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01.
arXiv (CS.LG) 2026-06-19

On the Oracle Complexity of Interpolation-Based Gradient Descent

Authors:
Dongmin Lee↗William Lu↗Anuran Makur↗

arXiv:2606.19878v1 Announce Type: new Abstract: Recent work on first-order optimizers for empirical risk minimization (ERM) has suggested that smoothness of ERM loss functions in the training data, rather than in the optimization parameters, can be leveraged to improve the oracle complexity of gradient descent (GD) methods. In this paper, we propose an inexact gradient method, piecewise polynomial interpolation-based gradient descent (PPI-GD), which approximates the full gradient in each iteration by querying the first-order oracle at equidistant points in the data domain to construct polynomial interpolants of the resulting gradient samples over appropriately sized patches of the data domain. We analyze the oracle complexity of PPI-GD for strongly convex and non-convex loss functions when the data space dimension is bounded by a polylogarithmic function of the number of training samples, and find it to outperform several GD variants in key regimes when the loss function is sufficiently smooth. Furthermore, our analysis extends several techniques from the error analysis of bicubic spline interpolants to the setting of $d$-variate tensor product polynomial interpolants which may be of independent interest in interpolation analysis.

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02.
bioRxiv (Bioinfo) 2026-06-18

Metrics for Evaluating Biological AI Model Predictive Accuracy at the Data-Substrate Level

Authors:
Ewing↗M. A↗

Reports in the biological literature disagree on whether a given model can predict a biological outcome from a given data sample — one study finding a model capable, another, on the same kind of data, finding it is not. This is particularly a challenge in relation to LLMs–where the models are large and opaque, with weights and training data inaccessible.textbf{ }Such disagreements cannot be settled by directly inspecting the model. To address this challenge, we considertextbf{ }an alternative approach: assessing whether the data sample is adequate to support the prediction asserted. For a given dataset, its substrate — the underlying structure of the data — determines what any model can recover, independent of architecture or capacity. At the same time, predicting the present state of a biological process and predicting the direction of its future change are different tasks; the second is supportable among AI models only where the data encode direction as determinable from the state — a property we call encoding — and is unsupportable where the same observed state precedes change in opposite directions — a property we call non-identifiability, in the informational rather than the statistical sense. We introduce two generic metrics, Predictive Blindness Risk (PBR) and Prediction Indeterminacy Measure (PIM), that evaluate a data substrate for predictive accuracy directly — without access to model weights, architecture, or training data — and locate the regions of a data substrate where a predictive claim can be supported and where it cannot. Using human biological subjects, we employ the Yale Brain Metastases Longitudinal Data (1,430 human subjects; 11,892 MRI studies; four sequences) and show that direction of change was non-identifiable across regions encompassing the majority of transitions; a nonlinear AI model gained essentially nothing over majority-direction prediction there while recovering direction near-perfectly where the state encoded it; and model accuracy tracked data-substrate resolvability continuously (Spearman {rho} = -0.95 to -1.00). The metrics adjudicate, before any model is trusted and from the data alone, where claims of predictive accuracy — of state, or of the law of change — can be supported.

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

Improved Knowledge Distillation for Land-Use Image Classification

Authors:
Arundhuti Sur↗Abhiroop Chatterjee↗Susmita Ghosh↗Emmett Ientilucci↗

In the present article, an improved Knowledge Distillation (KD) framework has been proposed for efficient compression of deep convolutional neural networks for land-use image classification task. Motivated by the need to achieve competitive classification accuracy while reducing computational complexity, a teacher-student learning paradigm is adopted in which a VGG16 network transfers knowledge to a lightweight MobileNetV2 model. The proposed framework integrates hard supervision from ground truth labels with a soft supervision strategy that combines Kullback-Leibler divergence and Cosine Similarity losses. Experiments conducted on three land-use datasets show that the proposed KD-based method yields improved performance, and achieves an accuracy of 99.04%, outperforming both baseline student training and single-loss distillation approaches, while retaining substantial model compression.

