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01.
arXiv (CS.LG) 2026-06-11

Categorical Robustness Assessment for Machine Learning based Network Intrusion Detection Systems

arXiv:2606.12075v1 Announce Type: cross Abstract: Network Intrusion Detection Systems (NIDS) heavily utlize Machine Learning (ML) but ML models can be manipulated via adversarial attacks. These attacks add carefully crafted perturbations to network traffic data that leads to misclassifications. While prior work has demonstrated adversarial vulnerabilities in isolated settings, systematic cross-architecture as well as class and category of attack based comparisons under controlled attack conditions remain limited, leaving practitioners without clear guidance on which models to deploy in adversarial environments. This paper asks a simple question: what type of classifier architectures actually hold up when attackers try to manipulate the systems? We put three popular architectures through their paces: a 1D Convolutional Neural Network, a Long Short-Term Memory (LSTM) network, and a Random Forest (RF) ensemble. Using the ACI-IoT-2023 dataset (over 1.2 million samples spanning 12 attack types), we subject each model with FGSM and PGD adversarial attacks, which apply gradient-based perturbations in normalized feature space consistent with established adversarial ML evaluation protocols, at perturbation budgets ranging from $\epsilon=0.01$ to $\epsilon=0.1$. Surprisingly, Random Forest achieved near-perfect baseline accuracy (99.98\%), yet collapsed catastrophically under attack, dropping 73 percentage points at the smallest perturbation we tested. CNN, on the other hand, retained 95.5\% accuracy at $\epsilon=0.01$ and degraded gracefully as perturbations increased. LSTM fell somewhere in between. These findings flip the conventional wisdom where high baseline accuracy means nothing if a model shatters at the first sign of adversarial pressure. For practitioners deploying intrusion detection in adversarial environments, we recommend CNN-based architectures and provide scenario-specific deployment guidance.

02.
arXiv (quant-ph) 2026-06-16

Reconstruction of detector error model for quantum error correction

arXiv:2606.16288v1 Announce Type: new Abstract: Fault-tolerant quantum computing fundamentally relies on the accurate characterization of circuit-level noise to optimize decoding algorithms. However, extracting complex multi-body error correlations remains challenging. Contemporary greedy inference algorithms can suffer from statistical distortion, discarding true physical mechanisms while introducing many unphysical false positives. Here, we introduce the Correlation-Analysis-based Hypergraph Reconstruction (CAHR) algorithm, a globally consistent framework to invert experimental syndrome statistics directly into discrete physical hypergraphs. By coupling exact algebraic correlation equations with a top-down concurrent-pruning strategy, CAHR recovers the fault topology without false positives for both $d=5$ rotated surface codes and dense 8-body 2D color codes in our benchmark settings. Furthermore, we show that exact continuous parameter extraction in dense codes is limited by a variance cascade, where absolute statistical variance accumulates linearly from high- to low-degree mechanisms. This motivates a two-stage inference paradigm: utilizing CAHR to extract the fault topology, followed by continuous probability optimization. This provides a practical approach for characterizing and decoding highly correlated noise in realistic quantum hardware.

03.
medRxiv (Medicine) 2026-06-22

Leishmaniasis on YouTube: a critical appraisal of the quality, reliability, and transparency of educational content

