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01.
Science (Express) 2026-05-07

Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design | Science

作者: 未知作者

A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

02.
arXiv (CS.CV) 2026-06-16

Decoupled Object-Centric Video Understanding for Generating Robotic Manipulation Commands

Translating video demonstrations into executable robot commands remains challenging because existing methods often fail to identify which objects are functionally involved in the demonstrated action. As a result, they may generate commands that are linguistically plausible but operationally ambiguous. We propose an object-centric video understanding framework that decouples action recognition from object identification to generate precise, grammar-free manipulation commands. Our approach integrates Temporal Shift Modules (TSM) for efficient spatio-temporal action classification with a novel Object Selection algorithm that identifies task-relevant objects through trajectory-based role classification, blur detection, and overlap minimization. The selected objects are then processed by Vision-Language Models (VLMs) for robust category recognition and zero-shot generalization. Evaluated on a modified Something-Something V2 dataset, our method achieves 86.79\% action classification accuracy and BLEU-4 scores of 0.337 on standard objects and 0.261 on novel objects. These results improve over the strongest task-specific baseline by 80.2\% and 143.9\%, respectively. Larger gains are observed in METEOR and CIDEr, reaching 157.9\% and 171.7\% on novel objects. Across all semantic metrics, our approach consistently outperforms task-specific methods and remains competitive with, or surpasses, large general-purpose VLMs while retaining a modular, object-centric design.

03.
arXiv (CS.LG) 2026-06-16

RepNet: Tackling spectral bias in deep neural networks via parameter reparameterization

arXiv:2606.16575v1 Announce Type: new Abstract: Deep neural networks (DNNs) have achieved remarkable success in scientific computing, yet they often suffer from spectral bias in capturing oscillatory and multiscale behaviors. In this study, we investigate this limitation by examining the failure of shallow ReLU neural networks in fitting high-frequency functions. This observation identifies two important factors in resolving rapid oscillations: the initial slope scale and the distribution of partition points induced by the networks. Motivated by this analysis, we propose RepNet, a reparameterized DNN model for ReLU and tanh networks designed for high-frequency and multiscale problems. The key idea is to reparameterize the weights and biases in the first hidden layer, which enables effective control of the initial slope scale and provides an appropriate distribution of the initial partition points. Furthermore, treating the reparameterized weights and biases as trainable parameters allows the DNN to achieve adaptive frequency scaling during training. In addition, we derive quantitative estimates for the output and slope magnitudes of the reparameterized DNN to guide the initialization of the proposed method. Numerical experiments, including multiscale one- and four-dimensional function approximation, forward and inverse PDE problems in combination with physics-informed neural networks (PINNs), and operator learning, demonstrate that RepNet improves the predicted accuracy of vanilla DNNs in capturing highly oscillatory features with slightly additional computational cost. These results indicate that RepNet provides an effective and flexible approach for overcoming spectral bias and applying DNNs to multiscale problems.

04.
arXiv (quant-ph) 2026-06-11

Recirculating Quantum Photonic Networks for Fast Deterministic Quantum Information Processing

arXiv:2602.11033v2 Announce Type: replace Abstract: A fundamental challenge in photonics-based deterministic quantum information processing is to realize key transformations on time scales shorter than those of detrimental decoherence and loss mechanisms. This challenge has been addressed through device-focused approaches that aim to increase nonlinear interactions relative to decoherence rates. In this work, we adopt a complementary architecture-focused approach by proposing a recirculating quantum photonic network (RQPN) that minimizes the duration of quantum information processing tasks, thereby reducing the requirements on nonlinear interaction rates. The RQPN consists of a network of all-to-all connected nonlinear cavities with dynamically controlled waveguide couplings, and it processes information by capturing a photonic input state, recirculating photons between the cavities, and releasing a photonic output state. We demonstrate the RQPN's architectural advantage through two examples: first, we show that processing all qubits simultaneously yields faster operations than single- and two-qubit decompositions of the three-qubit Toffoli gate. Second, we demonstrate implementations of a measurement-free correction for single-photon loss, achieving up to seven-fold speedups and significantly improved hardware efficiency relative to state-of-the-art architecture proposals. Our work shows that a single hardware-efficient recirculating architecture substantially reduces the temporal overhead of multi-qubit gates and quantum error correction, thereby lowering the barrier to experimental realizations of deterministic photonic quantum information processing.

