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01.
arXiv (CS.CL) 2026-06-24

PORTER: Language-Grounded Event Representations for Portable Structured EHR Foundation Models

Most electronic health record (EHR) foundation models encode clinical events as discrete event tokens from a fixed vocabulary and therefore cannot directly represent events containing unseen concepts or new combinations of concepts and attributes such as numeric values. This limits transfer across institutions and even across deployment pipelines within the same institution. We introduce PORTER, a language-grounded structured EHR foundation model that decouples event representation from this fixed vocabulary. PORTER represents events through their descriptions using a frozen text encoder, integrates numeric values through a dedicated pathway, and learns clinical dynamics over patient timelines with an autoregressively pretrained temporal backbone. Across 74 clinical prediction tasks at a pediatric hospital, PORTER matched the mean AUROC of a fixed-vocabulary model with the same temporal backbone and pretraining objective. When the same patient timelines were rendered using event descriptions not seen during pretraining, PORTER transferred without retraining or vocabulary mapping, recovering 97.1% of the mean AUROC of a model trained directly on the target vocabulary. When transferred to MIMIC, PORTER outperformed the fixed-vocabulary model, which dropped 69% of events because their tokens were unseen. Mechanistic analyses showed cross-vocabulary transfer tracked preservation of patient-level representation geometry rather than the scale of the text encoder, and the numeric pathway improved sensitivity to magnitude without disrupting clinical concept identity. PORTER also achieved higher AUROC than a task-specific text serialization comparator, at 329-fold lower amortized compute. PORTER is a step toward vocabulary-independent EHR foundation models that reduce the need for vocabulary harmonization while preserving in-domain performance and enabling efficient cross-task reuse.

03.
arXiv (CS.AI) 2026-06-19

What Do Safety-Aligned LLMs Learn From Mixed Compliance Demonstrations?

arXiv:2606.20508v1 Announce Type: new Abstract: Prior work has shown that in-context demonstrations can jailbreak language models, but it remains unclear how models interpret different types of compliance demonstrations. We study this by mixing benign compliance demonstrations (non-harmful request, helpful response) with harmful compliance demonstrations (harmful request, helpful response) and testing three hypotheses about how demonstration composition drives harmful compliance. Across four models, we find that benign and harmful demonstrations are not interchangeable: benign demonstrations can either reduce or increase harmful compliance depending on the model. We further show that preference optimization is the critical training stage that prevents benign demonstrations from increasing harmful compliance, that demonstration ordering exhibits strong recency bias, and that models differ in how refusal interacts with in-context learning: some adopt demonstrated formatting even when refusing, while others override all in-context signals upon refusal. Taken together, this work moves beyond showing that demonstration-based jailbreaking works to characterizing how it works: what models extract from compliance demonstrations depends on demonstration content, ordering, and training methodology.

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

FLUX3D: High-Fidelity 3D Gaussian Generation with Diffusion-Aligned Sparse Representation

arXiv:2606.24874v1 Announce Type: cross Abstract: Sparse voxel representation has emerged as a scalable foundation for image-to-3D Gaussian Splatting (3DGS) generation, yet current methods struggle to preserve high-frequency visual details of input images due to two structural bottlenecks. First, they adopt discriminative 2D features optimized for semantic abstraction to construct sparse voxel latents, which suppress reconstructive cues and induce a representation bottleneck. Second, in the generation stage, standard diffusion transformers lack effective mechanisms to align dense 2D image tokens with sparse 3D voxel latents, resulting in a cross-modal correspondence bottleneck. To address these issues, we propose FLUX3D, a scalable image-to-3DGS framework that boosts both representation learning and cross-modal alignment during generation. We first revisit 2D feature selection for sparse-voxel-based 3D representation learning, propose Diffusion-Aligned Structured Latents (DA-SLAT) and couple it with a decoder-only architecture to improve 3DGS reconstruction fidelity. We also design a sparse-structure-aware diffusion framework, which integrates the Sparse-structure Multimodal Diffusion Transformer (SMDiT) and Modal-Aware Rotary Positional Embedding (MARoPE) to achieve geometry-agnostic 2D-3D alignment. Extensive benchmark experiments demonstrate that FLUX3D yields substantial improvements in appearance fidelity and significantly outperforms all state-of-the-art (SOTA) methods in generating high-quality 3DGS assets.