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04.
arXiv (CS.CL) 2026-06-19

MedRLM: Recursive Multimodal Health Intelligence for Long-Context Clinical Reasoning, Sensor-Guided Screening, Evidence-Grounded Decision Support, and Community-to-Tertiary Referral Optimization

Authors:
Aueaphum Aueawatthanaphisut↗

Real-world clinical decision support requires reasoning over heterogeneous and longitudinal patient information rather than answering isolated medical questions. However, current medical large language models and retrieval-augmented generation systems often rely on single-step prompting or retrieval, which can be fragile when clinical evidence is distributed across long electronic health records, medical images, sensor streams, guidelines, and referral constraints. This paper proposes MedRLM, a Recursive Multimodal Health Intelligence framework for long-context clinical reasoning, sensor-guided screening, and community-to-tertiary referral support. Instead of compressing all patient information into one prompt, MedRLM treats the patient case as an external clinical environment that can be recursively inspected, decomposed, retrieved, verified, and synthesized. The framework coordinates specialized agents for clinical text, longitudinal EHR, medical imaging, physiological sensor signals, guideline retrieval, uncertainty auditing, and referral planning. It further introduces a Clinical Evidence Graph Memory to connect patient-specific observations with retrieved evidence, standardized definitions, sensor-derived biomarkers, and referral criteria. A sensor-guided recursive triggering mechanism activates deeper reasoning when abnormal physiological or behavioral patterns are detected, while uncertainty-gated refinement supports clinician review for high-risk or low-confidence cases. We also outline a real-data evaluation design using public and credentialed clinical datasets spanning EHR, radiology, ECG, ICU time series, and referral-proxy outcomes. MedRLM aims to move medical AI from static question answering toward auditable, multimodal, and workflow-aware clinical decision support.

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05.
arXiv (CS.CV) 2026-06-12

Dual-Domain Equivariant Generative Adversarial Network for Multimodal CT-PET Synthesis

Authors:
Gabriel Steele↗Alzahra Altalib↗Alessandro Perelli↗

We present a Dual-Domain Equivariant Generative Adversarial Network (DDE-GAN) for multimodal CT-PET image synthesis. Traditional GAN-based approaches often operate solely in the spatial domain and ignore geometric consistency, resulting in limited structural fidelity. DDE-GAN addresses these challenges by jointly learning from both spatial and frequency (Fourier) domains, capturing complementary anatomical and spectral information. Furthermore, rotational equivariance embedded in the physics of the CT and PET measurements are integrated into the loss of both the generator and discriminator to ensure consistent responses under rotations, improving anatomical accuracy. A hierarchical dual-domain training strategy enforces intra- and inter-domain consistency through multi-stage loss functions. Evaluated on the HECKTOR 2022 CT-PET dataset, DDE-GAN achieves superior synthesis quality over baseline models for CT-PET image synthesis. The results demonstrate that combining dual-domain learning with geometric equivariance substantially enhances multimodal image synthesis accuracy and robustness, enabling practical applications in PET completion and data augmentation.

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

Compute Efficiency and Serial Runtime Tradeoffs for Stochastic Momentum Methods

Authors:
Depen Morwani↗Alexandru Meterez↗Pranav Nair↗Sham Kakade↗

arXiv:2606.19179v1 Announce Type: cross Abstract: Stochastic momentum methods such as heavy ball (HB), Nesterov momentum, and variants of Accelerated SGD (ASGD) [Kidambi et al., 2018] are widely used in modern training, but their stochastic benefits depend on two distinct quantities: serial runtime, the number of iterations needed to reach a target accuracy, and compute efficiency (CE), the inverse total gradient-query or FLOP cost. Larger batches reduce serial runtime without hurting CE only when the contraction gap grows linearly with batch size. We study stochastic HB and ASGD for consistent linear regression with Gaussian covariates and prove finite-dimensional, discrete-time lower bounds on their batch-size tradeoffs. Our first result shows that HB does not improve the CE frontier over SGD for arbitrary spectra; rather, it preserves SGD-level CE over a larger batch-size window, allowing larger batches to reduce serial runtime until HB reaches its deterministic accelerated scale. This window can be a factor $\sqrt{\kappa}$ larger than the SGD critical batch size. For ASGD, the picture is more spectrum-dependent: for rapidly decaying power-law spectra, ASGD improves small-batch CE over HB/SGD, but as batch size grows it trades this CE advantage for improved serial runtime. Synthetic linear-regression experiments verify these qualitative regimes, including near-overlap of ASGD and HB for slowly decaying spectra and the predicted CE–serial tradeoff for rapidly decaying spectra.