05.
arXiv (CS.CV) 2026-06-17

ActWorld: From Explorable to Interactive World Model via Action-Aware Memory

Interactive world models aim to simulate environment dynamics under real-time user actions. However, their action vocabulary is largely confined to navigation: most actions correspond to motion (e.g., walk, turn, look around), while interaction with objects in the scene (e.g., pick up plates, open doors, or trigger physical responses) is either absent, restricted to game domains, or relegated to prompt-to-full-video scenarios. The resulting worlds are visually explorable but not truly actionable. In this work, we present ActWorld, an interactive world model that extends prior navigation-centric generators to support mid-rollout object interaction within a chunk-autoregressive framework. We argue that the navigation-interaction gap stems from two bottlenecks. First, a data bottleneck: the lack of human-object interaction data with accurate, dense labels. Second, a memory bottleneck: recency-biased history compression in existing world models discards the event-transition frames that causally determine subsequent object states, leading to an action-forgetting pathology. On the data side, we construct a 100K interaction video dataset, each annotated with per-chunk captions via chain-of-thought reasoning. On the model side, we introduce a hierarchical action-aware memory design that routes history compression by interaction importance, complemented by a persistent memory bank that maintains event-update and object-identity tokens across long rollouts. Experiments show that ActWorld supports both flexible navigation and rich object interaction within a single model, substantially improving interaction fidelity over navigation-only baselines without sacrificing viewpoint control. Project page is available at https://interactwm.github.io/ActWorld.

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

Energy-Efficient On-Device RAG on a Mobile NPU: System Design and Benchmark on Snapdragon X Elite

Retrieval-Augmented Generation (RAG) pipelines are compute-intensive, combining embedding, retrieval, reranking, and large language model (LLM) generation. Running them entirely on-device benefits privacy, latency, and offline use, but the energy cost of CPU inference is a major barrier. We present what is, to our knowledge, the first end-to-end RAG pipeline that runs all neural stages – embedding, reranking, and LLM generation – on the Qualcomm Hexagon NPU of the Snapdragon X Elite. Profiling on a Dell XPS 13 laptop, we compare NPU-accelerated RAG against CPU and OpenCL/Adreno GPU baselines on indexing and query workloads. On indexing, the NPU achieves 9.1x higher embedding throughput and 12.3x less system energy. On a 120-query Wikipedia-passage benchmark, it delivers 18.1x faster LLM prefilling, 4.0x lower end-to-end query latency, and 4.0x less system energy than the CPU baseline; the same workload on the integrated GPU is 1.7x slower than CPU and uses 6.5x more energy than the NPU. A GPT-4.1 LLM-as-judge evaluation finds NPU answer quality on par with CPU and GPU within evaluator noise (mean 9.32 vs. 8.95 vs. 9.03 on a 1-10 rubric), with 86.7% of queries scoring identically across all three backends. On the Snapdragon X Elite / Hexagon class of laptop SoC, the NPU thus enables practical, energy-efficient on-device RAG without quality regression – a sustainable path toward green edge intelligence that we expect to generalize to comparable mobile NPUs (Apple Neural Engine, Intel NPU, MediaTek APU) as their software stacks mature.

07.
arXiv (CS.AI) 2026-06-15

Shift-Invariant Attribute Scoring for Kolmogorov-Arnold Networks via Shapley Value

arXiv:2510.01663v2 Announce Type: replace-cross Abstract: For many real-world applications, understanding feature-outcome relationships is as crucial as achieving high predictive accuracy. While traditional neural networks excel at prediction, their black-box nature obscures underlying functional relationships. Kolmogorov–Arnold Networks (KANs) address this by employing learnable spline-based activation functions on edges, enabling recovery of symbolic representations while maintaining competitive performance. However, KAN's architecture presents unique challenges for network pruning. Conventional magnitude-based methods become unreliable due to sensitivity to input coordinate shifts. We propose ShapKAN, a pruning framework using Shapley value attribution to assess node importance in a shift-invariant manner. Unlike magnitude-based approaches, ShapKAN quantifies each node's actual contribution, ensuring consistent importance rankings regardless of input parameterization. Extensive experiments on synthetic and real-world datasets demonstrate that ShapKAN preserves true node importance while enabling effective network compression. Our approach improves KAN's interpretability advantages, facilitating deployment in resource-constrained environments.

