented algorithms has demonstrated that machine-learned predictions can bypass worst-case lower bounds across a wide range of problems. So far, however, the focus has been almost exclusively on polynomial-time algorithms, where predictions improve competitive ratios, approximation guarantees, or running times. In this paper, we raise the question of whether predictions can push the frontier of exact exponential-time algorithms for NP-hard problems. We answer this question affirmatively by proposing a general approach that augments an entire family of state-of-the-art exact algorithms for a variety of subset selection problems. We show that a noisy predictor that is only marginally better than random guessing suffices to provably reduce the search space, and that the resulting runtime speedup scales smoothly with the prediction quality. Importantly, our algorithms require only pairwise independence of predictions or, alternatively, do not require the knowledge of the predictor's accuracy - both strictly weaker and more realistic settings than typically assumed.

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

Bridging data-driven priors via the score function for posterior sampling – Comparative review and experimental study

arXiv:2606.14800v1 Announce Type: cross Abstract: This paper reviews how a diverse set of popular data-driven priors commonly used in Bayesian inverse problems can be unified through their respective score functions. By framing these priors under this common perspective, we show that they can benefit from their straightfoward and effective integration into a recently proposed sampling algorithm. The applicability of this common framework is illustrated by considering several data-driven priors, namely regularization-by-denoising, normalizing flow-based priors, score-based generative models, and convex-ridge regularizers. For these four particular priors, the performance of the method is evaluated when conducting image inpainting and single image super-resolution. These results, as well as those obtained when restoring real images acquired in a geological context, demonstrate the efficiency of the method. This unified framework proves versatile enough to handle any posterior distribution defined by a broad class of score function-based priors, beyond the specific cases considered in this paper.

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

Variational Test-time Optimization for Diffusion Synchronization

Collaborative generation, which coordinates multiple diffusion trajectories to extend the capabilities of pretrained priors, has emerged as a powerful paradigm for extending the applicability of diffusion models. Among existing approaches, diffusion synchronization provides a scenario-agnostic solution by introducing general guidance mechanisms. However, current synchronization approaches rely heavily on heuristics and still require task-specific tailoring, which limits their generalizability and performance. In this work, we mathematically derive a synchronization framework based on optimal control, providing a principled explanation of diffusion synchronization. During sampling, we optimize control variables to guide multiple trajectories toward coherent solutions while remaining close to the underlying diffusion prior. Our method operates entirely at test-time without additional training, thereby enabling broad applicability across diverse generation scenarios when combined with strong pretrained priors. We demonstrate consistent improvements over baselines on three representative collaborative generation tasks, covering a wide range of modalities and applications. Beyond performance gains, our work establishes a novel foundation for collaborative generation, opening a principled path toward extending pretrained generative models to new collaborative generation settings.

08.
arXiv (CS.LG) 2026-06-15

High-Frequency Pricing at Scale for E-Commerce

arXiv:2606.13741v1 Announce Type: new Abstract: This paper presents the design, development, and implementation of a specialized forecast-then-optimize algorithmic pricing tool for sales campaigns in fashion e-commerce. Sales events present unique challenges for pricing including volatile demand patterns, rapid pricing decisions, and the need to balance short-term revenue with long-term profitability. We describe our approach combining daily-resolution demand forecasting using gradient-boosted trees with a multi-objective optimization framework that maximizes both long-term profit and net merchandise value for more than 5 million articles. Our solution addresses key limitations of existing weekly-granularity systems by implementing a forecast-then-optimize architecture that reduces pricing decision time from hours to minutes. We validate our approach through 23 A/B tests across 12 markets during 2023-2024 sales campaigns at Zalando, one of Europe's leading online fashion retailers. Experimental results demonstrate that the new pricing system achieves approximately 6% higher profit while maintaining equivalent performance on sales and revenue compared to the previous manual-algorithmic hybrid approach. Based on these results, the algorithm was successfully deployed to production and now handles the majority of algorithmic pricing decisions for sales campaigns at the company.