Background: Leishmaniasis is a neglected tropical disease of significant global public health importance, for which accurate information is essential to support prevention and early care-seeking, particularly in endemic, resource-limited settings. YouTube is a widely used source of health information, but the quality and reliability of leishmaniasis-related content have not been evaluated. We aimed to assess the quality, reliability, and transparency of English-language YouTube videos on leishmaniasis. Methods: We conducted a cross-sectional analysis of YouTube videos retrieved via the YouTube Data API on 15 June 2026 using the terms "leishmaniasis," "cutaneous leishmaniasis," and "visceral leishmaniasis." After applying eligibility criteria and screening the 150 most-viewed eligible videos, 48 videos were included. Two reviewers independently assessed each video using the modified DISCERN (mDISCERN) tool, the Global Quality Score (GQS), and the JAMA benchmark criteria, with disagreements resolved by consensus. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC), and associations were examined using Spearman's rank correlation. Results: Of 402 videos retrieved, 48 met the inclusion criteria. The median GQS was 3.00 (IQR 2.00-4.00) and median mDISCERN was 3.00 (IQR 2.38-4.50), indicating moderate quality and reliability, while the median JAMA score was 2.00 (IQR 1.00-2.00), reflecting limited transparency; no video met all four JAMA criteria. The overwhelming majority of videos (47/48, 97.9%) were of professional or institutional origin. Inter-rater agreement was good to excellent (ICC 0.883 for GQS, 0.896 for mDISCERN, 1.000 for JAMA). The instruments were strongly inter-correlated (mDISCERN-GQS rho = 0.841, p < 0.001). Quality scores did not correlate positively with views, likes, or video duration; comments correlated weakly and negatively with mDISCERN (rho = -0.337, p = 0.031) and JAMA (rho = -0.381, p = 0.014). Conclusions: YouTube videos on leishmaniasis are of moderate quality and reliability but limited transparency, and are produced almost exclusively by professional sources. Video popularity, length, and age were not indicators of quality. There is a need for experts and institutions to produce clearly authored, well-sourced, and transparent educational content on this neglected tropical disease.

04.
arXiv (CS.CV) 2026-06-17

Beware of Aliases – Signal Preservation is Crucial for Robust Image Restoration

Image restoration networks are usually comprised of an encoder and a decoder, responsible for aggregating image content from noisy, distorted data and to restore clean, undistorted images, respectively. Data aggregation as well as high-resolution image generation both usually come at the risk of involving aliases, i.e.~standard architectures put their ability to reconstruct the model input in jeopardy to reach high PSNR values on validation data. The price to be paid is low model robustness. In this work, we show that simply providing alias-free paths in state-of-the-art reconstruction transformers supports improved model robustness at low costs on the restoration performance. We do so by proposing BOA-Restormer, a transformer-based image restoration model that executes downsampling and upsampling operations partly in the frequency domain to ensure alias-free paths along the entire model while potentially preserving all relevant high-frequency information.

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

Branch-and-Browse: Efficient and Controllable Web Exploration with Tree-Structured Reasoning and Action Memory

Autonomous web agents powered by large language models (LLMs) show strong potential for performing goal-oriented tasks such as information retrieval, report generation, and online transactions. These agents mark a key step toward practical embodied reasoning in open web environments. However, existing approaches remain limited in reasoning depth and efficiency: vanilla linear methods fail at multi-step reasoning and lack effective backtracking, while other search strategies are coarse-grained and computationally costly. We introduce Branch-and-Browse, a fine-grained web agent framework that unifies structured reasoning-acting, contextual memory, and efficient execution. It (i) employs explicit subtask management with tree-structured exploration for controllable multi-branch reasoning, (ii) bootstraps exploration through efficient web state replay with background reasoning, and (iii) leverages a page action memory to share explored actions within and across sessions. On the WebArena benchmark, Branch-and-Browse achieves a task success rate of 35.8\% and reduces execution time by up to 40.4\% relative to state-of-the-art methods. These results demonstrate that Branch-and-Browse is a reliable and efficient framework for LLM-based web agents.