05.
arXiv (CS.CV) 2026-06-15

Gaze Heads: How VLMs Look at What They Describe

How a vision-language model internally solves the task of describing an image is far from obvious. We find that the model develops a specific mechanism for this: a small set of attention heads in its language-model backbone, which we call gaze heads, whose attention tracks the image region the model is currently describing. We find them with a simple correlation score from a few forward passes, using comic strips as a controlled testbed where narrative order is laid out spatially. These gaze heads do not just track the image tokens being described: redirecting their attention to a chosen region forces the VLM to describe that region instead. A single attention-mask intervention on the top-100 gaze heads, fewer than 9% of all heads, steers the model's answer to any chosen comic panel at 83.1% accuracy, while the same intervention on random heads fails to redirect the answer, and intervening on all heads destroys generation. The same lever also extends to continuous control: switching the gaze target mid-generation makes the model wrap up its current panel description and move to the new one within a few tokens. Beyond comics, the same intervention redirects answers to chosen regions in natural COCO images. The mechanism further recurs across model sizes from 2B to 32B parameters and across other VLM architectures, although some frozen-encoder families show no comparable head set. More broadly, this shows that targeted edits identified through mechanistic analysis can serve as practical inference-time levers for steering multimodal model behavior, without any retraining. Our code, interactive demo, and datasets are available at https://gaze.baulab.info/

06.
medRxiv (Medicine) 2026-06-16

A MULTICENTER SWEDISH HISTOPATHOLOGY IMAGE DATASET OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS

Refined detection methods, more detailed tumor characterization, and adequate distinction between different pediatric tumor subtypes are necessary to improve diagnosis and treatment, enable precision medicine, and advance patient prognosis. However, the application of computational approaches to pediatric brain tumors remains limited, largely due to the lack of accessible datasets. To address part of this gap, we provide whole slide images (WSIs) of hematoxylin and eosin (H&E)-stained tissue sections from all pediatric central nervous system (CNS) samples collected in Sweden between 2013 and 2023. These data represent a population-based national cohort encompassing all six pediatric oncology centers in Sweden and are available through the Swedish Childhood Tumor Biobank (BTB). The dataset includes 1,446 WSIs of sufficient image quality with confirmed CNS tumor diagnoses, derived from 537 unique subjects (562 cases). In addition, diagnosticrelevant clinical information is included. Corresponding whole-genome sequencing (WGS), wholetranscriptome sequencing (WTS), and methylation array data are available for most tumor samples through separate resources. This H&E dataset has been specifically curated to support artificial intelligence-based analyses, while also serving broader applications in medical research and education. When combined with matched molecular data, it provides a valuable resource for advancing multimodal and precision diagnostic approaches in the pediatric population. Refined detection methods, more detailed tumor mapping and adequate distinction between different subtypes of pediatric tumors are necessary to improve treatment, enable precision medicine and improve patient prognosis. Application of computational algorithms for pediatric brain tumors is very limited mainly due to the unavailability of pediatric histology brain tumor data sets. To enable the development of AI models comprehensive datasets covering a wide range of pediatric brain tumors are needed.

07.
Nature Medicine 2026-06-16

<b>Engineered heart muscle passes early clinical milestone</b>

Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation. Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation.