09.
arXiv (CS.AI) 2026-06-19

AI4SE and SE4AI Exploration: A Decade Looking Back and Forward

arXiv:2606.19630v1 Announce Type: new Abstract: The March 2020 INCOSE INSIGHT special issue on AI and Systems Engineering (SE) became the most downloaded issue in the publication's history and launched a research community that now draws over 250 registrants to its annual workshop. In this article, we trace the progress in AI and SE across three phases (labeled here foundational, applied, and LLM inflection) based on the authors' reading of the field's core papers, and describe our opinions of where the community has converged and where critical gaps remain. Separately, a human-AI agreement literature review leveraging both human expertise and six AI models was performed to assess the relevance of 1,712 INCOSE INSIGHT articles and 889 SERC publications. The results identify five critical research gaps and offer guidance for practitioners navigating AI adoption, assurance, and workforce transformation in SE. We share the agreement data and the AI4SE/SE4AI Explorer web application so readers can compare their own relevance judgments with the human and AI raters.

10.
arXiv (CS.LG) 2026-06-11

APEX: A Network-Native Time-Series Foundation Model for Forecasting and Anomaly Detection for Wireless Edge Operations

arXiv:2606.11553v1 Announce Type: new Abstract: Generic time-series foundation models transfer poorly to wireless network telemetry whose signals are bursty, zero-inflated, and coupled across protocol layers. We present APEX, a network-native, decoder-only transformer for forecasting enterprise AP telemetry, and evaluate it on DHCP degradation as a representative network task. APEX is pre-trained on 10-channel multivariate telemetry from ~4,500 production wireless networks (~100K AP time series, 34 metrics per AP), and is available as APEX-Large (269M, cloud) and APEX-Edge (10.5M, edge). On a 192-step (4-day) DHCP degradation benchmark, APEX-Large reduces MAE by 18% over the strongest foundation-model baseline (Toto) and 38% over SARIMA, with anomaly-detection F1 = 0.93, while APEX-Edge enables sub-second, privacy-preserving inference on AP-class edge hardware. These results suggest network-native pre-training is a practical foundation for proactive wireless operations.

11.
arXiv (CS.CL) 2026-06-24

Preferences of a Voice-First Nation: Large-Scale Pairwise Evaluation and Preference Analysis for TTS in Indian Languages

Crowdsourced pairwise evaluation has emerged as a scalable approach for assessing foundation models. However, applying it to Text to Speech(TTS) introduces high variance due to linguistic diversity and multidimensional nature of speech perception. We present a controlled multidimensional pairwise evaluation framework for multilingual TTS that combines linguistic control with perceptually grounded annotation. Using 5K+ native and code-mixed sentences across 10 Indic languages, we evaluate 7 state-of-the-art TTS systems and collect over 120K pairwise comparisons from over 1900 native raters. In addition to overall preference, raters provide judgments across 6 perceptual dimensions: intelligibility, expressiveness, voice quality, liveliness, noise, and hallucinations. Using Bradley-Terry modeling, we construct a multilingual leaderboard, interpret human preference using SHAP analysis and analyze leaderboard reliability alongside model strengths and trade-offs across perceptual dimensions.

12.
arXiv (CS.CV) 2026-06-24

Multilevel Stochastic Plug-and-Play for Sparse-View CT Reconstruction

Sparse-view computed tomography (SVCT) reduces radiation exposure and acquisition time, but the limited number of projection views makes the reconstruction problem severely ill-posed and leads to streak artifacts when analytical methods are used. Plug-and-Play (PnP) methods provide an effective way to combine data fidelity with learned image priors, while stochastic PnP methods further improve robustness by matching the denoiser input distribution through re-noising. However, these methods often require many iterations to converge, which limits their practical efficiency. In this work, we propose a multilevel (ML) stochastic PnP method for SVCT that accelerates stochastic PnP reconstruction. We highlight that, in the stochastic setting, directly enforcing prior coherence across levels would require accurately estimating fine-level prior gradients through multiple denoiser function evaluations, which substantially increases the computational cost. Motivated by this observation, we perform the multilevel steps in multiresolution analysis (MRA) approximation spaces. This choice is supported by the structure of the wavelet decomposition, which causes the prior-coherence correction to vanish in expectation, thereby avoiding costly estimation of fine-level stochastic prior gradients for the coarse-level corrections. Experiments on SVCT reconstruction show that our method, called Multilevel Stochastic Plug-and-Play (ML-SPnP), achieves reconstruction quality comparable to state-of-the-art methods while substantially reducing runtime.

