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

PlaceRep: Geospatial Place Representation Learning from Large-Scale Point-of-Interest Data

arXiv:2507.02921v4 Announce Type: replace-cross Abstract: Learning effective representations of urban environments requires capturing spatial structure beyond fixed administrative boundaries. Existing geospatial representation learning approaches typically aggregate Points of Interest (POIs) into pre-defined administrative regions such as census units or ZIP code areas, assigning a single embedding to each region. However, POIs often form semantically meaningful groups that extend across, within, or beyond these boundaries, defining places that better reflect human activity and urban function. To address this limitation, we propose PlaceRep, a geospatial representation learning method that constructs place-level representations by clustering spatially and semantically related POIs. PlaceRep summarizes large-scale POI graphs from U.S. Foursquare data to produce general-purpose urban region embeddings while automatically identifying places across multiple spatial scales. By eliminating model pre-training, PlaceRep provides a scalable and efficient solution for multi-granular geospatial analysis. Experiments using the tasks of population density estimation and housing price prediction as downstream tasks show that PlaceRep outperforms most state-of-the-art graph-based geospatial representation learning methods and achieves up to a x100 speedup in generating region-level representations on large-scale POI graphs. The implementation of PlaceRep is available at https://github.com/mohammadhashemii/PlaceRep.

02.
arXiv (CS.AI) 2026-06-19

The Tao of Agency: Autotelic AI, Embedded Agency and Dissolution of the Self

Authors:

arXiv:2606.19924v1 Announce Type: new Abstract: Most artificial intelligence systems are built on the assumption that goals are exogenous and specified by the designer. Exploring what happens when an agent begins generating its own goals opens the field of autotelic AI. Agents are expected not merely to pursue objectives but to discover them. In this article, we trace its consequences through intrinsic motivation, resource-driven priors, causal-interventional learning, homeostasis, and embeddedness; the last of which is found to be a necessary but not sufficient condition for autotelic agency. Embeddedness individuates the agent at the cost of revealing that the individuation is non-unique, such that the same dynamics admit many valid partitions, each defining a different candidate self. The deepest problem with autotelic AI is therefore not how the agent generates goals, but how it generates and relativizes the self to which the goals are assigned. The agent must believe in its own boundary in order to act, and see through that boundary in order to understand. We consolidate these developments into a single framework and extend it along three directions: a quantum formulation in which the agent-environment cut becomes physical, a philosophical reading against non-dual contemplative traditions, and a concrete LLM-based agentic instantiation.

03.
arXiv (CS.LG) 2026-06-11

My Chemical Harness: Evolutionary Molecular Design over Synthetic Pathways with Large Language Model Agents

arXiv:2606.11256v1 Announce Type: cross Abstract: Designing molecules with target properties is most useful when candidate structures are accompanied by feasible synthetic routes. We introduce My Chemical Harness, a route-native evolutionary framework for goal-directed molecular design in which the search population consists of executable synthetic pathways rather than isolated molecular graphs. Each route is built from purchasable building blocks and reaction templates, executed by deterministic chemistry tools, and scored through task-specific molecular oracles. Large language models (LLMs) are used only as strategy controllers that select high-level preferences over route length, move type, reaction families, motifs, and exploration pressure, while local code performs route construction, validation, deduplication, scoring, selection, and memory updates. This separation lets the LLM guide exploration without allowing it to introduce hallucinated products or unsupported reaction steps. On a soluble epoxide hydrolase proxy task, our LLM agent improves over single pass LLM and deterministic controllers, reaching state-of-the-art performance across the sEH score, synthetic accessibility score, and AiZynthFinder success rate metrics. These results suggest that constrained LLM agents can play a significant role in molecular discovery without requiring training, fine-tuning, or dedicated generative models.