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07.
arXiv (CS.CL) 2026-06-11

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

Authors:
Meherun Farzana↗Aniket Joarder↗Mahmudul Hasan↗Md. Mosaddek Khan↗

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.

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09.
medRxiv (Medicine) 2026-06-15

Primary care practitioners preconception health literacy and information-seeking: A cross-sectional survey.

Authors:
Caut↗Schoenaker↗McIntyre↗Steel↗

Background Parental health before pregnancy influences maternal and child outcomes. Primary care professionals, including general practitioners [GPs], midwives, and naturopaths, can provide preconception care, yet many report limited knowledge and difficulty accessing relevant information. This study described Australian GPs, midwives, and naturopaths preconception health literacy, including knowledge and ability to access information. Methods Between July and September 2022, Australian GPs, midwives, and naturopaths completed a 32-item online cross-sectional survey. Participants were recruited through professional associations, and data were analysed using descriptive and inferential statistics Results Participants (N=373) included naturopaths (40.7%), GPs (32.4%), and midwives (26.8%). Reported barriers to clinician health literacy including lack of preconception care resources (25.5%), and limited clinician knowledge (23.6%). The proportion identifying limited clinician knowledge differed significantly between professions (GP: 31.4%; midwives: 23.0%; naturopaths: 17.8%; p=0.030). The highest level of accurate knowledge regarding preconception exposures was for pre-pregnancy obesity (82.7%), while low birth weight was the most accurately identified preconception outcomes (83.7%). Incorrect responses were most common for maternal multivitamin use as an exposure (28.3%) and childhood leukaemia as an outcome (26.3%). Differences between professions were strongest for infant outcomes, with moderate associations observed for shoulder dystocia (V=.2355), precipitous labour (V=.2173), macrosomia (V=.2060), labour dystocia (V=.2018) and cryptorchidism (V=.2018). Discussion Preconception health literacy varies across primary care professions. Clinicians require greater access to targeted resources and education tailored to their differing scopes of practice and experience. Improving clinician preconception health literacy may strengthen consistent evidence-based care and support better maternal, child, and long-term family health outcomes.

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10.
arXiv (quant-ph) 2026-06-11

Sharing quantum indistinguishability with multiple parties

Authors:
Lemieux Wang↗Hanwool Lee↗Joonwoo Bae↗Kieran Flatt↗

arXiv:2512.15199v3 Announce Type: replace Abstract: Quantum indistinguishability of non-orthogonal quantum states is a valuable resource in quantum information applications such as cryptography and randomness generation. In this article, we present a sequential state-discrimination scheme that enables multiple parties to share quantum uncertainty, in terms of the max relative entropy, generated by a single party. Our scheme is based upon maximum-confidence measurements and takes advantages of weak measurements to allow a number of parties to perform state discrimination on a single quantum system. We review known sequential state discrimination and show how our scheme would work through a number of examples where ensembles may or may not contain symmetries. Our results will have a role to play in understanding the ultimate limits of sequential information extraction and guide the development of quantum resource sharing in sequential settings.

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

Controlled Dynamics Attractor Transformer

Authors:
Cheng Zhang↗Minnan Luo↗Zesheng Yang↗Ming Li↗Yong-Jin Liu↗Qinghua Zheng↗

arXiv:2606.15207v1 Announce Type: cross Abstract: Transformer architectures have dramatically advanced representation learning and inference in deep models through self-attention mechanisms. In parallel,associative memory (AM) frameworks map representations onto energy landscapes, offering interpretable retrieval mechanisms. However, their continuous-time inference dynamics lack the biological plausibility of classical Continuous Attractor Neural Networks (CANNs). To bridge this gap, we propose Controlled Dynamics Attractor Transformer (CDAT), which couples a mixture von Mises-Fisher (Mo-vMF) attention energy with a Hopfield refinement energy, while augmenting energy descent with a CANN-inspired excitation-inhibition modulation. CDAT instantiates a topology-constrained dynamical system whose couplings encode relational structure among tokens, thereby linking attractor-style dynamics to modern energy-based attention. We further provide a constructive dissipation analysis to formally establish their controlled inference dynamics. Benefiting from these robust and structured dynamics, CDAT achieves state-of-the-art performance across multiple benchmarks in graph anomaly detection and graph classification.