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

Who Flips? Self- and Cross-Model Counterarguments Reveal Answer Instability in LLMs

Standard accuracy benchmarks are designed to test how closely large language models (LLMs) approach correct answers, but are not suitable for testing whether LLMs stick with a correct answer when that answer is challenged by a plausible counter-argument. We introduce a controlled protocol for evaluating answer stability: after a model answers a multiple-choice question correctly, we challenge the model's answer with a coherent argument for an incorrect option and measure whether the model flips. The setup a) isolates argumentative content from overt social pressure and b) varies argument length, self-attribution, and cross-model source. Across seven frontier models and 57 MMLU subjects, flip rates range from 17.5% to 97.3%, revealing large differences in stability that are not captured by accuracy metrics alone. We find that self-attribution consistently increases flip rates (mean +7.1pp, up to +18.7pp). Also, pooling wrong-answer arguments across models and selecting the most effective one per question yields stronger adversarial challenges than relying on any single source model. We further construct MaxFlip, a curated challenge set that amplifies flips by up to +23.6pp over standard self-generated challenges. We release the protocol, challenge records, and MaxFlip to support stability evaluation alongside standard accuracy benchmarks. Materials are available at https://github.com/nafisenik/WhoFlips and https://hf.co/datasets/nafisehNik/WhoFlips.

09.
medRxiv (Medicine) 2026-06-22

Association of Digoxin Use at Norwood Discharge with Fontan Completion: A Study from the Pediatric Heart Network Public Dataset

Background: Digoxin use after the Norwood procedure has been associated with improved interstage survival in hypoplastic left heart syndrome and related conditions. Whether this benefit translates into improved longer-term outcomes through staged palliation remains unknown. We aimed to determine the association of digoxin use at Norwood discharge with transplant-free survival and Fontan completion. Methods: We conducted a retrospective cohort study using the Pediatric Heart Network (PHN) Single Ventricle Reconstruction trial public dataset, including 549 infants enrolled at 15 North American centers between 2005 and 2008. Competing risk analysis was used to evaluate Fontan completion and Cox regression to assess death or transplantation within 6 years after the Norwood procedure. Mixed-effects models compared pre-Fontan hemodynamic and echocardiographic right ventricular indices between patients treated with and without digoxin after accounting for center clustering and adjustment for sex, shunt type, heart failure medications at Norwood discharge, and census block poverty level. Results: The 6-year cumulative incidence of Fontan completion was higher among patients discharged on digoxin than among those not receiving digoxin (82% vs 71%; p = 0.013). Competing-risk analysis accounting for death and transplant demonstrated a greater likelihood of Fontan completion among digoxin users (aHR 1.31; 95%CI 1.09-1.58; p = 0.005), without significant difference in the hazard of death or transplant (aHR 0.78; 95%CI 0.53-1.15; p = 0.208). No significant differences in pre-Fontan hemodynamic or echocardiographic indices were observed between groups. Initiation of digoxin post Stage II procedure was not associated with improved survival or likelihood to complete Fontan. Conclusion: Digoxin use at the time of Norwood discharge was associated with a 30% greater likelihood of Fontan completion by 6 years, without accompanying improvement in transplant-free survival. These findings extend prior observations of improved interstage outcomes associated with digoxin use and suggest that treatment may facilitate progression through staged palliation.

10.
arXiv (CS.CL) 2026-06-19

SAGE-OPD: Selective Agent-Guided Intervention for Multi-Turn On-Policy Distillation

On-policy distillation (OPD) improves student models by training them on trajectories induced by their own policy, making it a promising approach for mitigating exposure bias in agent training. However, most OPD studies focus on single-turn settings, while realistic LLM agents interact with environments over multiple turns. In this regime, early errors can alter future observations and compound across the trajectory, and standard dense token-level OPD becomes brittle, as it may over-penalize semantically valid alternatives, reinforce local degeneracies such as repeated actions, and propagate unreliable teacher supervision on off-distribution histories. We propose SAGE-OPD, a verifier-free selective intervention framework specifically designed for multi-turn OPD. Instead of applying teacher supervision uniformly across all turns, SAGE-OPD first observes environment feedback and uses teacher judgment to decide whether each student response should be skipped or intervened on. To further address compounding errors, SAGE-OPD weights token-level distillation by teacher confidence, reducing the influence of uncertain teacher distributions on corrupted or ambiguous histories. Finally, SAGE-OPD applies loss normalization to preserve the overall loss scale of standard OPD while retaining selective turn-level weighting. Experiments on agent tasks show that SAGE-OPD consistently improves over baselines, achieving up to a 13.3% relative improvement in ALFWorld unseen success rate over standard OPD. Ablation studies further demonstrate that turn-level intervention, teacher confidence weighting, and loss normalization provide complementary benefits. Our results suggest that effective multi-turn OPD should remain on-policy, but teacher supervision should be selectively allocated to turns where intervention is necessary and reliable.