04.
medRxiv (Medicine) 2026-06-16

Validation of a Smartphone-Image-Based Computer-Vision Model for Lean Mass and Body Fat Estimation Against Dual-Energy X-ray Absorptiometry

Introduction Body composition, rather than body weight alone, is an increasingly important health metric, and preservation of lean mass has become a central concern in obesity treatment, aging, and chronic disease management. Dual-energy X-ray absorptiometry (DXA) provides accurate assessment of fat and lean tissue, but its cost and logistical requirements limit repeated measurement. Computer-vision approaches show promise for estimating adiposity from smartphone images, but lean-mass estimation remains less established. Methods We evaluated a computer-vision body composition model, applied to consumer-grade smartphone photographs, against DXA in a held-out validation sample of 195 adults from an ongoing cross-sectional study. Body fat percentage and total lean mass percentage were co-primary outcomes; for total lean mass percentage, an image-only configuration (no added covariates) was pre-specified as primary. Agreement was quantified using Lin's concordance correlation coefficient (CCC) as the lead statistic, with Pearson correlation, mean absolute error, root mean square error, mean bias, and Bland-Altman limits of agreement. In secondary analyses, appendicular lean mass and total lean mass percentage were each estimated with and without routine anthropometric and demographic inputs (body weight, height, age, and sex). Results Total lean mass percentage agreed with DXA from image features alone (CCC 0.916). Body fat percentage, estimated with routine inputs added, agreed at least as closely (CCC 0.930). Adding routine inputs barely changed agreement for total lean mass percentage but markedly improved it for appendicular lean mass, an absolute quantity that scales with body size. Conclusions A smartphone-image-based model estimated both body fat and lean mass with strong agreement to DXA, with lean mass percentage from image features alone. The approach needs no fixed equipment or ionizing radiation. Whether it can track change over time, including in incretin-based weight loss where lean mass preservation is a concern, was not assessed in this cross-sectional study.

06.
arXiv (math.PR) 2026-06-15

Asymptotic analysis of the normal inverse Gaussian cumulative distribution

Authors:

arXiv:2509.05664v2 Announce Type: replace-cross Abstract: Using a recently derived integral in terms of elementary functions, we derive new asymptotic expansions of the normal inverse Gaussian cumulative distribution function. One of the asymptotic representations is in terms of the normal Gaussian distribution or complementary error function.

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

CausalMotion: Structured Physical Reasoning as Keyframe and Trajectory Guidance for Training-Free Video Generation

Recent advances in diffusion-based video generation have significantly improved visual quality and short-term temporal coherence. However, existing methods still struggle to produce videos with physically consistent and causally plausible dynamics, especially in scenarios involving long-horizon interactions. This limitation arises from the fact that video diffusion models primarily learn physical consistency implicitly, while vision-language models can directly model physical laws. Based on this idea, in this work, we propose CausalMotion, a training-free framework that injects explicit physical reasoning into video generation through structured intermediate representations. Our key idea is to decouple reasoning from generation by leveraging a vision-language model to decompose a text prompt into a sequence of causally consistent keyframes and object-centric motion trajectories. These representations are then aligned and integrated as soft constraints to guide a pretrained video diffusion model during inference. This design enables explicit modeling of object dynamics and causal transitions without requiring additional training or supervision. Extensive experiments show that our method consistently improves physical plausibility and temporal coherence, particularly in dynamics-intensive scenarios, while maintaining high perceptual video quality.

08.
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.