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12.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

Authors:
Eger↗S. J↗Lopez↗Gomez Navarro↗L. F↗Pena-Tauber↗Cochran↗J. N↗Hiatt↗S. M↗Gelvez↗Garcia-Garcia↗…

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

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13.
arXiv (CS.CV) 2026-06-17

Recover Semantics First, Generate Better: Improved Latent Modeling for 3D MRI Reconstruction and Cross-Contrast Synthesis

Authors:
Yonghao Chen↗Sicheng Yang↗Rui Tang↗Lei Zhu↗

Multi-contrast magnetic resonance imaging (MRI) provides complementary information for clinical diagnosis. However, acquiring all MRI sequences is often time-consuming and costly. Recent generative models perform cross-contrast synthesis to address this issue by inferring absent contrasts from the available ones. Nevertheless, synthesizing 3D MRI presents significant challenges. Due to the massive volume sizes, operating directly in the pixel space is computationally prohibitive; therefore, a common approach is to first compress the 3D volumes into a latent space and subsequently train generative models in that space. We observe that existing compression architectures face several critical issues: they under-preserve long-range anatomical coherence, discard clinically meaningful semantics, and rely on optimization objectives that lead to over-smoothed reconstructions. Ultimately, these shortcomings compromise the performance of subsequent generative models. In this work, we propose a semantics-first latent modeling framework for 3D MRI reconstruction and cross-contrast synthesis. Specifically, we introduce a Latent Harmonization Encoder (LHE) to capture global anatomical dependencies, ensuring coherent volumetric representations. To mitigate semantic degradation during latent compression, we further design a Semantic Recovery Block (SRB) that injects high-level priors from a self-supervised semantic teacher, enhancing contrast-aware separability in the latent space. Additionally, we propose an Anatomy-aware Frequency Loss (AFL) to adaptively preserve diagnostically relevant high-frequency structures. Extensive experiments on two public multi-contrast MRI datasets demonstrate consistent improvements in reconstruction fidelity and cross-contrast synthesis quality. Our code is available at https://github.com/script-Yang/RSF.

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

MASK: Multi-Agent Semantic K-Scheduling for Risk-Sensitive 6G Robotics

Authors:
Ahmet Gunhan Aydin↗Elif Tugce Ceran↗

arXiv:2606.11249v1 Announce Type: cross Abstract: Realizing the vision of 6G connected robotics requires reconciling high-performance collaborative control with the rigid spectral limitations of physical wireless channels. In realistic collaborative sensing scenarios, spectral resources are quantized into finite physical resource blocks or orthogonal subcarriers, rendering simultaneous transmission by all agents infeasible. To address this, we propose Multi-Agent Semantic K-Scheduling (MASK), a control architecture designed to sustain robust, risk-aware coordination under strict instantaneous bandwidth caps. We introduce Arbiter-Assisted Semantic Information Gating (A-SIG), a lightweight coordination mechanism that enforces hard access constraints by scheduling only the top-K agents based on locally computed semantic importance scores. By aggregating these prioritized observations into a compact latent state, a self-supervised global encoder enables a distributional policy to mitigate tail risks despite data sparsity. We evaluate MASK across diverse benchmarks, demonstrating that it matches the performance of communication-unconstrained baselines even when channel access is restricted to a small fraction of the swarm size. Furthermore, the framework exhibits inherent resilience to packet erasures, validating semantic scheduling as a critical enabler for resource-constrained 6G systems.