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

AthDGC: An Open Diachronic Greek Treebank with Indo-European Parallels

AthDGC ("Athens-PROIEL") is an open, end-to-end workflow and dataset. It is, to the best of our knowledge, the first openly licensed dependency-parsed treebank of Greek that spans eight diachronic periods, namely Archaic, Classical, Koine, Late Antique, Byzantine, Late Byzantine, Early Modern, and Modern Greek, under a single PROIEL XML 2.0 schema, with verse-level cross-alignment of the New Testament to Latin (Vulgate), Gothic (Wulfila), Old Church Slavonic (Marianus), and Classical Armenian. AthDGC builds on the PROIEL Treebank Family (Haug and Johndal 2008; Eckhoff et al. 2018), which established the schema and the Koine-Greek reference set for the project. Annotation uses the Stanford Stanza PROIEL-trained workflow; sentence-level alignment uses LaBSE, a multilingual sentence-embedding model; word-level alignment uses multilingual-BERT attention through the AwesomeAlign procedure. The v0.4 release provides curated samples and the open-source toolkit; the full annotated corpus partitions remain under v0.5 audit on the Greek national HPC. Quantitative scale, per-witness verse counts, and per-period annotated-row counts are reported in the v0.5 release notes, after the audit pass completes. Concept DOI: 10.5281/zenodo.20439182.

07.
arXiv (CS.LG) 2026-06-12

Ride, Track, and Recover: Pilot Randomized Trial of a Wearable Digital Self-Management Intervention During a Veteran Endurance-Cycling Program

arXiv:2606.13529v1 Announce Type: cross Abstract: Post-traumatic stress disorder (PTSD) in veterans is characterized by persistent hyperarousal and comorbid anxiety and depressive symptoms that are difficult to monitor and manage outside clinical settings. Thirteen veterans participating in a Project Hero cycling event in Texas were randomized by computer-generated sequence in a naturalistic setting to two arms: (1) digital intervention plus physical activity, or (2) physical activity only, plus a third at-home monitoring control cohort consisting of 7 veterans selected from the broader Project Hero veteran community. Continuous smartwatch sensing combined heart rate and accelerometer features to detect hyperarousal events, which were confirmed in real time by participants. Weekly self-report measures of anxiety, depression, and PTSD severity were collected. Generalized additive mixed models characterized nonlinear trajectories over time. Baseline-normalized hyperarousal trajectories differed significantly across conditions, with the digital intervention group (n=7) showing structured stabilization compared to late-study escalation in the physical-only group (n=3). Both cycling groups exhibited acute symptom improvements during the endurance event; however, the digital intervention group demonstrated a higher overall maintenance of gains. The at-home control group (n=4) showed gradual symptom declines. Perceived precision of ML detections varied substantially across individuals and was positively associated with symptom severity, with higher-severity participants confirming a greater proportion of detected events. These results suggest that coupling wearable detection with digital self-management tools may support stabilization of hyperarousal and symptom improvement while emphasizing the importance of personalization and human-centered design in wearable mental health systems.

08.
arXiv (CS.CV) 2026-06-11

Exploring Adaptive Masked Reconstruction for Self-Supervised Skeleton-Based Action Recognition

Recently, masked skeleton reconstruction models have emerged as strong action representation learners, driving significant progress in self-supervised skeleton-based action recognition. However, existing state-of-the-art methods must predict an exceedingly large number of spatiotemporal patches, significantly prolonging training time. Besides, by treating all spatiotemporal regions equally during reconstruction, these models are distracted from learning the critical motion patterns that underlie action semantics. To address these challenges, we propose Adaptive Masked Reconstruction (AMR), a faster and stronger pre-training framework. We first decouple the decoder from the encoder, enabling flexible prediction of larger spatiotemporal patches and dramatically reducing reconstruction complexity. Given that larger patches contain more complex information, which is challenging to predict and consequently degrades performance, we accordingly introduce an adaptive guidance module. This module identifies regions of high motion informativeness, guiding the model to focus on the most discriminative parts of each patch and alleviating reconstruction difficulty. Experiments on NTU RGB+D 60, NTU RGB+D 120, and PKU-MMD datasets demonstrate that AMR not only accelerates pre-training substantially but also improves downstream recognition accuracy, surpassing current state-of-the-art approaches.