09.
medRxiv (Medicine) 2026-06-17

Investigating shared genetic overlap of immune-mediated inflammatory diseases and cardiometabolic diseases

Abstract Background: Immune-mediated inflammatory diseases (IMIDs) are associated with increased risk of cardiometabolic diseases. Investigating genetic overlap among these conditions can provide insights into their clinical management. Methods: Genetic correlation was assessed using linkage disequilibrium score regression (LDSC). Then, a meta-analysis was conducted using Association Analysis Based on SubSETs (ASSET) to pinpoint independent single nucleotide polymorphisms (SNPs) shared across the diseases. Each independent SNP was then used to define a genomic window (+/-500KB) for colocalisation analysis and Local Analysis of [co]Variant Association (LAVA) to offer multiple layers of regional pleiotropic evidence. Over-representation analysis was then run to identify enriched biological pathways, which then were used for drug target analysis. Results: The LDSC analysis showed a significant global genetic correlation for rheumatoid arthritis (RA) and cardiometabolic diseases including hypertension, coronary artery disease (CAD), heart failure (HF), stroke, atrial fibrillation (AF), and type two diabetes mellitus (T2DM) ranging from rg = 0.09 to 0.24. ASSET meta-analysis identified 164 independent SNPs shared across RA and the cardiometabolic diseases with P < 5 x 10- in the overall one-sided meta-analysis P-value, FDR < 0.05 in both individual GWASs, and TRUE phenotype matrix. Colocalisation analysis revealed multiple loci with strong evidence (Posterior probabilities [&ge;] 80) of single causal SNPs between the trait pairs. LAVA analysis was then used as an additional layer of confirmation for the findings generated by ASSET and colocalisation and thus several loci were highlighted. Over-representation analysis showed significant enriched immune-related pathways across RA-hypertension, RA-CAD, RA-AF, and RA-T2DM trait pairs. Drug target analysis highlighted several drugs which could be further tested for their effectiveness in RA and its common comorbidities. Conclusion: The findings revealed a shared genetic architecture and key immune-related biological pathways underlying RA and its associated cardiometabolic comorbidities. The identified genes and drugs provide opportunities for further therapeutic assessment which could improve clinical management strategies.

10.
arXiv (CS.CV) 2026-06-16

EdgeZSAD: Practical Zero-Shot Anomaly Detection on Edge Devices

Industrial inspection needs zero-shot anomaly detection (ZSAD) that remains useful under edge deployment constraints. Recent methods often rely on ViT-L foundation backbones (~300M parameters), which exceed the memory and operator budget of typical embedded hardware. We study this regime through EdgeZSAD, a compact reference system built around a TinyViT-21M-512 backbone, an asymmetric global-local readout (EdgeGLR), and a reproducible source-side training recipe (Real-IAD-DR). We train a single checkpoint in a source-trained, target-unseen protocol and evaluate it across six industrial benchmarks. Across three independent runs, the resulting model reaches an average image AUROC of 91.6 on MVTec-AD and 88.2 on VisA, while remaining directly deployable on Jetson Orin Nano Super (TensorRT FP16) and RB5 Gen2 (QNN GPU FP16). Across the six device-rescored benchmarks, image-AUROC drift stays below 0.2 points, indicating that the exported graph preserves host-side ranking behavior in the evaluated deployment setting.

11.
medRxiv (Medicine) 2026-06-15

Quantitative Gait Categorization in Parkinson's Disease with and without Freezing of Gait

Background: Freezing of gait (FOG) is a disabling and often underrecognized feature of Parkinsons disease (PD). Objective gait analysis may improve characterization of this motor symptom. Objective: To compare quantitative 3D gait parameters in PD with FOG (PDF) and PD without FOG (PDNF) in a routine clinical cohort. Methods: We retrospectively analyzed a sequential sample of 180 patients with PD referred for motion analysis between 2020 and 2024. All patients underwent 3D motion capture in the off-medication state. Eighteen gait outcomes spanning pace, rhythm, postural control, variability, and asymmetry domains were derived from steady-state walking tasks. FOG status was determined using physician documentation and Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS-UPDRS) items. Group differences between PDF (n=99) and PDNF (n=81) were evaluated using independent samples t-tests, with outcomes adjusted for disease duration and corrected for multiple comparisons. A secondary analysis among PDF compared those in Hoehn and Yahr (H&Y) stage [&ge;]III to those in H&Y [&le;]II. Results: PDF had longer disease duration, higher OFF MDS-UPDRS III scores, and higher Hoehn and Yahr stage than PDNF but were similar in age and sex. After adjusting for disease duration and multiplicity, PDF demonstrated reduced step length, stride length, and forward velocity, and greater cadence variability, while most postural control, and asymmetry measures were comparable between groups. Among PDF, advanced H&Y stage was associated with impaired pace and rhythm, similar to previous reports among PD in general. Conclusion: In this large, sequential, clinically referred cohort, FOG was associated with more advanced PD and specific impairments in pace and gait variability. These findings support comprehensive 3D gait analysis as an objective tool to better delineate FOG-related gait abnormalities and identify features that may predict FOG, informing targeted interventions.