13.
medRxiv (Medicine) 2026-06-23

Intrapartum Oxytocin and Maternal Outcomes Following Vaginal and Unscheduled Cesarean Delivery

Objective To examine whether intrapartum synthetic oxytocin exposure for labor induction or augmentation is associated with breastfeeding and postpartum depressive and traumatic stress symptoms. Methods We studied 1,296 postpartum women who delivered at a single tertiary care center, with assessments from the third trimester through approximately two months postpartum. Intrapartum oxytocin exposure was obtained from electronic medical records. Outcomes included exclusive breastfeeding, postpartum depression, and childbirth-related traumatic stress. Analyses were stratified by delivery mode and adjusted for key maternal and obstetric covariates. Results Overall, 63.3% of participants received intrapartum oxytocin. Among participants with vaginal delivery, oxytocin exposure was associated with lower exclusive breastfeeding at two months after adjustment (58.2% vs 70.3%; adjusted RR 0.86, 95% CI 0.76- 0.97; p = 0.02), but not with postpartum mental health outcomes. Among participants with unscheduled cesarean delivery, oxytocin exposure was independently associated with higher immediate postpartum depressive symptoms (F = 4.97, p = 0.03), acute childbirth-related stress (F = 4.56, p = 0.03), and two-month childbirth-related posttraumatic stress symptoms (F = 4.30, p = 0.04), but not two-month depressive symptoms. Conclusion Intrapartum oxytocin exposure was associated with lower exclusive breastfeeding after vaginal delivery and modestly higher childbirth-related distress after unscheduled cesarean delivery. These findings suggest that oxytocin exposure may mark or contribute to postpartum vulnerability in specific delivery contexts.

14.
arXiv (CS.CV) 2026-06-18

Quantile Transfer for Reliable Operating Point Selection in Visual Place Recognition

Visual Place Recognition (VPR) is a key component for localisation in Global Navigation Satellite System (GNSS)-denied environments, but its performance critically depends on selecting an image matching threshold (operating point) that balances precision and recall. Thresholds are typically hand-tuned offline for a specific environment and fixed during deployment, leading to degraded performance under environmental change. We propose a method that automatically selects the operating point of a VPR system to maximise recall at 100% precision. The method uses a small calibration traversal with known correspondences and transfers thresholds to deployment via quantile normalisation of similarity score distributions. This quantile transfer ensures that thresholds remain stable across calibration sizes and query subsets. Experiments with seven state-of-the-art VPR techniques across five benchmark datasets demonstrate that our proposed approach consistently outperforms existing baselines, enabling the underlying VPR technique to operate at 100% precision in approximately twice as many deployment scenarios (median improvement), while retrieving up to 29% more correct matches at that precision. The method eliminates manual tuning by adapting to new environments and generalising across operating conditions. Our code is available at https://github.com/DhyeyR-007/Quantile-Transfer-for-Reliable-VPR.

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

Speaking the Language of Science: Toward a General-Purpose Generative Foundation Model for the Natural Sciences

In this report, we present LOGOS (Language Of Generative Objects in Science), a scientific generative language model that unifies heterogeneous tasks across the natural sciences within a single autoregressive framework based on a shared scientific grammar. It encodes diverse scientific objects and their spatial interactions as token sequences over a common vocabulary. By representing spatial contact and constraint patterns as discrete tokens, the model captures complex structural interactions in a purely sequential manner, without relying on explicit coordinates or geometric neural networks. This unified representation enables a wide range of downstream tasks to be formulated consistently as next-token prediction in the same grammar space, creating strong alignment between continued multi-domain pre-training and downstream objectives. Across diverse tasks, LOGOS consistently matches or outperforms domain-specific baselines, providing preliminary evidence for the feasibility of "one model fits all" in the natural sciences. We train LOGOS models at different scales (1B, 3B, and 8B parameters) and find a consistent positive correlation between model size and performance. This suggests that the future of AI for Science (AI4S) may not lie in building an independent technical stack that is separated from large language models (LLMs). Instead, it may depend on deeply aligning scientific foundation models with LLMs through shared architectures, shared training paradigms, and shared inference infrastructure, so that LLMs can truly become a new entry point for AI4S. We release the model weights and associated resources to facilitate further research.