08.
bioRxiv (Bioinfo) 2026-06-16

Evidence for recombination in dengue virus genomes

Recombination is a key driver of RNA virus evolution, yet its extent and evolutionary implications in dengue virus (DENV) remain incompletely understood. We conducted a comprehensive, genome-wide recombination screen across 6,905 complete DENV genomes representing all four serotypes, 82 countries, and eight decades of sampling (1944-2023) retrieved from the Bacterial and Viral Bioinformatics Resource Center. Using seven complementary recombination detection methods implemented in RDP5, we identified 66 recombination events across 53 unique recombinant sequences, of which 29 are newly described. Events included intra-genotypic (n = 18), inter-genotypic (n = 32), and inter-serotypic (n = 16) exchanges spanning 14 genotypes and four continents, with no meaningful serotype-level enrichment (Cramer's V = 0.054). Recombination was concentrated in non-structural genes, most frequently NS3 (19 events), NS5 (17), and NS2 (12), while the capsid gene contained no recombination events, consistent with strong functional constraint. Single-nucleotide polymorphism analyses confirmed low divergence between recombinants and their inferred parents in both recombinant and non-recombinant regions. Phylogenomic analysis of 6,642 sequences revealed that recombinants cluster significantly closer to their major parents (p = 8.9 x 10-6 ) and that their removal does not significantly alter tree topology (p = 0.898), suggesting that the short length of recombinant regions limits phylogenetic conflict. We also introduce RECOSIM, an unsupervised machine-learning tool for recombination detection that achieved higher precision than RDP5 on both simulated (93.4% vs. 80.0%) and empirical (98.1% vs. 39.3%) datasets. Collectively, these results establish recombination as a widespread, pan-serotypic phenomenon in DENV with implications for genomic surveillance, vaccine evaluation, and evolutionary inference.

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

SCR-Guided Difficulty-Aware Optimization for Infrared Small Target Detection

Infrared small target detection remains challenging due to severe background clutter, low contrast, and weak spatial responses where geometric overlap alone is insufficient to characterize detection quality. In this work, we propose REEM (Reweighted Explicit-visibility Enhanced Modulation), a lightweight SCR-guided difficulty-aware optimization framework that incorporates Signal-to-Clutter Ratio (SCR) as a physically meaningful visibility prior during training. Instead of modifying the network architecture or directly optimizing SCR, REEM computes a ground-truth local SCR from the input image and applies a differentiable modulation to the soft-IoU learning signal, emphasizing low-visibility targets while preserving stable optimization and identical inference behavior. REEM is integrated into a U-Net-based MSHNet without introducing additional parameters, architectural modifications, or inference-time overhead. Extensive experiments demonstrate consistent improvements over the baseline, achieving higher IoU and detection probability (Pd) together with substantially reduced false alarms (FA), particularly under challenging low-visibility conditions. These results suggest that SCR-guided difficulty-aware optimization provides an effective and physically grounded complement to conventional overlap-based objectives for infrared small target detection. The code is available at https://github. com/yall-in-one/Reemm.

10.
arXiv (quant-ph) 2026-06-19

Electrical Noise Produced by Micron-Sized Particles above a Surface Paul Trap

arXiv:2606.19585v1 Announce Type: new Abstract: Electric field noise produced by the surface of ion trap electrodes reduces the fidelity of quantum computing operations. Despite decades of investigation its microscopic origins remain unclear. Here, we measure electric field noise at trapping locations along the symmetry axis of a linear surface Paul trap. We find that noise levels vary by three orders-of-magnitude in one 600$\,\mu$m section of the trap. Optical and scanning electron microscope images show micron-sized particles close to the trapping locations with the highest noise levels. We find that modeling the particles as a lossy dielectric with a effective loss tangent $\tan\theta=0.33(0.06)$ describes the magnitude of the noise, as well as its spatial and frequency dependence. Our observations may explain the large variation of reported noise levels in literature.

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

Predicting the Neutrino Mass Ordering Using Neural Networks

arXiv:2606.03745v1 Announce Type: cross Abstract: Determining the neutrino mass ordering remains a central open problem in particle physics. While next-generation long-baseline experiments are expected to resolve this question, current data provide limited sensitivity because the spectral differences between normal and inverted ordering are subtle and entangled with parameter degeneracies. We investigate a machine-learning strategy for mass-ordering determination using a feed-forward neural-network classifier trained on synthetic long-baseline datasets generated with three-flavour oscillation probabilities, matter effects, and statistical fluctuations. We evaluate the classifier against standard $\chi^2$ and $\log\mathcal{L}$ approaches using common discrimination metrics, including receiver-operating-characteristic curves, to quantify sensitivity and to illustrate how operating points can be selected to prioritise purity or efficiency. We find that the neural network achieves performance comparable to conventional fits for the scenarios studied, providing a flexible, independent cross-check of established analyses. The framework can be extended to incorporate systematic uncertainties and to explore joint inference of oscillation parameters, and it may also serve as a pedagogical tool for introducing machine-learning methods in neutrino physics.