09.
medRxiv (Medicine) 2026-06-22

Histologically validated diffusion MRI signatures of neuroinflammation and neurodegeneration in Alzheimer disease

Noninvasive neuroinflammation measurement remains a major barrier for Alzheimer disease (AD) therapeutics. We present generalized diffusion basis spectrum imaging (g-DBSI), a diffusion MRI framework that decomposes the tissue signal into biologically interpretable microstructural compartments. In postmortem Knight ADRC brains, g-DBSI-derived restricted isotropic fraction (RIF) and restricted anisotropic fraction (RAF) mapped cellularity and neurofilament density, while their ratio (RIF/RAF) tracked inflammatory cell density and peri-plaque amyloid-beta with higher specificity and regional consistency than RIF alone. In 112 living Knight ADRC participants stratified by PET amyloid, g-DBSI metrics showed amyloid-dependent trajectories: in low-amyloid individuals, RIF and RAF rose together with amyloid, consistent with early neuropil expansion and glial elaboration, whereas in high-amyloid individuals, RIF/RAF increased, and RAF declined, indicating established neuroinflammatory remodeling and neurofilament loss. CSF proteomics linked RIF/RAF to glia-enriched immune and vascular pathways, supporting g-DBSI as a clinically compatible MRI biomarker of neuroinflammation and neurodegeneration in AD.

10.
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.

11.
arXiv (CS.CL) 2026-06-16

A Self Consistency Based Reranking for Narrative Question Answering

Narrative question answering (NQA) is a challenging task in natural language processing that requires models to understand long textual contexts, capture relationships across events, and generate coherent responses. Despite recent advances in pretrained language models, most existing approaches rely on a single decoding output during inference, making them sensitive to generation variability and often resulting in incomplete or inconsistent answers .To address this limitation, we propose a self-ensemble Self-Consistency-Based reranking framework for narrative question answering. The proposed method generates multiple candidate answers for each story-question pair and selects the final answer based on semantic agreement among the generated responses. This allows the model to explore diverse answer formulations while improving robustness through consensus-based selection without requiring modifications to the underlying architecture .The framework combines pretrained and fine-tuned language generation with multi-answer inference and similarity-based reranking. We evaluate the proposed approach on the NarrativeQA dataset using multiple models, including FLAN-T5 (Base and Small) and Pegasus-Large, under both baseline and fine-tuned settings .Experimental results demonstrate that the proposed method consistently improves performance across all models. In particular, FLAN-T5-Base achieves the best overall performance, improving from 82.32% to 86.66% (+4.34%) when combined with self-ensemble inference. Additionally, the largest improvement is observed with Pegasus-Large, which increases from 72.50% to 87.07% (+14.57%), highlighting the effectiveness of the proposed strategy.

12.
arXiv (CS.CL) 2026-06-11

Semantic Grading of Written Answers in Low-Resource Language Bangla Using a Fine-Tuned Lightweight Language Model

Bangla is among the world's most widely spoken languages, yet it remains underserved in educational NLP research. In many remote and rural regions, access to qualified subject teachers is limited, and written answers are consequently graded largely by hand, restricting timely and consistent feedback. Automatic assessment is challenging because semantically correct responses can vary substantially in surface form. We present a bilingual (Bangla-English) evaluation system designed for low-resource educational settings that prioritizes semantic correctness over lexical overlap. Our approach fine-tunes a lightweight language model to grade each response using the question, reference answer, and student answer, producing a numeric score and concise, context-grounded feedback suitable for classroom deployment. We also construct a synthetic bilingual dataset to enable controlled training and evaluation. Across proprietary and open-source LLMs evaluated under a unified protocol, our QLoRA-tuned Qwen3-8B confirms consistent improvement by producing the most leakage-resistant feedback (RoRa = 0.819) in synthetic evaluation and the strongest agreement with human scores (rho = 0.936, MAE = 0.725) in a dedicated human study.