12.
arXiv (quant-ph) 2026-06-12

Multi-entropy in heavy local quenches

arXiv:2606.12526v1 Announce Type: cross Abstract: We study the time evolution of tripartite entanglement in heavy local quenches in two-dimensional holographic conformal field theories. Our diagnostic is the genuine multi-entropy of adjacent intervals, computed from both bulk and boundary perspectives. A perturbative bulk analysis shows that the first-order small-mass perturbation around the vacuum geodesic network cancels identically at any time after the quench. In the fully back-reacted geometry, a vacuum-subtracted genuine multi-entropy arises from a mismatch between the winding selected by the trivalent geodesic network and the windings selected independently by the pairwise geodesics. In the sharp quench limit, the time dependence of genuine multi-entropy is kinematically fixed to logarithms of rational functions of time and is independent of the heavy operator dimension. The CFT calculation reproduces the same formula within the heavy-light vacuum block approximation, where the branch choice in the heavy-background uniformization map corresponds to the winding selection in the bulk. These results indicate that, in this setup, the genuine multi-entropy is controlled by global saddle selection, rather than by a local energy response or quasiparticle propagation.

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

A2D2: Fine-Tuning Any-Length Discrete Diffusion for Adaptive Decoding

arXiv:2606.13565v1 Announce Type: new Abstract: Discrete diffusion models offer a simple and stable likelihood-based framework for sequence generation, recently extended to any-length settings via token insertion. Principled reward-guided fine-tuning for any-length discrete diffusion, however, remains largely unexplored. We introduce Fine-Tuning Any-Length Discrete Diffusion for Adaptive Decoding (A2D2), a unified framework for reward-guided fine-tuning of any-length discrete diffusion models via joint optimization of the insertion and unmasking policies together with a quality-based inference schedule. We derive the Radon-Nikodym derivative for the joint insertion-unmasking path measures, enabling theoretically guaranteed convergence to the intractable reward-tilted sequence distribution without requiring target samples. Building on this, we establish unmasking and insertion quality as tractable approaches for minimizing decoding error and introduce the Adaptive Joint Decoding (AJD) loss, which provably yields the optimal path measure that generates the reward-tilted distribution. Empirically, A2D2 improves reward optimization while enhancing generation flexibility and accuracy over prior fixed-length fine-tuning and inference-time guidance methods.

14.
arXiv (CS.AI) 2026-06-19

KG-SoftMAP: Soft Knowledge-Graph Priors for Bayesian Network Structure Learning from Sparse Discrete Data

arXiv:2606.10358v2 Announce Type: replace-cross Abstract: Learning Bayesian network (BN) structure from sparse discrete data is hard: when each instance records only a few variables, most variable pairs lack the joint observations needed for reliable scoring, and data-only methods recover little structure. However, imperfect domain knowledge, expressible as a weighted directed knowledge graph (KG), is often available. We propose KG-SoftMAP, which encodes such a KG as a finite-strength, confidence-weighted edge prior and maximizes a MAP objective combining the BDeu score with a logit-form prior; the KG may be expert-curated or LLM-extracted. On synthetic benchmarks with known DAGs, KG-SoftMAP reaches Directed-F1 (DF1) $0.19$–$0.32$ at observation rate $\rho=0.05$ and DF1 $0.44$–$0.97$ at $\rho\geq0.2$, while every data-only learner tested stays near zero under the same sparse masks. Recovery tracks KG quality: controlled corruption degrades it smoothly, a zero-signal KG yields DF1 $0.00$, and a blindly LLM-extracted KG with imperfect precision and recall still drives substantial recovery. On three real sparse educational datasets, the learned BN acts as a concept-level posterior model: on SAF it matches logistic regression (LR) within $0.03$ F1_FAIL while providing an inspectable concept graph, calibrated Fail probabilities, and tractable posterior queries from partial observations.