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15.
arXiv (CS.LG) 2026-06-17

Conformalized Quantum DeepONet Ensembles for Scalable Operator Learning with Distribution-Free Uncertainty

Authors:
Purav Matlia↗Christian Moya↗Guang Lin↗

arXiv:2605.00330v2 Announce Type: replace Abstract: Operator learning enables fast surrogate modeling of high-dimensional dynamical systems, but existing approaches face two fundamental limitations: quadratic inference complexity and unreliable uncertainty quantification in safety-critical settings. We propose Conformalized Quantum DeepONet Ensembles, a framework that addresses both challenges simultaneously. By leveraging Quantum Orthogonal Neural Networks (QOrthoNNs), we reduce operator inference complexity from O(n^2) to O(n), enabling scalable evaluation over fine discretizations. To provide rigorous uncertainty quantification, we combine ensemble-based epistemic modeling with adaptive conformal prediction, yielding distribution-free coverage guarantees. A key challenge in ensembling is that naive parallelism scales hardware resources linearly with the number of models. We resolve this by using Superposed Parameterized Quantum Circuits (SPQCs), which compress multiple ensemble members into a single circuit and enable simultaneous multi-model execution. Experiments on synthetic partial differential equations and real-world power system dynamics demonstrate that our approach achieves accurate predictions while maintaining calibrated uncertainty under realistic quantum noise. These results establish a practical pathway toward scalable, uncertainty-aware operator learning in quantum machine learning.

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16.
arXiv (CS.CL) 2026-06-12

Direct Preference Optimization for Chatbot Fine-Tuning: An Empirical Study

Authors:
Yvonne Qiu↗Dezhi Yu↗ShuoJia Fu↗

We present an approach to fine-tuning large language models using Direct Preference Optimization (DPO), a reinforcement learning technique. Our experimental results demonstrate that DPO simplifies the training pipeline, improves computational efficiency, and achieves competitive performance. The evaluation using BLEU, ROUGE, and cosine similarity metrics indicates effective learning and convergence, though further investigation is needed to address observed training instability.

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

Getting Better at Working With You: Compiling User Corrections into Runtime Enforcement for Coding Agents

Authors:
Yujun Zhou↗Kehan Guo↗Haomin Zhuang↗Xiangqi Wang↗Yue Huang↗Zhenwen Liang↗Pin-Yu Chen↗Tian Gao↗Nuno Moniz↗Nitesh V. Chawla↗Xiangliang Zhang↗

Interactive LLM agents are becoming part of daily work, but they do not reliably become easier to work with over time: a correction remembered in one session may still be violated in the next. We study this gap between preference access and preference compliance. In tasks derived from anonymized real-user friction cases, Mem0 memory still leaves 57.5% of applicable preference checks violated. We introduce Test-time Rule Acquisition and Compiled Enforcement (TRACE), a drop-in skill-layer pipeline for coding-agent runtimes that mines user corrections, rewrites them as atomic rules, and compiles them into runtime checks that must pass before an agent completes future tasks. Unlike runtime checks written ahead of time by developers, TRACE skills come from the user's own chat corrections. We evaluate TRACE with simulated user-in-the-loop experiments on ClawArena coding-agent tasks and MemoryArena-derived memory-intensive tasks. On ClawArena, TRACE reduces held-out preference violation from 100.0% to 37.6% on in-distribution tasks and from 100.0% to 2.0% on out-of-distribution tasks. On MemoryArena-derived tasks, TRACE reduces in-distribution violation from 100.0% to 60.5% while matching or exceeding the strongest memory baseline on task pass. These results suggest that compiling corrections into runtime enforcement can address a repeated-friction failure mode that memory alone does not reliably solve, reducing the need for users to restate the same correction across future sessions. Experiment code is available at https://github.com/YujunZhou/TRACE_exp, and the deployable skill is available at https://github.com/YujunZhou/tellonce.