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

MorVess: Morphology-Aware Pulmonary Vessel Segmentation Network

Accurate pulmonary vessel segmentation remains challenging due to the sparse, tortuous, and multi-scale nature of vascular structures, where small branches are easily lost and topology integrity is difficult to preserve under voxel-wise supervision. Existing deep segmentation models primarily optimize binary masks, lacking explicit geometric constraints, thus struggling to recover continuous tubular morphology and fine vascular connectivity. In this study, we introduce MorVess, a morphology-aware segmentation framework that integrates differentiable geometric priors with large-scale foundation model adaptation to achieve fine-grained vascular parsing. MorVess jointly predicts vessel masks, distance maps, and thickness maps, providing explicit supervision for vascular boundaries, centerline consistency, and smooth diameter transitions. A lightweight 2.5D adapter bridges 3D spatial context and 2D SAM representations, while a global-local fusion block aggregates multi-level semantics and geometric cues for high-fidelity topology reconstruction. Across two challenging pulmonary CT benchmarks, MorVess delivers superior Dice, clDice, and HD95 scores, substantially improving small-vessel recovery and global connectivity. These results demonstrate that embedding geometric intelligence into pretrained vision models offers a principled and scalable pathway toward precise vessel analysis and clinically reliable structural quantification. Our source code is available at https://github.com/MaoFuyou/MorVess.

12.
arXiv (CS.AI) 2026-06-18

IOAH3: Importance-Driven Adaptive Spatial Partitioning

arXiv:2606.18280v1 Announce Type: cross Abstract: We present IOAH3 (Importance-Oriented Adaptive H3 partitioning), a computational method for constructing data-driven spatial partitions of geo-referenced observation domains. Standard approaches to spatial aggregation adopt fixed areal units, such as administrative boundaries or uniform hexagonal grids at a single resolution, without regard to the informational content of the underlying observations in each region. This leads to the well-known modifiable areal unit problem: statistical and inferential results depend on the arbitrary choice of partition, and spatially concentrated phenomena are averaged out in coarse cells that obscure fine-scale structure. IOAH3 addresses this by constructing an adaptive partition in three stages: multi-source feature extraction and importance scoring via principal component analysis over road density, POI density, building density, and terrain roughness signals, with population and flood-hazard data entering as auxiliary inputs to cell filtering and spatial smoothness; spatial cell selection via Markov Random Field graph-cut optimisation, which jointly maximises per-cell importance while enforcing spatial contiguity; and data-driven hierarchical refinement of high-importance regions to finer H3 resolution levels, with neighbour-propagated support to avoid isolated fine-resolution islands. The resulting partitions serve as input to spatial inference pipelines and provide a principled resolution of the partition-sensitivity problem prior to any modelling step.

13.
arXiv (CS.CV) 2026-06-15

Toward 360-Degree Indoor Panorama Editing via Tuning-Free Diffusion Model with Refocusing Cross-Attention

Zero-shot text-guided diffusion has significantly advanced image editing; however, its practical usability remains constrained by three persistent challenges: prompt brittleness that requires meticulous prompt engineering, spillover edits that unintentionally affect non-target regions, and failures on small or cluttered objects caused by limited fine-grained supervision in training data. We propose FocusDiff (Target-Aware Refocusing for Tuning-Free Diffusion Editing), a tuning-free framework for precise and region-specific image manipulation based on refocusing cross-attention. Given a target region obtained through automated segmentation or manual selection, FocusDiff applies selective blurring to non-edit areas to guide attention toward the masked region while accurately transferring the object's identity, structure, and appearance to the edited output. Integrated context-preserving modules further ensure background fidelity and global coherence, enabling accurate edits from simple text prompts in a single pass. We also extend FocusDiff to 360-degree indoor panorama editing and demonstrate its effectiveness within virtual reality environments. Extensive experiments on our localized editing benchmark LIMB, comprising 30 multi-object images and 100 annotated examples including challenging small-object cases, show that FocusDiff outperforms existing zero-shot editors in text-image alignment and background preservation, achieving superior precision, photorealism, and usability. The project page is available at https://vdkhoi20.github.io/FocusDiff.