15.
arXiv (CS.LG) 2026-06-12

Generative Modeling of Bach-Style Symbolic Music: A Comparative Study of Autoregressive, Latent-Variable, and Adversarial Approaches

arXiv:2606.13626v1 Announce Type: cross Abstract: We study generative modeling of Bach-style symbolic piano music using a shared MIDI corpus and three model families: autoregressive LSTMs with attention, latent-variable models including recurrent VAEs and vector-quantized VAEs, and generative adversarial networks. We compare their ability to model polyphonic note sequences, learn useful latent representations, and generate stylistically coherent compositions. Our experiments show that the autoregressive LSTM with attention produces the most musically coherent samples, while vector quantization helps mitigate posterior collapse and yields more structured outputs than conventional recurrent VAEs. The adversarial approach captures local pitch patterns but remains difficult to train and generalizes less reliably to Bach's style. These results highlight the relative strengths and failure modes of autoregressive, latent-variable, and adversarial approaches for symbolic music generation.

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

HyperPotter: Spell the Charm of High-Order Interactions in Audio Deepfake Detection

arXiv:2602.05670v2 Announce Type: replace-cross Abstract: Advances in AIGC technologies have enabled the synthesis of highly realistic audio deepfakes capable of deceiving human auditory perception. Although numerous audio deepfake detection (ADD) methods have been developed, most rely on local temporal/spectral features or pairwise relations, overlooking high-order interactions (HOIs). HOIs capture discriminative patterns that emerge from multiple feature components beyond their individual contributions. We propose HyperPotter, a hypergraph-based framework designed to capture high-order relations associated with synergistic patterns through clustering-based hyperedges with class-aware prototype initialization. Extensive experiments on 13 test sets show that HyperPotter improves over the baseline on 11 sets, yielding an average relative EER reduction of 12.68\% across all test sets and 22.15\% on the improved sets. These results demonstrate strong cross-scenario generalization, while also revealing robustness limits under severe codec or channel distortion.

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

Active Sampling for Ultra-Low-Bit-Rate Video Compression via Conditional Controlled Diffusion

Diffusion models provide a powerful generative prior for perceptual reconstruction at ultra-low bitrates, but effective video compression requires controlling the generative process using highly compact conditioning signals. In this work, we present ActDiff-VC, a diffusion-based video compression framework for the ultra-low-bitrate regime. Our method partitions videos into variable-length segments, transmits keyframes only when needed, and summarizes temporal dynamics using a compact set of tracked point trajectories. Conditioned on these sparse signals, a conditional diffusion decoder synthesizes the remaining frames, enabling perceptually realistic reconstruction under severe rate constraints. To support this design, we introduce two mechanisms: content-adaptive keyframe selection and budget-aware sparse trajectory selection, which together enable compact yet effective conditioning for generative reconstruction. Experiments on the UVG and MCL-JCV benchmarks show that ActDiff-VC achieves up to 64.6\% bitrate reduction at matched NIQE, improves KID by up to 64.6\% and FID by up to 37.7\% at comparable bitrates against strong learned codecs, and delivers favorable perceptual rate–distortion trade-offs relative to learned and diffusion-based baselines in the ultra-low-bitrate regime.