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

When Cars Have Stereotypes: Auditing Demographic Bias in Objects from Text-to-Image Models

Authors:
Dasol Choi↗Jihwan Lee↗Minjae Lee↗Minsuk Kahng↗

While prior research on text-to-image generation has predominantly focused on biases in human depictions, demographic bias in generated objects remains relatively underexplored. We introduce SODA (Stereotyped Object Diagnostic Audit), a novel framework for systematically measuring these biases through automated attribute discovery and three standardized metrics: Base vs. Demographic Divergence (BDS), Cross-Demographic Disparity (CDS), and Visual Attribute Concentration (VAC). Applying SODA to 8,000 images across five state-of-the-art models and eight object categories (e.g., cars), we find that "neutral" prompts produce outputs most visually similar to middle-aged and White people, suggesting these groups are implicitly over-represented in model defaults. Furthermore, demographic cues trigger highly skewed stereotypical outputs: 26.6% of object-model-demographic combinations produce results where all 20 generated images share the exact same attribute value (e.g., rose gold laptops for women). Finally, prompt-level debiasing reduces inter-group disparity but paradoxically collapses within-group diversity, replacing one stereotype with another. SODA offers a practical pipeline for making these implicit associations measurable, serving as a step toward more responsible AI development.

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19.
medRxiv (Medicine) 2026-06-22

A Plasmodium vivax controlled human infection and transmission model to evaluate interventions across the life cycle

Authors:
Geraedts↗T. J. M↗Bok↗Graumans↗Gemert↗G.-J. v↗Lorenz↗F.-R↗Gmeiner↗Stoter↗Teelen↗Lanke↗…

Background Plasmodium vivax is an underappreciated cause of malaria disease burden. No reproducible and standardized full life-cycle controlled human malaria infection (CHMI) model to accelerate development of novel interventions is available. Methods This transmission-CHMI trial was conducted in Nijmegen, Netherlands. Healthy, malaria-naive adults were sequentially enrolled into three cohorts of four and inoculated with the asexual blood-stage isolate PvW1. Primary endpoint was proportion of oocyst-positive laboratory-reared Anopheles stephensi mosquitoes. The sequential design allowed for adaptations between cohorts. At parasitemia >10 parasites/microL or symptom onset, participants received oral gametocyte-sparing treatment (GST): mepacrine (Cohort 1 and 3; 100 mg at 0, 8 16 hours, then once daily for 3 days) or piperaquine (Cohort 3; 480 mg single-dose). Transmission was assessed by direct skin feeding (DSF) and membrane feeding assay (DMFA) with and without enrichment of gametocytes. End-of-study treatment was atovaquone-proguanil (1000/400 mg once daily for 3 days). The trial was registered: NL-OMON57011. Findings Participants were enrolled between September 17, 2024 and March 25, 2025, all (12/12) developed parasitemia and transmitted PvW1 to mosquitoes. No serious adverse events occurred. Most adverse reactions were related to malaria. Mepacrine and piperaquine reduced asexual parasitemia while preserving gametocytemia and transmission. Peak transmission occurred within 3 days after GST and depended on the parasite developmental cycle, with highest gametocyte-infectivity ~48 h post ring-stage. In Cohort 3, mosquito infection reached 100% in all transmission assays. Median peak oocyst counts were 24 (IQR: 14-31) for DSF, 17 (12-19) for DMFA, and 150 (116-199) for enriched DMFA. A two-fold increase in pre-GST maximal parasitemia was associated with 20 additional oocysts (95% CI 8,6-32) in enriched DMFA. Sporozoites were viable in primary human hepatocytes. Interpretation A PvW1 transmission-CHMI is reproducible and safe, enabling P. vivax sporozoite production, relapse models and evaluation of transmission-blocking interventions.

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20.
bioRxiv (Bioinfo) 2026-06-16

RetroMol: Parsing a shared encoding from natural products and their biosynthetic gene clusters

Authors:
Meijer↗Williams↗S. E↗Terlouw↗Charusanti↗Kok↗Skinnider↗M. A↗Weber↗van der Hooft↗J. J. J↗Healy↗…