13.
medRxiv (Medicine) 2026-06-10

Assessment of the accuracy of lung lesions diagnosis in adolescents with osteosarcoma using artificial intelligence

Background. Lung metastases in osteosarcoma (OS) are the main cause of the death. The accuracy of the diagnosis of nodules by computed tomography (CT) of the lungs is critically important for determining the disseminated stage of the disease and planning surgical treatment. The use of artificial intelligence (AI) in the search for lung nodules increases the accuracy of diagnosis and reduces the chance of missing metastases. Objective: to evaluate the accuracy of lung nodules diagnosis in adolescents with OS using AI. Methods. A retrospective assessment of CT scans of adolescents with OS was performed. A pathological nodule with an average size of [&ge;]4 mm was considered a target finding. The diagnostic accuracy of an AI algorithm previously trained on an adult dataset was evaluated, and the number of false positives (FP) and false negatives (FN) was determined. Sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, and F1-measure were calculated. Based on the obtained results, the effectiveness of the algorithm was assessed. Results. 248 CT scans of adolescents with OS were evaluated. The following results were obtained: in 5 cases, the AI algorithm showed a FP result (2.02%), in 34 cases, it showed a FN result (13.71%), and in 209 cases, a correct result (both true positive and true negative) (84.27%). The diagnostic accuracy of the algorithm was 0.843 (95% CI 0.794-0.887). The application of the AI algorithm in the practice of an X-ray doctor in a specific clinical task would allow to increase the sensitivity from 0.805 to 0.891, while ensuring an absolute decrease in the number of FN results by 8.59% and a relative decrease by 44%. Conclusion. The obtained results confirm the practical value of the application of the AI algorithm and justify the implementation of AI-assisted systems in the diagnostic protocols for lung metastases in adolescents with OS.

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

OneCanvas: 3D Scene Understanding via Panoramic Reprojection

Existing approaches to 3D scene understanding in Vision-Language Models (VLMs) either rely on complex, model-specific geometry encoders or large training budgets in pursuit of spatial reasoning. Instead, OneCanvas aggregates patch features from all views onto a single equirectangular panoramic canvas. Namely, each patch is unprojected to a 3D world coordinate using its depth and camera pose, then placed on the canvas at the continuous longitude and latitude of that point as seen from the canvas origin, with no rasterization or aggregation across overlapping views. A 3D position embedding of the patch's metric coordinates is added to its feature, restoring the depth lost when collapsing the world position to an angular canvas coordinate. Patches from all frames thus share one spatial coordinate system with no fusion or major architectural modifications of the backbone. The pretrained VLM consumes this representation as if it were an ordinary image. Because the canvas can be centered on any pose of interest, the same representation directly supports situated reasoning from a specific viewpoint, a common requirement in robotics and embodied AI. Thanks to this representation, we can also introduce a spatial pretraining curriculum: by procedurally placing patch features of objects, drawn from real images, at chosen 3D world positions on an otherwise empty canvas, we generate on-the-fly supervision spanning a broad range of spatial reasoning tasks, with answer distributions controlled to reduce spatial reasoning shortcuts. OneCanvas achieves state-of-the-art accuracy on SQA3D and VSI-Bench, and generalizes to out-of-distribution data on SPBench, using an order of magnitude less training compute than the strongest competing methods.

15.
arXiv (CS.CL) 2026-06-19

Disentangling Linguistic Relatedness from Task Alignment in Cross-Lingual Transfer

We study cross-lingual transfer by fine-tuning seven large language models (4B–671B parameters) on Arabic and evaluating zero-shot reading comprehension on Semitic languages and non-Semitic controls. Across dense and Mixture-of-Experts architectures, we find no evidence of Semitic-specific transfer: models with weak baselines improve dramatically across all languages, while strong-baseline models show only marginal gains regardless of language family. A chain-of-thought ablation reinforces this finding – the same models that benefit most from fine-tuning benefit equally from inference-time reasoning, suggesting both mechanisms address task-format alignment rather than cross-lingual knowledge transfer.