18.
PLOS Computational Biology 2026-06-22

Ten simple rules for making the supplement increase your paper’s impact

Authors:

by Volker Grimm, Uta Berger, Stefano Mammola Have you ever lost hours navigating supplementary materials—clicking between the main text and dozens of auxiliary files only to encounter broken links, illegible figures, and undefined variables and acronyms? If so, you’re not alone. What should support scientific communication has instead become an obstacle: supplementary information (SI) increasingly suffers from inconsistent formatting, poor accessibility, and fragmented organization that impedes rather than advances understanding. This is disheartening since the SI, if used effectively, has the power to enhance transparency, credibility, and reproducibility of research. Therefore, we propose 10 simple rules to help authors design SI that genuinely increase the impact of their research. The rules emphasize treating SI with the same care as the main text, using it strategically to support the scientific narrative while preserving clarity and focus. Key recommendations include creating a single, well-structured, self-contained SI master document; ensuring explicit cross-referencing between the main text and SI; making SI machine-readable; and avoiding the misuse of SI as a substitute for proper data repositories. We also highlight the importance of creativity in choosing appropriate formats and strict adherence to journal-specific guidelines. Finally, when available, we advocate the use of standardized templates to improve consistency, readability, and reuse across studies. By following these rules, authors can substantially increase the scientific impact of their work while at the same time contributing to more sustainable research practices.

19.
arXiv (CS.AI) 2026-06-16

Phase-Aware Guidance Injection for Recurrent MAPPO in Assembly-Line Disruption Recovery

arXiv:2606.16330v1 Announce Type: new Abstract: Disruption recovery in industrial assembly lines requires timely decisions under machine faults, worker absence, and emergency orders. Existing methods either rely on rigid handcrafted recovery logic or learn adaptive policies that do not readily exploit heterogeneous external recovery knowledge at decision time to reduce abnormal recovery time (ART) and preserve on-time delivery (OTD). To address this gap, we propose a phase-aware guidance injection framework that augments a trained recurrent MAPPO (RMAPPO) scheduling policy through logit-level action bias during evaluation. The framework provides a unified decision-time interface for rule-based, replay-based, and online LLM-based guidance, while activating intervention only during abnormal and recovery phases. Experiments on a custom AssemblyLineEnv show that high-quality rule guidance yields the strongest gains, replay-based guidance degrades smoothly under imperfect availability, and online LLM guidance still provides useful intermediate improvements. These results show that decision-time guidance injection can exploit heterogeneous recovery hints without redesigning the actor.

20.
medRxiv (Medicine) 2026-06-18

From Paper Letters to an Integrated Digital Workflow: Improving Efficiency, Reliability, and Engagement in Health Guidance

Background: Post-checkup health guidance in Japan has traditionally relied on paper-based communication and manual administrative processes. These workflows are time-consuming, prone to transcription errors, and can delay timely engagement with health guidance recipients. Objective: To assess whether replacing a paper-based workflow with an integrated digital system using Microsoft Access, robotic process automation (RPA), and web-based responses could improve administrative efficiency, operational reliability, and engagement among health guidance recipients. Methods: This single-site quality improvement initiative redesigned the existing letter-based workflow. Access served as a central interface for managing recipients and generating guidance letters. RPA (EzRobot) automated repetitive clerical and billing-related tasks. A web form accessed via a QR code enabled recipients to respond digitally. Outcomes included manual administrative handling time per case, occurrence of transcription-related errors, health guidance completion rate, and guidance duration distribution. Results: Following implementation, staff active handling time per case decreased from approximately 10 minutes to less than 1 minute (approximately 30 seconds), while automated RPA execution typically required about 4-5 minutes per case without staff input. No transcription-related errors were detected during the post-implementation observation period. Health guidance completion rates improved from 28.3% to 39.2% (chi-square test, P=200 days decreased from 30.5% to 20.9% and cases with >=240 days decreased from 13.6% to 8.9% (R4 n=59, R5 n=158). Conclusion: An integrated Access-RPA-Web workflow was associated with improvements in administrative efficiency and operational reliability in post-checkup health guidance while retaining human verification and exception handling. This pragmatic, non-AI-dependent approach may offer a useful model for process-level improvement in preventive care settings.