12.
PLOS Medicine 2026-06-16

The data transparency crisis in research: Lessons from systematic reviews and meta-analyses

by Saul Martin-Rodriguez, Rodrigo Fernandez-Gonzalo, David Moher Summary points Systematic reviews and meta-analyses underpin clinical guidelines and health policy, yet their validity may be compromised by limited access to underlying datasets and associated analytical code. Reliance on incomplete or inconsistently reported summary statistics forces researchers to use imputation and unverifiable assumptions, which can distort effect estimates and mislead clinical decision-making. The consequences extend beyond methodology: flawed evidence synthesis can influence treatment recommendations, healthcare spending, and patient safety, as illustrated by historical cases such as hormone replacement therapy. Despite widespread data-sharing policies, compliance remains low, enforcement weak, and monitoring almost non-existent, with many datasets remaining unavailable or inaccessible. This Policy Forum argues for strengthening enforceable data-sharing mechanisms, including clearer enforcement and pragmatic verification approaches within editorial workflows.

13.
arXiv (CS.LG) 2026-06-12

Extracting Governing Equations from Latent Dynamics via Multi-View Contrastive Learning

arXiv:2606.13260v1 Announce Type: new Abstract: Identifying latent dynamical systems from noisy, high-dimensional measurements is a central problem at the intersection of representation learning, system identification, and scientific discovery. We present DYSCO, a multi-view temporal contrastive learning algorithm that jointly recovers latent trajectories and the governing dynamics from such observations, by leveraging multiple independent noisy views of the same underlying process to disentangle signal from noise. By parameterizing the dynamics in a structured functional basis, our framework further enables symbolic recovery of the governing equations within an affine gauge. We offer theoretical guarantees for strong identification up to an affine indeterminacy, extending prior identifiability results to the realistic setting of noisy nonlinear observations. Empirically, we demonstrate accurate recovery of both latent trajectories and flow fields across a diverse set of dynamical regimes (e.g., chaotic, oscillatory, and metastable) under both Gaussian and Poisson observation noise, the latter being particularly relevant for neural recordings.

14.
arXiv (CS.LG) 2026-06-11

Family-Aware Residual Architecture for Predicting Quantum Circuit Simulation Performance

arXiv:2606.11620v1 Announce Type: cross Abstract: Approximate tensor-network simulators enable classical simulation of quantum circuits beyond the reach of exact methods, but selecting optimal approximation parameters – such as bond dimension thresholds – remains a costly trial-and-error process. We present a family-aware neural architecture that predicts both the minimum approximation threshold required to achieve target fidelity and the expected wall-clock runtime for quantum circuit simulation, given only the circuit's OpenQASM description and execution context. Our key insight is that quantum circuits from different algorithmic families (e.g., QFT, Grover, VQE) exhibit fundamentally distinct simulation cost profiles due to their differing entanglement structures. We employ family-conditioned residual corrections – additive, family-specific adjustments atop a shared backbone, drawing on established conditional computation techniques – enabling the model to capture both universal circuit properties and algorithmic nuances. The architecture incorporates a pretrained family classifier (97.5% accuracy) and domain-informed algorithm fingerprint features derived from gate-composition heuristics. Evaluated on circuits spanning 7–130 qubits across 10 algorithm families, our system achieves 79.5% exact threshold accuracy (91.2% within one rung) and $R^2 = 0.82$ runtime correlation, with inference completing in approximately 50 ms – replacing trial-and-error simulation runs that may take minutes to hours. Ablation studies confirm that family-aware modeling provides the single largest performance improvement (+3.2 percentage points), validating the hypothesis that algorithm family is a first-class feature for simulation cost prediction.