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

Exact Federated Continual Unlearning for Ridge Heads on Frozen Foundation Models

arXiv:2603.12977v3 Announce Type: replace Abstract: Foundation models are commonly deployed as frozen feature extractors with a small trainable head to adapt to private, user-generated data in federated settings. The ``right to be forgotten'' requires removing the influence of specific samples or users from the trained model on demand. Existing federated unlearning methods target general deep models and rely on approximate reconstruction or selective retraining, making exactness costly or elusive. We study this problem in a practically relevant but under-explored regime: a frozen foundation model with a ridge-regression head. The exact optimum depends on the data only through two additive sufficient statistics, which we turn into a communication protocol supporting an arbitrary stream of add and delete requests via fixed-size messages. The server maintains a head that is, in exact arithmetic, pointwise identical to centralized retraining after every request. We provide deterministic retrain-equivalence guarantees, order and partition invariance, two server-side variants, and a Bayesian certificate of zero KL divergence. Experiments on four benchmarks confirm the guarantees: both variants match centralized ridge retraining to within $10^{-9}$ relative Frobenius error and complete each request at orders-of-magnitude lower cost than federated retraining baselines.

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

On-Policy Distillation with Curriculum Turn-level Guidance for Multi-turn Agents

arXiv:2606.15912v1 Announce Type: cross Abstract: Multi-turn agents that plan, invoke tools, and interact with environments offer a promising paradigm for solving complex tasks, yet their capabilities typically rely on very large models whose inference cost is prohibitive in practice.On-Policy Distillation (OPD) is a natural recipe for transferring such capabilities to smaller students, but we find that it suffers a characteristic failure mode in this setting: small student errors compound across turns and push the trajectory out of the teacher's familiar state distribution, so the teacher's supervision becomes least reliable precisely where the student needs it most.We propose Guided On-Policy Distillation (Guided-OPD), a simple yet effective algorithm that mixes teacher- and student-generated turns within each rollout and schedules the teacher's intervention probability along a curriculum that decays to zero.Strong guidance keeps early trajectories close to the teacher distribution and is then gradually withdrawn to recover the purely on-policy regime used at inference.On ALFWorld, ScienceWorld, and WebShop, distilling Qwen3 students from a Qwen3-30B-A3B teacher, Guided-OPD improves Score by 21.1\% and Success Rate by 25.5\% over vanilla OPD on average, with larger gains on smaller students.

18.
Nature (Science) 2026-06-10

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

Authors:

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

19.
arXiv (CS.AI) 2026-06-11

CredibleDFGO: Differentiable Factor Graph Optimization with Credibility Supervision

arXiv:2605.06100v2 Announce Type: replace-cross Abstract: Global navigation satellite system (GNSS) positioning is widely used for urban navigation, but the covariance reported by the GNSS solver is often unreliable in urban canyons. Existing differentiable factor graph optimization (DFGO) methods learn measurement weighting through the solver, but they still use position-only objectives. As a result, the position estimate may improve while the reported covariance remains too small, too large, or incorrectly oriented. We propose CredibleDFGO (CDFGO), a differentiable GNSS factor graph framework that makes covariance credibility an explicit training target. A Weighting Generation Network (WGN) predicts per-satellite reliability weights, and a differentiable Gauss-Newton solver maps these weights to a position estimate and a Hessian-derived posterior covariance. We use proper scoring rules to supervise the East-North predictive distribution end to end. We study negative log-likelihood (NLL), the energy score (ES), and their combination. Results on three UrbanNav test scenes show consistent gains in covariance credibility. Positioning accuracy also improves on the medium-urban and harsh-urban scenes; on the deep-urban scene, both the mean horizontal error and the 95th-percentile error improve. On the harsh-urban Mong Kok (MK) scene, CDFGO-Combined reduces the mean horizontal error from 13.77 m to 11.68 m, reduces NLL from 40.63 to 6.59, and reduces ES from 12.31 to 9.05 relative to DFGO (MAE). Case studies link the MK improvement to better axis-wise consistency, more credible local covariance ellipses, and satellite-level reweighting.

20.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

21.
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.