16.
arXiv (CS.AI) 2026-06-17

Functional Equivalence in Attention: A Comprehensive Study with Applications to Linear Mode Connectivity

arXiv:2606.17830v1 Announce Type: cross Abstract: Neural network parameter spaces are inherently non-injective, as distinct parameter configurations can realize identical functions through functional equivalence. While this symmetry is well understood in classical fully connected and convolutional models, it becomes substantially more intricate in modern attention-based architectures. Existing analyses of multihead attention have largely focused on the vanilla formulation, overlooking positional encodings that fundamentally reshape architectural symmetries. In this work, we provide a formal study of functional equivalence in Transformers with positional encodings. Focusing on the two most widely used variants–sinusoidal and rotary positional encodings (RoPE)–we show that sinusoidal encodings preserve the equivalence structure of vanilla attention, whereas rotary encodings significantly reduce the symmetry group, thereby enhancing expressivity. This offers a principled explanation for the growing prominence of RoPE in practice. We further examine how positional encodings affect linear mode connectivity, and through an alignment algorithm, empirically demonstrate that the presence and variability of connectivity across Transformer settings crucially depend on the positional encoding.

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

sebis at CRF Filling 2026: A Two-Stage Local LLM Pipeline for Medical CRF Filling

The extraction of structured clinical information from unstructured EHR notes is a persistent bottleneck in healthcare informatics. While large language models (LLMs) offer high performance, their deployment in clinical settings is hindered by privacy risks, inference costs, and the tendency to hallucinate beyond textual evidence. We address these challenges for the CL4Health 2026 Case Report Form (CRF) filling task by proposing a fully local, domain-adapted pipeline using the MedGemma-27B model. Our two-stage architecture, which separates binary presence classification from value extraction, enforces strict adherence to textual evidence and ensures deterministic outputs for negated, uncertain, or unknown states. By leveraging item-specific, few-shot in-context learning without external API calls or fine-tuning, our approach achieves a macro-F1 score of 0.55 on the official English test track. This result secures second place among all locally-hosted, open-source submissions. Our work demonstrates that privacy-preserving, on-premise LLM pipelines can achieve near-competitive performance with proprietary frontier models, providing a practical, data-sovereign framework for clinical NLP.

18.
arXiv (quant-ph) 2026-06-15

Physics-Informed Variational Quantum Classifier for Phase Detection in Strongly Correlated Matter

arXiv:2606.14489v1 Announce Type: new Abstract: The characterisation of quantum phases in strongly correlated systems is a crucial milestone for the deployment of quantum sensors. In this work, we present a Physics-Informed Variational Quantum Classifier (VQC) designed to detect the topological phase transition between the Fermi polaron quasiparticle and the molecular bound state. Unlike conventional Machine Learning approaches, our quantum architecture is constructed via the Trotterised time-evolution of an effective Hamiltonian, ensuring that the learnable parameters correspond to interpretable physical quantities. We show that the VQC efficiently discovers the optimal interferometric protocol, specifically the evolution time and effective bath interactions required to maximise the visibility of Ramsey fringes, thereby clearly distinguishing the Bose-Einstein Condensate (BEC) and Bardeen-Cooper-Schrieffer (BCS) regimes. Furthermore, we report the validation of this classifier on the QRed superconducting quantum processor (BSC-CNS). Despite the intrinsic hardware noise and decoherence, the VQC preserves the relative ordering of the topological phases. We demonstrate that the physics-informed architecture achieves a linear gate complexity $\mathcal{O}(N)$, bypassing the exponential memory wall of classical simulation and ensuring scalability to many-body regimes.