14.
medRxiv (Medicine) 2026-06-15

HPV Self-Sampling in Cervical Screening: A Rapid Review

Introduction Cervical cancer is the fourth largest cause of cancer deaths in women. HPV self-sampling could increase uptake of cervical screening. This rapid review aimed to determine the accuracy, concordance, uptake and acceptability of self-sampling over clinician-collected samples in high income countries. Method We followed Cochrane Rapid Reviews Methods. Top-up of 4 systematic reviews and meta-analyses was performed. Narrative data synthesis was conducted and meta-analysis where applicable. Databases searched were MEDLINE, EMBASE, CENTRAL and clinical trial registries. Risk of bias was assessed using AMSTAR 2, QUADAS, the Cochrane Risk of Bias (RoB), or the Nudelman and Otto, 2020 tool, depending on the study type. Findings The review included 39 studies for accuracy, 38 studies for concordance, 37 uptake and 48 studies for acceptability. Self-sampling has similar accuracy as clinician-collected samples when PCR-based assays are used. The overall agreement of self-sampling and clinician-collected samples was 87.1%(95%CI;85.6-88.6) with a kappa value of 0.70(95%CI;0.67-0.73). Mail-to-all strategies had higher uptake with participation differences of 11.3%(95%CI:8.4-14.2) in the intention-to-treat analysis and 7.7%(95%CI:4.7-10.8) in the per protocol analysis. Self-sampling is acceptable to non-attendees (91%(95%CI;85.3-94.6). Conclusion and Recommendation Self-sampling shows good performance on the four clinical effectiveness indicators of accuracy, concordance, uptake and acceptability.

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

Illumination-Robust Camera-Based Heart-Rate Estimation for Physiological Sensing in Robots

Physiological awareness is important for service, social, and assistive robots that interact with humans in everyday environments. Remote photoplethysmography (rPPG) enables non-contact heart-rate (HR) estimation from an RGB camera, making it a promising sensing modality for robot-mounted vision systems. However, illumination variation remains a major barrier to robust deployment. This paper presents an end-to-end spatial-temporal transformer framework for remote HR estimation on a new dataset with varied illumination. Our estimator integrates PRNet-based 3D face alignment, clip-level illumination augmentation, the Residual Temporal Standardization Module, and controlled hybrid temporal-frequency supervision. The training objective combines a Soft-Shifted Pearson waveform loss with a spectral Kullback-Leibler divergence loss, where a tuned weight ($\mathbf{\beta}$) controls the contribution of frequency-domain heart-rate guidance. Experiments on a static all-level mix protocol covering three illumination levels show that $\mathbf{\beta}=5$ provides the strongest result among the tested beta settings, achieving a best-run HR mean absolute error (MAE) of 0.79 bpm and an HR correlation of 0.982. Compared with the PhysFormer baseline evaluated on our dataset, our estimator reduces HR MAE by 93.6 %, while increasing HR correlation from 0.088 to 0.982, making it usable when illumination varies.

16.
medRxiv (Medicine) 2026-06-12

High coverage, persistent gaps: quality of Antenatal Care and its determinants in Zambia based on the 2024 Demographic and Health Survey.