15.
arXiv (quant-ph) 2026-06-25

Quantum Error Correction-like Noise Mitigation for Wave-like Dark Matter Searches with Quantum Sensors

arXiv:2511.03253v2 Announce Type: replace-cross Abstract: We propose a quantum error correction-like noise mitigation protocol for enhancing the sensitivity of wave-like dark matter searches with quantum sensors. Our protocol uses multiple sensors to mitigate the noise affecting each sensor individually, allowing for the suppression of excitation noise that is parallel to the dark matter signal. We demonstrate that our protocol can improve the sensitivity to dark matter signals by a factor of $\sqrt{N}$, where $N$ is the number of sensors used, for small $N$. Furthermore, for sufficiently large $N$, we find that our protocol achieves the same performance as the standard quantum limit by the ideal measurement, which non-entangled sensors with parallel noise cannot reach due to the unknown phase of the dark matter field. Our work can be widely applied to various types of signals with unknown phases, and has the potential to enhance the sensitivity of quantum sensors such as arrays of resonant cavities.

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

A Bifurcation Theory Framework for Gradient Descent on the Edge of Stability

作者:

arXiv:2606.15551v1 Announce Type: new Abstract: The Edge of Stability (EoS) phenomenon, where gradient descent operates with sharpness exceeding the classical convergence threshold yet the loss decreases over long timescales, is ubiquitous in modern deep learning but remains poorly understood in realistic settings. Prior rigorous analyses have been largely confined to scalar or low-dimensional losses with specific structural forms. In this work, we develop a bifurcation theory framework for gradient descent on the edge of stability that applies directly to overparameterized neural networks. By decomposing the training dynamics into components normal and tangent to the manifold of minimizers, we show that stable EoS training arises from a flip bifurcation in the normal direction, governed by the sign of the first Lyapunov coefficient, while the tangent dynamics drift toward regions of decreasing sharpness. Under mild spectral and geometric assumptions on the loss landscape, we prove convergence to the minimizing manifold when training at the EoS threshold. As a corollary, we recover and unify prior results: we show that the product-stability condition of Gan (2026) is an instance of our framework.

17.
PLOS Computational Biology 2026-06-23

A novel biclustering algorithm for mining m<sup>6</sup>A co-methylation patterns based on beta-binomial distribution and data screening strategy

作者:

by Zhaoyang Liu, Yuteng Xiao, Dao Xiang, Hao Shi, Kaijian Xia Studies have shown that m6A plays a key role in different life processes such as RNA metabolism, physiology and pathology. However, due to the complexity of life processes, its specific regulatory details are still not revealed. The computational approach based on co-methylation pattern mining of m6A sequencing data can assist in revealing its mechanism and save time and economic cost, however, the current algorithms suffer from the problems of insufficient robustness to low signal-to-noise data and unreliable performance. Based on this, this paper proposes an enhanced beta-binomial distribution biclustering algorithm (EBBM) based on data screening strategy. This algorithm is based on the framework of Bayesian, adopts Gibbs sampling method for parameter inference, and introduces the data screening strategy in the process of parameter inference, which effectively removes the problem that the low signal-to-noise data in the original sequencing data of m6A affects the reliability of the clustering results. The simulation experiment results show that this algorithm can effectively deal with the interference of low signal-to-noise data and accurately mine the co-methylation patterns pre-planted in the data, which is significantly better than the current mainstream biclustering algorithm. In real human m6A sequencing data with 32 samples, this algorithm mined two effective co-methylation patterns, which were enriched to different biological processes, such as negative regulation of phosphorylation and peptidyl lysine methylation, etc. The scoring results of GEO_Score indicate that the results of this algorithm are more biologically meaningful than the clustering results of current mainstream m6A co-methylation pattern mining algorithms.