Natural products such as polyketides and nonribosomal peptides (NRPs) are important sources of bioactive compounds, including many antibiotics. Many of them are assembled by modular enzyme complexes and further modified and diversified by tailoring reactions encoded by biosynthetic gene clusters (BGCs). Although natural products and their coding BGCs describe different data modalities of the same biochemical process, a unified language to jointly describe their biochemistry is lacking. Here we introduce a sequence-based representation of the core biosynthesis of modular natural products, which we call primary sequences, that bridges chemical structures and BGCs. We also present RetroMol, an algorithm that parses either natural product structures or their encoding BGCs into their primary sequences of natural product building blocks. RetroMol allows for similarity scoring between natural products and BGCs, enabling the retrieval of compounds, BGCs, and a combination of the two, based on their biosynthetic similarity. This can, for instance, be used to retrieve biosynthetically similar but structurally dissimilar compounds, or link natural products to candidate coding BGCs in large experimental datasets. We demonstrate the latter by rediscovering the nocardichelin B BGC as a proof of principle. We also exemplify the utility of biosynthetic similarity by showing various pairs of biosynthetically similar compounds with low structural similarity. Together, these results establish primary sequences as a shared biosynthetic encoding for natural product comparison and BGC prioritization.

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21.
arXiv (CS.CV) 2026-06-12

TimeLens: On-Device Artifact Recognition with Retrieval-Augmented Question Answering for the Grand Egyptian Museum

Authors:
Rawan Hesham↗Ali Ashraf↗Amr Ahmed↗Malak Alaa↗Omar Ahmed↗Omar Wagih↗

TimeLens is an AI-powered bilingual mobile guide for the Grand Egyptian Museum (GEM). Pointing a phone at an exhibit, a visitor sees the artifact recognized in real time and can ask follow-up questions answered in English or Arabic. The work addresses three problems specific to in-gallery deployment: fine-grained visual similarity among 51 catalogued artifacts (many near-identical Ramesside statues), the gap between curated training data and handheld camera conditions, and the risk of an AI guide stating unsupported historical facts. Two engineering contributions are reported. First, an on-device artifact detector was developed through a data-quality-driven iteration study – from foundation-model auto-annotation (YOLO-World), through spatial label-cleaning rules, to a fully hand-annotated dataset – isolating label quality as the decisive factor: the final YOLOv8n model resolves every previously failing class while remaining a 5.97 MB TensorFlow Lite asset that runs in real time on a mid-range phone (mAP@0.5 = 0.995, mAP@0.5:0.95 = 0.924). Second, a bilingual Retrieval-Augmented Generation (RAG) guide, grounded in a 108-record ChromaDB knowledge base, was benchmarked across seven candidate language models, with Gemma 4 E2B (Q4 K M) selected; ten targeted optimizations reduce end-to-end latency from over 30 s to approximately 10 s. Both subsystems are integrated in a production Flutter application with bilingual interface, museum location gating, and text-to-speech support.

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22.
arXiv (CS.CL) 2026-06-11

SoftMatcha 2: A Fast and Soft Pattern Matcher for Trillion-Scale Corpora

Authors:
Masataka Yoneda↗Yusuke Matsushita↗Go Kamoda↗Kohei Suenaga↗Takuya Akiba↗Masaki Waga↗Sho Yokoi↗

We present SoftMatcha 2, an ultra-fast and flexible search algorithm that enables search over trillion-scale natural language corpora in under 0.3 seconds while allowing semantic variations in the form of substitution, insertion, and deletion. Our approach employs string matching based on suffix arrays that scales well with corpus size, and represents words as vectors, which underpin its semantic flexibility. To mitigate the combinatorial explosion induced by the semantic relaxation of queries, our method is built on two key algorithmic ideas: dynamic corpus-aware pruning and fast exact lookup enabled by a disk-aware design. We theoretically analyze the efficiency of the proposed method, indicating that it can mitigate exponential growth in the search space. Empirically, on FineWeb-Edu (Lozhkov et al., 2024) (1.4T tokens), it attains substantially lower search latency than existing methods: infini-gram (Liu et al., 2024), infini-gram mini (Xu et al., 2025), and SoftMatcha (Deguchi et al., 2025). As a practical application, our method uncovers benchmark contamination in training corpora that existing approaches miss, and it also benefits information retrieval and paraphrase detection. We also provide an online demo of fast, soft search across corpora in seven languages.