Abstract Background Evaluating antenatal care (ANC) quality is critical to reducing maternal and neonatal mortality. In Zambia, despite high basic ANC attendance, comprehensive national evidence on the clinical content and quality of services remains limited. This study assessed the coverage of WHO-recommended ANC interventions and identified factors associated with care quality using the latest national data. Methods A cross-sectional analysis was conducted using data from the 2024 Zambia Demographic and Health Survey. The final analytic sample comprised 4,829 women aged 15-49 with a live birth in the preceding 5 years. A composite index of 15 selected, equally weighted WHO-recommended components evaluated clinical assessment, counseling/screening, preventive interventions, and utilization. Survey-weighted Poisson regression estimated adjusted incidence rate ratios (aIRRs) for the count of ANC components received. Results The mean ANC quality score was 12.5 out of 15 (95% CI: 12.4-12.6), and 78.5% (95% CI: 77.0-80.0) of women achieved adequate ANC ([≥] 12/15 components). While individual clinical and counseling coverage generally exceeded 90%, only 47.2% (95% CI: 45.3-49.0) of women initiated care during the first trimester, and just 4.8% (95% CI: 4.1-5.6) achieved [≥] 8 ANC contacts. Maternal education was the strongest and most stable predictor of quality across all models. Compared to no education, higher education was associated with an 8.0% higher expected quality score (aIRR = 1.080, 95% CI: 1.051-1.110). Lower ANC quality was significantly associated with unwanted pregnancies (aIRR = 0.970, 95% CI: 0.956-0.993) and with residence in Western (aIRR = 0.923, 95% CI: 0.897-0.951) and North Western (aIRR = 0.966, 95% CI: 0.937-0.996) provinces. Absence of distance barriers and residence in Eastern, Luapula, and Copperbelt provinces were associated with higher quality scores. Conclusion While average ANC component coverage in Zambia is high, critical gaps persist in early initiation and total contact frequency. Care adequacy is strongly influenced by maternal education, relationship status, pregnancy intention, and regional inequities. These findings underscore the need for interventions targeted at uneducated women, preventing unintended pregnancies, and underserved regions such as Western and North Western Provinces. Keywords: Antenatal care quality, ANC content, Zambia, maternal education.

17.
arXiv (CS.LG) 2026-06-11

MPK: A Compiler and Runtime for Mega-Kernelizing Tensor Programs

arXiv:2512.22219v2 Announce Type: replace-cross Abstract: We introduce Mirage Persistent Kernel (MPK), the first compiler and runtime system that automatically transforms multi-GPU model inference into a single high-performance mega-kernel. MPK introduces an SM-level graph representation that captures data dependencies at the granularity of individual streaming multiprocessors (SMs), enabling cross-operator software pipelining, \rev{fine-grained overlap of computation and communication, and other optimizations that are infeasible under the conventional kernel-per-operator execution model}. The MPK compiler lowers tensor programs into optimized SM-level task graphs and generates fast CUDA implementations for each task, while the MPK in-kernel parallel runtime executes these tasks within a single persistent mega-kernel using decentralized scheduling across SMs. Together, these components provide end-to-end kernel fusion with minimal developer effort, while preserving the flexibility of existing programming models. Our evaluation shows that MPK significantly outperforms existing kernel-per-operator LLM serving systems, achieving up to 1.7$\times$ lower end-to-end inference latency and pushing LLM inference performance close to the limits of the underlying hardware. MPK is publicly available at https://github.com/mirage-project/mirage.

18.
medRxiv (Medicine) 2026-06-12

Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive molecular complexity, profound stromal remodeling, and limited responsiveness to systemic therapies. Although gemcitabine-based regimens remain widely utilized, the molecular pathways that influence treatment-associated biological variation are incompletely understood. The TGF{beta} and JAK/STAT signaling networks are recognized regulators of tumor progression, immune modulation, and therapeutic resistance; however, their genomic architecture in clinically stratified PDAC populations remains poorly defined. Methods: We employed a conversational artificial intelligence-driven analytical framework to investigate TGF{beta} and JAK/STAT pathway alterations in a cohort of 184 PDAC patients. Clinical and molecular data were integrated to generate age- and treatment-stratified cohorts, enabling pathway-level and gene-level analyses according to gemcitabine exposure. Findings generated through AI-assisted interrogation were subsequently evaluated using conventional statistical approaches. Results: TGF{beta} pathway alterations were identified in approximately one-quarter to one-third of tumors across clinical subgroups and demonstrated relatively stable frequencies regardless of age at diagnosis or gemcitabine treatment status. Gene-level analyses revealed that pathway disruption was predominantly driven by recurrent alterations in SMAD4, with additional low-frequency events involving TGFBR1 and TGFBR2. Notably, TGFBR2 mutations were significantly more frequent among late-onset PDAC patients receiving gemcitabine compared with untreated late-onset patients (8.8% vs. 1.4%; p = 0.04), suggesting a potential treatment-associated enrichment. In contrast, JAK/STAT pathway alterations were rare throughout the cohort, with only isolated mutations observed in pathway components including JAK1, JAK2, JAK3, STAT1, STAT3, and related regulatory genes. No significant differences in JAK/STAT alteration frequencies were identified according to age or treatment exposure. Conclusions: TGF{beta} and JAK/STAT pathways exhibit distinct genomic architectures in PDAC. TGF{beta} pathway disruption represents a recurrent feature of disease biology, largely driven by SMAD4 alterations, while TGFBR2 enrichment in gemcitabine-treated late-onset tumors suggests a potential context-specific association worthy of further investigation. Conversely, genomic alterations within the JAK/STAT pathway are uncommon, indicating that pathway activity may be regulated predominantly through non-genomic mechanisms. These findings demonstrate the utility of conversational artificial intelligence agents for rapid, scalable, and clinically contextualized pathway interrogation and support future studies integrating multi-omic data to refine precision medicine strategies in PDAC.