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

Counterfactual Explanations for Deep Two-Sample Testing

arXiv:2606.04009v2 Announce Type: replace-cross Abstract: Two-sample testing is a fundamental tool for detecting distributional differences across scientific domains, but classical tests (including kernel-based tests) can be ineffective on high-dimensional structured data such as images. Recent deep two-sample tests improve sensitivity in these settings by learning informative representations, yet they provide limited insight into which data features drive rejection of the null hypothesis $H_0$. To address this issue, we propose a counterfactual explanation framework for deep two-sample testing that generates sample-level edits moving observations from a source group toward a target group while explicitly reducing the discrepancy measured by the test. Our method combines a diffusion autoencoder with a pretrained deep two-sample test model and optimizes a maximum mean discrepancy (MMD) objective in the test model's representation space to produce plausible counterfactuals. We quantify distribution-level effects through changes in the test statistic and the resulting two-sample p-values. We evaluate the method on synthetic 2D shape datasets and two MRI cohorts. Across both settings, the counterfactual transformations consistently increase p-values relative to the original samples, indicating that the edited source set becomes statistically closer to the target distribution under the test. We measure minimality using LPIPS to ensure the counterfactuals remain close to the original samples. The resulting edits provide interpretable evidence of the features associated with the detected group differences. On MRI, the localized changes are consistent with known anatomical differences between cohorts.

20.
medRxiv (Medicine) 2026-06-24

External Validation and Calibration Assessment of Explainable Machine Learning Models for GVHD Prediction After Allogeneic HSCT

Background Graft versus host disease (GVHD) remains a major determinant of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo HSCT). Existing GVHD prediction models demonstrate modest discrimination and limited generalizability, and calibration drift across external populations is rarely characterized despite its essential role in the clinical interpretability of predicted probabilities. Objectives To develop and externally validate an explainable machine learning framework for predicting acute and chronic GVHD and associated overall survival in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS) undergoing allo HSCT, and to systematically characterize calibration across heterogeneous external validation cohorts to inform deployment requirements. Study Design The model was developed on three publicly available registry-derived datasets (N = 2,509) and externally validated across six independent cohorts (N = 14,788) comprising adult and pediatric allo HSCT recipients, including a regional Middle Eastern cohort (UAE and Jordan). A standardized preprocessing pipeline harmonized heterogeneous datasets. Gradient boosting models (CatBoost) were used for binary GVHD prediction; exploratory overall survival analysis used a Cox proportional hazards model with predicted acute GVHD risk as a covariate. Discrimination (AUROC with bootstrap 95% CI), calibration (logistic recalibration intercept and slope with analytical 95% CI), and feature importance (SHapley Additive exPlanations, SHAP) were assessed in training out-of-fold and all external cohorts. Results In internal validation, AUROC was 0.63 (95% CI 0.61-0.65) for acute GVHD and 0.72 (95% CI 0.70-0.74) for chronic GVHD. External validation demonstrated AUROC ranges of 0.51-0.57 (acute) and 0.54-0.64 (chronic), with consistent performance across disease subgroups despite substantial heterogeneity in transplant practices and feature availability. In exploratory survival analysis, the acute-GVHD-informed Cox model achieved a training-cohort C-index of 0.679 (95% CI 0.658-0.697); external C-indices ranged from 0.47-0.53. Calibration analysis identified systematic external risk overestimation (negative calibration intercept in 10 of 11 evaluable external cohort-target combinations) with heterogeneous slope drift requiring cohort-specific recalibration. Key predictors included recipient age, graft source, conditioning intensity, GVHD prophylaxis, and HLA match ratio. Conclusions An explainable, externally validated GVHD prediction framework was developed using heterogeneous registry-derived datasets, with systematic characterization of calibration drift across multiple external cohorts, an analysis rarely reported in prior GVHD prediction literature. Predictive performance was modest for acute GVHD and moderate for chronic GVHD, constrained by missing immunobiological variables and incomplete HLA characterization. Per-cohort recalibration is required before clinical deployment, with prospective validation and benchmarking against established GVHD risk scores identified as priority next steps.