21.
medRxiv (Medicine) 2026-06-17

Cost-effectiveness of measles rapid diagnostic tests for replacing or expanding laboratory testing in Ethiopia

Background: In low- and middle-income countries, laboratory testing to rapidly detect measles outbreaks is limited by infrastructure availability and high costs. This study estimates the potential impact and cost-effectiveness of measles rapid diagnostic tests (RDTs) if implemented nationally in Ethiopia to either replace or expand current testing. Methods: An agent-based model to simulate measles outbreaks was calibrated to Ethiopian measles surveillance data. Modelled outbreak outcomes were aggregated over a 10-year period. Scenarios included using RDTs to (1) replace laboratory testing; (2) replace epidemiological linkage; and (3) increase case detection, in addition to replacing laboratory testing and epidemiological linkage. Testing and outbreak response costs (in 2025 US$) were obtained from Ethiopian Public Health Institute from a government perspective. Total costs and disability-adjusted life years (DALYs) for each scenario were compared to baseline. Results: All scenarios were cost saving compared to baseline. Replacing laboratory testing with RDTs saved US$4.2M (3.2M-4.9M) over 10-years, but due to very low testing rates the benefits of eliminating laboratory testing delays were offset by missed cases from the lower RDT sensitivity, leading to similar outbreak detection times and DALYs. Replacing epidemiological linkage with RDTs had similar DALYs but increased the cost savings to US$9.7M. Using RDTs to double case detection reduced outbreak detection time from 113 to 80 days, averted 17,000 DALYs, and saved US$4.3M. Conclusions: In Ethiopia, use of measles RDTs could be cost saving, and if used to expand testing could prevent measles infections through faster outbreak detection and response.

22.
medRxiv (Medicine) 2026-06-18

A Brain-Aging Transcriptomic Signature Reclassifies WHO Glioma Grade and Predicts Survival Independently of IDH Status: A Multi-Cohort Study

Background Despite WHO grade and IDH status, significant survival differences remain in diffuse gliomas. We hypothesized that a brain-aging transcriptomic signature, reflecting neuroinflammation, myeloid infiltration, and synaptic loss, would independently predict survival and allow for molecular reclassification. Methods A neurodegeneration score was derived via PCA of brain MRI volumes from 1,057 OASIS-3 subjects and projected onto 888 TCGA-LGG/GBM (discovery) and 693 CGGA gliomas (validation). A 14-gene signature of glial/myeloid (GFAP, AQP4, TYROBP, TREM2, C1QA, CD68, ITGAM) and neuronal (SYP, DLG4, GRIN1, GRIA1, SNAP25, SYN1, RBFOX3) genes were computed. Elastic-net Cox regression identified a 3-gene panel (C1QA, CD68, GRIA1). Kaplan-Meier, multivariate Cox, decision curve, and single-cell RNA-seq analyses were performed. Results High brain-aging scores predicted poorer overall survival (p < 0.0001) and remained an independent prognostic factor after adjusting for WHO grade and IDH status (z = 4.72, p < 0.001); chronological age was non-significant (p = 0.231). In IDH-mutant gliomas, significance was confirmed in both cohorts (TCGA p = 0.027; CGGA p < 0.0001). Bidirectional reclassification showed high-risk Grade 2 tumors with Grade 3-like survival (p = 0.00089), and indolent Grade 3 tumors resembling Grade 2 by Ki-67. Single-cell RNA-seq confirmed macrophage localization of signature genes; DCA demonstrated net benefit over grade alone at 5-30% probability thresholds. Conclusions A brain-aging transcriptomic signature independently predicts glioma survival beyond WHO grade and IDH status, validated in an independent Chinese cohort, with clinical utility for identifying high-risk Grade 2 and sparing over-treatment of indolent Grade 3 tumors.