23.
arXiv (CS.CV) 2026-06-15

SinGeo: Unlock Single Model's Potential for Robust Cross-View Geo-Localization

Robust cross-view geo-localization (CVGL) remains challenging despite the surge in recent progress. Existing methods still rely on field-of-view (FoV)-specific training paradigms, where models are optimized under a fixed FoV but collapse when tested on unseen FoVs and unknown orientations. This limitation necessitates deploying multiple models to cover diverse variations. Although studies have explored dynamic FoV training by simply randomizing FoVs, they failed to achieve robustness across diverse conditions – implicitly assuming all FoVs are equally difficult. To address this gap, we present SinGeo, a simple yet powerful framework that enables a single model to realize robust cross-view geo-localization without additional modules or explicit transformations. SinGeo employs a dual discriminative learning architecture that enhances intra-view discriminability within both ground and satellite branches, and is the first to introduce a curriculum learning strategy to achieve robust CVGL. Extensive evaluations on four benchmark datasets reveal that SinGeo sets state-of-the-art (SOTA) results under diverse conditions, and notably outperforms methods specifically trained for extreme FoVs. Beyond superior performance, SinGeo also exhibits cross-architecture transferability. Furthermore, we propose a consistency evaluation method to quantitatively assess model stability under varying views, providing an explainable perspective for understanding and advancing robustness in future CVGL research. Codes will be available upon acceptance.

24.
arXiv (CS.LG) 2026-06-16

{\alpha}-Fair Insurance Pricing: A Fairness Continuum

arXiv:2606.14898v1 Announce Type: new Abstract: Fairness in insurance pricing remains a long-standing and deeply debated puzzle. On one hand, insurers, driven by profitability considerations, set premiums that differentiate across individual risks to achieve actuarial fairness. On the other hand, insurance serves a critical societal function by pooling risks across a population, motivating cross-subsidization among groups to promote solidarity fairness. The tension between these two competing notions of fairness makes insurance pricing inherently complex, particularly in modern settings where granular data allow for increasingly fine risk differentiation and regulators face growing pressure to protect vulnerable groups. To address this challenge, we propose an $\alpha$-Fair Individual Solvent Premium ($\alpha$-FISP) framework for insurance pricing that explicitly captures the trade-off between actuarial and solidarity fairness while guaranteeing solvency, a fundamental requirement in insurance operations. We formulate the pricing problem as a constrained optimization task, where actuarially fair premiums are adjusted subject to budget constraints on cross-subsidization within each risk class. This formulation naturally yields a family of solutions parameterized by $\alpha$, tracing a continuum between purely actuarial and purely solidarity-based pricing and enabling decision-makers to select an operating point along this fairness spectrum. We derive theoretical guarantees for the proposed framework. Numerical experiments show that $\alpha$-FISP is computationally tractable and aligns well with the U.S. regulatory regimes featuring heterogeneous state-level fairness requirements.

25.
bioRxiv (Bioinfo) 2026-06-11

DyMoTree decodes early cell state transitions and drivers from single-cell transcriptomes using a tree-structured neural network

Inferring early cell fate from single-cell RNA-sequencing data is essential for identifying cellular origins and fate plasticity in development and disease. However, existing methods often fail to exploit tree-structured lineage trajectories, limiting the accuracy and interpretability of fate mapping. Here we present DyMoTree, a computational framework that models cell fate decisions as nonlinear mappings between progenitor and terminal cell states under explicit lineage constraints. By integrating lineage graphs with a tree-structured neural architecture, DyMoTree learns lineage-resolved cell-state transition maps from single-cell transcriptomes, enabling robust inference of early fate bias and identification of fate-specific progenitor substates and driver genes. Across simulations, lineage-tracing experiments, and in vivo systems, DyMoTree outperformed existing methods in resolving early fate biases. Applications to mouse embryogenesis, lung adenocarcinoma progression, and CAR-T immunotherapy revealed regulatory programs underlying developmental and disease-associated transitions. DyMoTree provides a general framework for modeling lineage-resolved cell-state dynamics underlying development and disease progression.