18.
medRxiv (Medicine) 2026-06-15

Midwifery Practice in Conflict Contexts: Lived Experiences from Somalia and Nigeria

Background: Midwives are a central cadre in the health system, particularly in conflict-affected settings where they are sometimes the primary or even only skilled providers available. Yet, despite their critical role, there is limited qualitative evidence capturing their lived experiences and how these shape workforce entry, retention, and overall well-being. Methods: Drawing on a phenomenological research methodology, this qualitative study was embedded within a larger prospective longitudinal cohort of midwifery students and graduates in Somalia and Nigeria. We conducted focus group discussions with graduate midwives (n=48 in Nigeria; n=63 in Somalia) to explore their experiences transitioning into the workforce and their realities working in health systems impacted by conflict and violent insecurity. Data were analysed using inductive thematic analysis. Results: Five themes emerged from the data: (1) job search and workforce entry, which was described as fraught with challenges and shaped by a set of formal systems in Nigeria but informal networks and structural barriers in Somalia (2) working conditions that were marked by resource scarcity, infrastructural challenges, and heavy and unreasonable workloads, (3) safety, security and coping strategies that differed across the two contexts but reflected persistent exposure to violence and a reliance on ad hoc and personal coping in lieu of systematic protection, (4) community perceptions of midwives, shaped and constrained by social and gender norms and (5) mental health and emotional wellbeing, highlighting stress, burnout and moral injury experienced by this cadre. Conclusion: Our findings highlight the profound challenges faced by midwives working in conflict-affected settings, and they shine a light on the urgent need to support and invest in this critical and predominantly female health workforce.

19.
medRxiv (Medicine) 2026-06-22

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

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

20.
arXiv (quant-ph) 2026-06-19

Quantum Dynamics from Lax Pair Theory: A Reconstruction from Spectrum Preservation

arXiv:2606.19664v1 Announce Type: new Abstract: We reconstruct unitary quantum dynamics from a minimal axiomatic foundation built on Hilbert-space observables and isospectral evolution. The only dynamical assumption is that physical time evolution is a continuous one-parameter flow of Hermitian observables that preserves their spectra, i.e. the possible outcomes of measurement. We show that this assumption is already sufficient to force the Lax form of quantum dynamics. The Heisenberg equation, the time-dependent and time-independent Schrödinger equations, conservation laws, and good quantum numbers then follow as theorems rather than postulates. In this formulation, Lax pair theory supplies the missing dynamical bridge between the measurement structure of a Hilbert space and standard quantum evolution: the Hamiltonian is not assumed, but emerges as the generator required for an isospectral observable flow.

21.
Nature (Science) 2026-06-24

The mutational landscape of STING-induced immunity

作者:

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&nbsp;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&nbsp;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.

22.
PLOS Computational Biology 2026-06-24

The transcriptional gradient in negative-strand RNA viruses suggests a common RNA transcription mechanism

by Connor R. King, Casey-Tyler Berezin, Brian Munsky, Jean Peccoud Nonsegmented negative-strand RNA viruses (NNSV) are a diverse class of medically relevant viruses which display a conserved attenuation gradient in the transcription of their genomes. This gradient has been traditionally explained by the Stop-Start model which attributes attenuation to polymerase behavior at gene junctions. In this article, we evaluate an alternative explanation where the gradient arises from polymerase dynamics during transcription. We introduce the RNA Polymerase Association Mechanism (RAM) model, a coarse-grained stochastic framework that describes transcription using two parameters related to polymerase processivity and the ability of the polymerase to backtrack. The RAM model accurately reproduces transcriptional gradients across diverse NNSVs as well as in gene-shuffled VSV variants. Additionally, the inferred polymerase processivity appears correlated to the length of the viral genomes suggesting a conserved constraint on transcription across these viruses. While the RAM model does not account for all known molecular features of NNSV transcription, it provides a parsimonious and predictive framework for relating genome architecture and transcription. These results support the view that, in tandem with the traditional junction-centric mechanisms governing transcription, nonspecific attenuation mechanisms contribute to the NNSV transcriptional gradient and warrant closer inspection in future studies which could lead to better rational genome design in viral studies and biomedical applications.