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23.
medRxiv (Medicine) 2026-06-18

Intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis for acute medium vessel occlusion (MeVO-TNK): Study rationale and design

Authors:
Deng↗Liu↗C.-C↗Wang↗Y.-H↗Ao↗D.-H↗Huang↗Xie↗Zhang↗Kong↗Q.-Q↗…

Background The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra-arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand-alone IAT remains undefined. Aim To preliminarily evaluate the efficacy and safety of intra-arterial tenecteplase (IA-TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA-TNK dosing strategy. Design The MeVO-TNK trial is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging-confirmed MeVO will be randomized 1:1 to receive either IA-TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra-arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety. Outcomes The primary efficacy outcome is final infarct volume measured at 72{+/-}24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0-1, 0-2 and 0-3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours. Conclusions This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand-alone IA-TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

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24.
medRxiv (Medicine) 2026-06-12

Immunologically Optimized Zmp1 Peptides Reveal a Translational Serological Biomarker Platform for Tuberculosis Diagnosis Across Disease Manifestations

Authors:
Zade↗O. S↗Yandrapally↗Choudhari↗Gaikwad↗A. V↗Panda↗Neela↗V. S. K↗Devalraju↗K. P↗Eedara↗…

Tuberculosis (TB) diagnosis remains challenging, particularly for extrapulmonary TB (EPTB), where invasive sampling, low bacillary burden, and suboptimal sensitivity of nucleic acid-based tests in peripheral specimens hinder timely detection. Here, we report an immunology-driven strategy for biomarker discovery and development of a peptide-based serological assay targeting Mycobacterium tuberculosis zinc metalloprotease-1 (Zmp1). Leveraging fundamental principles of adaptive immunity that antigenic regions containing overlapping B-cell and CD4 T-helper cell epitopes would preferentially generate high antibody titers through linked recognition and cognate T-cell help, we used an immunoinformatics pipeline to identify two nested immunodominant peptide regions within Zmp1 (Mtb-Zp-NT and Mtb-Zp-CT) enriched for overlapping B- and T-cell epitopes. The diagnostic potential of these peptides was evaluated through ELISA-based serological assays. A blinded pilot study (N=137) demonstrated a clear discrimination between active TB and TB-recovered individuals. The assay was subsequently validated in an expanded cohort (N=875) by screening 6,086 individuals, which identified 457 TB-positive cases. The cohort included pulmonary TB (PTB), EPTB, TB-recovered individuals, household contacts, non-specific infections, and healthy controls. Receiver operating characteristic analyses, supported by DeLong and bootstrap comparisons, revealed superior diagnostic performance of the peptide-based assays relative to full-length Zmp1. Mtb-Zp-CT exhibited the highest accuracy (AUC=0.93; specificity >90%), while Mtb-Zp-NT also demonstrated strong discriminatory power (AUC{approx}0.89). These findings establish that the immunologically optimized Zmp1 peptides are highly promising serological biomarkers for TB and EPTB. More broadly, they demonstrate how mechanistically informed epitope selection can accelerate translation of pathogen-specific immune signatures into sensitive, minimally invasive, and potentially point-of-care diagnostic platforms for resource-limited settings.

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25.
arXiv (CS.AI) 2026-06-18

A CEFR-Inspired Classification Framework with Fuzzy C-Means To Automate Assessment of Programming Skills in Scratch

Authors:
Ricardo Hidalgo-Arag\'on↗Jes\'us M. Gonz\'alez-Barahona↗Gregorio Robles↗

arXiv:2604.00730v2 Announce Type: replace-cross Abstract: Context: Schools, training platforms, and technology firms increasingly need to assess programming proficiency at scale with transparent, reproducible methods that support personalized learning pathways. Objective: This study introduces a pedagogical framework for Scratch project assessment, aligned with the Common European Framework of Reference (CEFR), providing universal competency levels for students and teachers alongside actionable insights for curriculum design. Method: We apply Fuzzy C-Means clustering to 2008246 Scratch projects evaluated via Dr.Scratch, implementing an ordinal criterion to map clusters to CEFR levels (A1-C2), and introducing enhanced classification metrics that identify transitional learners, enable continuous progress tracking, and quantify classification certainty to balance automated feedback with instructor review. Impact: The framework enables diagnosis of systemic curriculum gaps-notably a "B2 bottleneck" where only 13.3% of learners reside due to the cognitive load of integrating Logic Synchronization, and Data Representation–while providing certainty–based triggers for human intervention.

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