21.
Nature (Science) 2026-06-17

Emergent decadal predictability in Antarctic contribution to sea-level rise

Despite large uncertainties associated with future mass loss from the Antarctic Ice Sheet, ice-sheet models show that the rate of sea-level rise from Antarctic ice loss in 2025 is strongly predictive of the rate for the next several decades, regardless of emission pathway or model complexity. This finding is robust across all models that were considered in the Intergovernmental Panel on Climate Change Sixth Assessment Report global mean sea-level projections, including the low-likelihood, high-impact scenarios of sea-level rise. Given this strong near-term decadal predictability, ice-sheet models that can accurately reproduce present-day ice-mass loss provide a reliable basis for near-term sea-level planning and adaptation through to mid-century. The predictability breaks down by the end of the twenty-first century as feedbacks, such as those related to marine ice-sheet retreat, begin to emerge, leading to accelerating ice loss. Drawing on these results, we identify key feedback mechanisms that can account for the transition between near-term decadal predictability and the longer-term, feedback-driven evolution, and suggest priorities for ice-sheet model development aimed at resolving long-term sea-level rise uncertainty. Although Antarctic ice loss projections diverge widely by 2100, this Perspective shows that present-day rates robustly predict mid-century sea level rise, providing a firm basis for near-term planning, while highlighting priorities for model development aimed at resolving longer-term sea level rise uncertainty.

22.
Nature (Science) 2026-06-24

The mutational landscape of STING-induced immunity

Authors:

Stimulator of interferon genes (STING) is an evolutionary conserved immune signalling protein with key roles in host defence, cancer, senescence and inflammation1–3. Downstream of STING, type I interferon, inflammatory cytokine signalling and non-canonical autophagy are governed by a multilayered mechanism integrating ligand-induced structural transitions, protein–protein interactions and coordinated intracellular trafficking4–13. Despite its central role in immunity and relevance as therapeutic target14, the sequence elements that govern STING (in)activation in cells remain incompletely understood. Here we developed a massively parallel assay to systematically chart the sequence-function landscape of STING. Profiling thousands of single amino-acid variants, we identified structural and functional determinants that shape the immunostimulatory capacity of STING and its ability to translate ligand recognition into distinct signalling outputs. Cryogenic-electron microscopy structures of select STING hyperactive variants revealed new regulatory principles dictating conformational transition from inactive to signalling-competent states of STING. Mutational effects are widespread across the functional landscape and can sensitize STING towards the natural ligand 2′3′-cGAMP15–18 or decouple interferon induction from non-canonical autophagy, demonstrating a diversity of possible responses that can be accessed through single point substitutions. Finally, our data showed the clinical and evolutionary relevance of naturally occurring STING protein variants. Collectively, these findings define molecular principles that tune STING activity and chart the landscape of its functional potential across immune contexts. A massively parallel assay systematically charts the sequence-function landscape of the STING signalling protein, and the findings define molecular principles that tune STING activity and show its functional potential across immune contexts.

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

Beyond representational alignment with brain-guided language models for robust reasoning

The correspondence between large language models (LLMs) and the neural mechanisms underlying human higher-order cognition remains insufficiently characterized. Given that language and reasoning in the human brain appear dissociable, an open question is whether LLMs align with neural signals from reasoning-related regions and whether such signals can improve them. Here, focusing on deductive reasoning, we show that LLM internal representations are not only partially aligned with task-fMRI activity but can also be directly enhanced by these signals. Using a neural-predictivity metric, we find that LLMs explain a substantial fraction of the explainable variance in reasoning-related regions at the aggregate level, whereas predictivity within specific reasoning types is lower, indicating both alignment and divergence. Building on this, we propose a brain-guided framework: we steer model representations along directions induced by the joint structure of model and brain representations, applying intervention at inference and fine-tuning during training. We demonstrate that task-evoked brain signals can directly enhance LLM reasoning, yielding gains orthogonal to language-only supervision across 10 LLMs (1.5B-72B), with transfer across reasoning types and up to 13\% absolute accuracy gain. Our results advance LLM-brain correspondences from correlation to guidance, establishing a brain-signal-driven pathway toward more robust and cognitively aligned AI.