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

Beyond the Autoregressive Horizon: A Comprehensive Survey of Diffusion Models, World Modelling, and State Space Models for Code

arXiv:2606.23690v1 Announce Type: cross Abstract: Autoregressive (AR) language models have driven significant progress in automated software engineering, enabling powerful code generation and assistance systems. However, the next-token prediction paradigm introduces structural limitations for code reasoning, including restricted global planning, challenges in maintaining long-range dependencies, and limited grounding in program execution semantics. Noting the heavy skewness of existing literature towards AR models, we discuss emerging paradigms that could potentially overcome the logic and scaling bottlenecks of next-token prediction by unlocking next-generation architectural capabilities for code intelligence. Specifically, we discuss the potential of Diffusion Models, which generate code via holistic denoising that captures long-range syntactic constraints often missed by AR models. We also discuss Code World Models (CWMs), which simulate execution states to support reasoning, and State Space Models (SSMs), which provide linear-time efficiency for massive contexts. By connecting these developments with findings from cognitive neuroscience, we outline directions for developing "System 2" code generation agents.

20.
arXiv (CS.CL) 2026-06-18

Graph-ESBMC-PLC: Formal Verification of Graphical PLCopen XML Ladder Diagram Programs Using SMT-Based Model Checking

PLCopen XML defines two encoding formats for IEC 61131-3 Ladder Diagram programs: a textual encoding using elements, and a graphical encoding that represents rung logic as a directed graph of localId/refLocalId connections. ESBMC-PLC supported the textual format but parsed graphical exports from CONTROLLINO, Beremiz, and OpenPLC Editor into an empty GOTO intermediate representation, causing vacuous verification success. This paper presents Graph-ESBMC-PLC, which closes this gap with a DFS-based graphical LD resolver. The resolver traverses the connection graph from leftPowerRail to each coil, extracts rung paths as Boolean contact conjunctions, and applies a three-tier I/O inference scheme. Ordering coils by rightPowerRail connectionPointIn sequence ensures SET coils process before RESET coils, matching IEC scan-cycle semantics. The graphical-to-IR conversion leaves the ESBMC backend unchanged. Validation on 3 graphical LD programs from CONTROLLINO/OpenPLC Editor shows all produce full GOTO IR with nondeterministic inputs and rung logic, versus the empty IR previously. All 3 verify SAFE at k=2 under 70ms. The 11 textual LD benchmarks are fully preserved, with no regression. Two Beremiz examples with no LD content or unsupported timer semantics are reported as discovered limitations. Artifact at Zenodo (DantasCordeiro2026graphical, doi:10.5281/zenodo.20699856).

21.
arXiv (CS.LG) 2026-06-19

Full-Self Diagnostics (FSD): Physics-Grounded Visual Biomarker Inference from Smartphone Video via Inverse Problems and Operator Learning