23.
arXiv (CS.CL) 2026-06-25

Efficient and Trainable Language Model Test-Time Scaling via Local Branch Routing

Test-time scaling improves language-model reasoning, but existing approaches often face a difficult trade-off: long chain-of-thought sampling remains single-threaded, while sentence- or solution-level search can be computationally expensive and hard to train end-to-end. We introduce Local Branch Routing (LBR), a token-level test-time scaling framework that expands a small local lookahead tree, forwards all sampled branches through the language model, and uses a lightweight router to select the depth-1 subtree to commit. By routing over the hidden states of candidate local futures, LBR allows each token decision to use evidence beyond the root next-token distribution while avoiding full solution-level search. The resulting prune-shift-grow decoding process preserves discrete branch identities and defines a tractable tree-trajectory likelihood: newly grown nodes are counted when first sampled, and router decisions are assigned explicit probabilities. This enables end-to-end reinforcement learning with verifiable rewards, jointly optimizing the base model and router under the same likelihood-ratio principle as discrete-token RLVR. On synthetic hierarchical-planning tasks, LBR shows that post-candidate hidden states provide useful routing evidence. On mathematical reasoning benchmarks, LBR improves both Pass@1 and Pass@32 over discrete chain-of-thought, vanilla discrete-token RLVR, and RL-compatible soft-token branching baselines. These results suggest that lightweight local branching offers an efficient, trainable, and discrete form of language-model test-time scaling.

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

Constructing Evaluation Datasets for Procedural Reasoning: Balancing Naturalness, Grounding, and Multi-Hop Coverage

arXiv:2606.12767v1 Announce Type: new Abstract: Evaluating procedural reasoning in AI-supported learning systems requires question-answer datasets that are both learner-like and grounded in the instructional knowledge the system is expected to use. We study how TMK-based question generation strategies affect dataset quality for procedural and multi-hop reasoning. We compare three strategies: strict generation from Task-Method-Knowledge (TMK) models, transcript-first generation with post-hoc TMK filtering, and TMK-aware generation that combines transcripts with structured guidance. To evaluate generated items, we introduce a grounding validation framework based on closed-set evidence units extracted from TMK models. The framework measures whether answers are supported by the underlying representation, whether questions are self-contained, and whether they target multi-hop procedural reasoning. Across 23 instructional topics and 690 generated question-answer pairs, strict TMK generation achieves the strongest overall quality, with 96.5% grounded questions and 92.6% usable questions. Transcript-first generation produces more learner-like questions but more context-dependent or weakly grounded items, while TMK-aware generation yields high raw multi-hop coverage but lower grounding. These results show that procedural richness and natural phrasing do not guarantee representational grounding, motivating explicit representation-aware validation for evaluation datasets in AI-supported learning.

25.
medRxiv (Medicine) 2026-06-22

Exploring the association of Obesity on Cold and Warm Autoimmune Hemolytic Anemia in San Joaquin Valley: A Retrospective Cross-Sectional Study

The relationship between obesity and specific autoimmune diseases haas been well-established, specifically due to obesity's role in promoting pro-inflammatory states. Although not much literature has been documented regarding obesity association with AIHA. As such, this study aims to assess any correlations in patients with elevated body mass index (BMI) and autoimmune hemolytic anemia (AIHA). Here we present a retrospective cross-sectional study conducted over a four-year period, across four medical centers during which a new electronic medical record was implemented. The study included 25 patients who had a previously documented history of AIHA from another facility, DAT positive with indicators of hemolysis, or DAT positive with monomer specific antisera. The patients BMI was recorded at the time of presentation to the hospital. However, for patients with a prior history of AIHA or those transferred from another facility, the BMI that was closest to the time period of when the patient was diagnosed with AIHA was used as an adjunct. Our results show that there is an association of patients with elevated BMI (>25) and AIHA; however, various other confounding variables should be taken into consideration, and further research should be done to establish a causal relationship.