23.
bioRxiv (Bioinfo) 2026-06-22

PanRes: A database of latent and acquired antimicrobial resistance allowing 3D-based protein homology search

Antimicrobial resistance databases are central to genomic surveillance, but resistance determinants remain distributed across resources with different scopes, structures, and annotations. We developed PanRes, a curated resistance database of 11,717 genes integrating acquired and latent determinants of antibiotic, biocide, and metal resistance within a unified ontology. We predicted representative protein structures and clustered them by structural similarity, grouping proteins into 598 structurally conserved clusters coherent despite sequence divergence. Their structure-guided alignments were used to build Hidden Markov Models (HMMs) for remote homology search. In wastewater metagenomes from seven European cities, PanRes 3D-based HMMs expanded detection beyond high-confidence BLAST, with 35.2% of retained hits identified only by the HMMs and generally showing greater divergence from known proteins. For beta-lactamases, several proteins retained beta-lactamase-like folds and catalytic geometry despite weak sequence similarity. PanRes is available through an interactive web platform (https://panres.rambio.dk/), a structure-informed resource for exploring the whole resistome.

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

Evaluating LLM Personalization via Semantic Constraint Verification

Current evaluation paradigms for Large Language Model (LLM) personalization rely heavily on brittle surface-matching metrics or computationally expensive LLM-as-a-judge protocols, both of which lack interpretability. To address these limitations, we introduce Natural Language Inference Constraint Verification (NLICV), a scalable, semantically invariant framework that maps sentence meanings to truth-condition sets to verify personalization constraints via a Natural Language Inference (NLI) model. Moving beyond binary scoring, NLICV categorizes LLM behaviors into four distinct modes: personalization, generalization, sycophancy, and failure. Extensive experiments demonstrate that NLICV aligns closely with human annotations while drastically reducing the latency and token costs associated with LLM judges (up to 2100 inference speedup). Finally, through an ablation-based procedure, NLICV pinpoints the exact sentences driving the constraint verification, yielding faithful, understandable evidence for its evaluations.

25.
arXiv (CS.AI) 2026-06-11

Reinforcement Learning Disrupts Gradient-Based Adversarial Optimization

arXiv:2606.12251v1 Announce Type: cross Abstract: Gradient-based adversarial attacks remain a dominant threat to deep neural networks (DNNs), as they exploit gradient information to efficiently optimize adversarial perturbations. To address this, we investigate whether reinforcement learning (RL) training can disrupt the gradient structure used by attackers by training image classifiers with policy-gradient objectives and epsilon-greedy exploration. Through systematic experiments across CIFAR-10, CIFAR-100, and ImageNet-100 with multiple architectures, we find that RL-trained classifiers significantly disrupt gradient-based adversarial optimization. To explain this, we conduct a comprehensive mechanism analysis using loss landscape visualization, static and dynamic gradient indicators, and predictive entropy. Our analysis reveals that RL acts as an implicit regularizer, producing models with highly unstable gradient directions and smaller gradient magnitudes. This combination makes each PGD step both unreliable in direction and limited in magnitude, causing gradient-based attacks to fail within practical iteration budgets. We further show that combining RL with adversarial training (RL-adv) provides a dual-layer defense operating at two complementary levels: RL degrades gradient information available to attackers (gradient-level defense), while adversarial training strengthens decision boundaries (boundary-level defense). RL-adv achieves the highest robustness across all major attack types evaluated, including gradient-based (PGD, AutoAttack), transfer-based, and query-based attacks, outperforming SL-adv by a significant margin. These findings identify RL-induced gradient disruption as a complementary robustness mechanism and motivate future research on hybrid SL-RL training schedules that combine SL's efficiency with RL's gradient-regularization properties.