arXiv:2606.19372v1 Announce Type: cross Abstract: We present Full-Self Diagnostics (FSD), a unified mathematical framework for recovering latent physiological states from unconstrained 9-second facial videos captured by consumer smartphones. The approach integrates five mutually reinforcing components: (1) a physics-based forward model derived from the radiative transfer equation and chromophore absorption that maps camera observables to biomarker concentrations; (2) an information-theoretic observability theory proving that multi-channel visual signals (spectral, pulse, respiratory, micro-expression, and oculomotor) contain strictly increasing mutual information with physiological state; (3) a stable, Tikhonov-regularized inverse problem with domain-uniform identifiability guarantees; (4) an operator-learning formulation that enables generalization across devices, resolutions, and populations; and (5) a supervised learning procedure, interpretable as stochastic variational inference, that continuously refines the model from paired biosensor ground truth with performance improving proportionally to one over the square root of the number of paired observations. Empirical validation on 38812 real-world paired scans across 59 subjects demonstrates practical performance. Self-collected data from the lead author (glucose range 35-550 mg/dL) yields MARD of 29.86 percent with 97.57 percent of predictions in Clarke Error Grid Zones A+B and only 0.27 percent in the dangerous Zone E. A well-managed diabetic participant achieves MARD of 17 percent in the narrower 70-180 mg/dL band. These results confirm that consumer-grade facial video encodes sufficient structured information for clinically relevant, non-invasive biomarker inference under fully unconstrained conditions, with performance scaling predictably as more paired data becomes available.

22.
arXiv (CS.LG) 2026-06-12

Adaptive Weighted Averaging

arXiv:2606.12763v1 Announce Type: new Abstract: We study the problem of selecting the largest among $n$ unknown values $x_1,\dots,x_n$ given only a single unbiased estimate $y_i$ for each $x_i$. We design strategies that are simultaneously admissible (not uniformly dominated by any other strategy) and also never worse than a given baseline such as uniform random selection. We provide an application to stochastic optimization, where we obtain online-to-batch conversion bounds with a desirable "no-compromise" guarantee: they are never worse than standard random iterate selection, and yet can be significantly better in benign settings.

23.
medRxiv (Medicine) 2026-06-16

Sleep regularity outweighs sleep duration as a predictor of disease

Sleep regularity, the consistency of sleep-wake timing from one day to the next, is more strongly associated with longevity than adequate sleep duration. Whether this relationship persists across common diseases is unknown. We compared sleep regularity vs. sleep duration as risk factors for 199 diseases and disorders, using ten million hours of objective sleep-wake data (N=60,998, age[mean{+/-}SD]=62.8{+/-}7.8, 55% female). Multivariable-adjusted risks of incident diseases/disorders for regular/irregular and short/adequate sleepers were compared across 9.5 years of follow-up. Irregular sleep predicted risks for 131 diseases/disorders, more than double the number predicted by short sleep duration (63). Irregular sleep was a superior predictor than short sleep duration for 90 diseases/disorders, including circulatory, metabolic, digestive, renal, infectious, neurological, and musculoskeletal conditions, and mental disorders, whereas short sleep duration was the superior predictor for only 9 diseases/disorders. For models where short sleep duration explained disease risks, 83% were improved by adding sleep regularity. Sleep regularity was a stronger predictor of diseases/disorders than sleep duration in this cohort and should be considered an essential dimension of sleep health.

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arXiv (CS.CL) 2026-06-12

MARD: Mirror-Augmented Reasoning Distillation for Mechanism-Level Drug-Drug Interaction Prediction

Mechanism-level drug-drug interaction (DDI) prediction requires identifying which enzyme or pharmacodynamic axis is implicated, in which direction, and with which evidence – not merely whether two drugs interact. We introduce a reproducible mechanism-level DDI labelling and evaluation protocol with a structured 7-family/147-subtype taxonomy, leakage-safe cold-split protocols, and auditable reasoning metrics for evaluating pharmacological prediction beyond flat interaction classification. We propose a pipeline that produces a 7B reasoning MARD (Mirror-Augmented Reasoning Distillation), combining three training innovations: a single-token KL divergence on direction tag that ties the model's prediction, per-loss PRM-weighted DPO with programmatic hard negatives, and a leakage-safe mechanism-aware retrieval channel. Process-reward step labels are automatically verifiable against DrugBank-structured fields, requiring no human or LLM judges. On the April-2026 DrugBank release, our MARD-7B is the only system in a 32-system comparison whose accuracy survives drug-pair novelty, beating the best baseline by +13.9 pp and GPT-4o by +6.7 pp at ~1% of frontier API cost. Further analysis reveals an anti-memorisation signature where accuracy improves on rarely seen drugs, suggesting that gain comes from structured pharmacological reasoning rather than drug-frequency memorisation. We release corpus, DDI-PRM, retrieval index, and training code.