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

SegTME-UNI2: A Foundation Model-Based Framework for Generalisable Multiclass Cell Segmentation and LLM-Driven Tumour Microenvironment Characterisation in Histopathology

Characterising the tumour microenvironment (TME) from routine H&E-stained histology images requires simultaneous cell segmentation, feature extraction, and interpretable clinical reporting. We present SEGTME-UNI2, a unified framework addressing these requirements. Its core is UNI2-UPERHOVER, a dual-head segmentation model pairing the UNI2-H pathology foundation model (ViT-Giant, pretrained on >100M tiles from 100K slides) with two parallel UperNet decoders: one for six-class semantic segmentation and one for horizontal-vertical gradient regression enabling watershed-based nuclear instance separation. To address the lack of pixel-level annotations in large real-world repositories, UNI2-UPERHOVER undergoes a three-stage progressive pseudo-label curriculum. Each stage trains a fresh model without weight transfer, driving improvement entirely via increased pseudo-label quality: Stage 1: Uses human-annotated PanNuke (7,901 images, 189,744 nuclei, 0.25 um/pixel). Stage 2: Uses entropy-filtered pseudo-labels from the Stage 1 model on 271,711 TCGA-UT scale-0 patches (0.5 um/pixel). Stage 3: Uses pseudo-labels from the Stage 2 model on all 1,608,060 TCGA-UT patches across six resolution scales (0.5-1.0 um/pixel). Segmentation outputs feed a structured TME feature extraction pipeline computing 20+ per-patch compositional, morphological, spatial entropy, and intercellular distance metrics. These are encoded as JSON and passed to a fine-tuned NVIDIA BioNeMo GPT model to generate clinically interpretable TME narratives. Preliminary validation on held-out PanNuke and TCGA-UT partitions demonstrates framework feasibility and internal consistency. The pseudo-labelled TCGA-UT dataset and UNI2-UPERHOVER checkpoint are publicly released to support large-scale TME profiling and spatial biology research.

25.
medRxiv (Medicine) 2026-06-15

Anti-Platelet Factor 4 Antibody Clonal Heterogeneity and MGUS Status in HIT

Background Monoclonal gammopathy of thrombotic significance (MGTS) is a recently described chronic prothrombotic condition characterized by monoclonal anti-PF4 antibodies that are detected above the polyclonal antibody background in patient sera (i.e. present as monoclonal gammopathy of undetermined significance, MGUS). Due to conflicting data in the published literature on antibody clonality in heparin-induced thrombocytopenia (HIT), we evaluated clonality and abundance of anti-PF4 antibodies in HIT, including investigating whether an MGUS, if present in HIT, represents the causative anti-PF4 antibody. Methods Blood samples from 15 patients with HIT were subject to Platelet Factor 4-dependent antigen-based and functional tests. The unmanipulated serum antibody repertoire and isolated anti-PF4 antibodies were subjected to mass spectrometric evaluation. Results Two of the 15 HIT patients had an IgG MGUS. Notably, anti-PF4 antibodies were not synonymous with the MGUS antibody in either of the two patients. Eight of the 15 patients demonstrated monoclonal anti-PF4 antibodies, however, none of the anti-PF4 antibodies were detectable as an MGUS upon evaluation of the entire serum antibody repertoire, reflecting their low abundance. In the seven patients with multiple anti-PF4 antibodies, non-monoclonality was confirmed by analysis of deglycosylated antibody heavy chains. Conclusions Anti-PF4 HIT antibodies are monoclonal in approximately 50% of HIT patients, however, antibody abundance is low such that they are not detectable over the polyclonal IgG background (i.e. are MGUS-negative), differentiating HIT from MGTS. This observation helps explain the transient nature of HIT relative to the persistent prothrombotic state seen in MGTS.