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01.
medRxiv (Medicine) 2026-06-22

Development and validation of a risk prediction algorithm to estimate all-cause mortality among community-dwelling Canadians: the Mortality Population Risk Tool (MPoRT)

BACKGROUND: The risk of all-cause mortality can inform decision-making for chronic disease prevention. We developed a predictive algorithm to estimate the 5-year risk of death among community-dwelling adults. METHODS: We derived and validated the Mortality Population Risk Tool (MPoRT) using data from population health surveys in Canada (the Canadian Community Health Survey) and the United States (the National Health Interview Survey), survey years 2001 to 2011, linked to vital statistics. The outcome was death within five years of the survey response. The algorithm was developed using data from Ontario respondents using a Cox proportional hazards model, then modified and re-estimated to allow cross-national assessment in Canada and the United States. Twenty-three prespecified predictors were assessed: seven sociodemographic, six behavioural, and ten general health and chronic disease. RESULTS: 527,369 respondents aged 20 to 105 years were included in the Canadian and United States development and validation cohorts, with 43,758 deaths during 3.68 million person-years follow-up. The final sex-specific MPoRT algorithms each contained 21 variables, showing strong discrimination (C-statistic: females 0.874 [0.871–0.877]; males 0.867 [0.865–0.871]) and good calibration overall and in 246 of 247 subgroups. Discrimination was modestly attenuated (0.01 decrease in C-statistic) in cross-national validation between Canada and the United States, with good calibration across all 71 subgroups. INTERPRETATION: MPoRT accurately discriminated all-cause mortality using only self-reported data, enabling broad application without clinical measures. While validation outside North America is needed to confirm broader applicability, MPoRT is designed for straightforward recalibration using routinely available national mortality data. This supports targeted chronic disease prevention strategies at both the population and individual levels, though the limitations inherent to self-reported predictors should be considered when interpreting predictions.

02.
arXiv (CS.CV) 2026-06-17

A Quantitative Analysis of Multimodal Biomarkers in Alzheimer's Disease

Despite increasing adoption of multimodal approaches in Alzheimer's Disease (AD) research – aimed at integrating molecular, structural, clinical, and genetic biomarkers to enhance disease characterization – the relationships among these modalities remain poorly understood. A systematic analysis of their dynamic interaction is essential for improving disease modeling, identifying redundant assessments, and reducing patient burden and acquisition costs. In this paper, we present a quantitative analysis of multimodal AD biomarkers by integrating tau-PET, structural MRI, cognitive scores (MMSE and CDR), and APOE4 data from 789 subjects drawn from the ADNI dataset. In our analyses, we (A) quantify cross-modal mutual information and explained variance to assess redundancy and predictive dependencies; (B) examine associations between tau topologies and structural atrophy across brain regions to select informative ROIs; (C) perform a statistical decomposition of the tau-cognition association into atrophy-related and atrophy-independent components; (D) and identify a dominant neurodegenerative trajectory that aligns with cognitive decline. This study provides a systematic characterization of cross-modal relationships, improving the interpretability and selection of biomarkers in AD. Code is publicly available at: https://github.com/antonioscardace/Multimodal-AD.

03.
arXiv (CS.CV) 2026-06-15

CottonLeafVision: An Explainable and Robust Deep Learning Framework for Cotton Leaf Disease Classification

Globally, cotton is a highly economically beneficial crop, as the textile industry heavily depends on it. So, the precise identification and detection of cotton leaf disease is crucial for economic stability. The development goal of "CottonLeafVision" is to accurately classify and detect cotton leaf disease. With this goal, we have evaluated multiple pretrained Deep Convolutional Neural Networks, including DenseNet201, InceptionV3, and VGG19 on a publicly available cotton leaf disease image dataset. This image dataset includes seven classes, six disease classes, and one healthy class, collected under various field conditions reflecting real-world challenges. Among these pretrained models, with DenseNet201, we have achieved the highest classification accuracy of 98%. To enhance the model reliability and interpretability, we have implemented different techniques and methods such as Gradient-weighted Class Activation Mapping (Grad-CAM), occlusion sensitivity analysis and adversarial training to increase the noise resistance of the model. Finally, we have developed a prototype in order to utilize the model's capabilities on real life agriculture. This paper shows the deep learning model's capabilities to classify the disease in real-life cotton disease management situations.

04.
Nature Medicine 2026-06-22

Biological aging and generational shifts in early-onset cancer risk

Authors:

Incidence of early-onset cancer is rising globally in recent generations, which underscores the need to elucidate the influence of emerging generational risk factors. Systemic and organ-specific aging reflects the cumulative impact of exposures and may provide an integrative and complementary approach to understand early-onset cancer risk. Here among 154,169 young adults from the United Kingdom Biobank, systemic aging measured by PhenoAge increased across birth cohorts, with 23% s.d. increase for those born 1965–1974 versus 1950–1954, and was associated with early-onset solid cancer risk (hazard ratio (HR)per s.d. 1.08; 95% confidence interval (CI), 1.03–1.13), driven by lung, gastrointestinal and uterine cancers, independent of genetic risks of aging and cancer. Patterns were consistent using alternative systemic aging measures, including the Klemera–Doubal method-defined age gap and metabolomic-based age gap. These findings were validated partially among 10,262 participants in the United States All of Us Research Program. Proteomics-based organ-specific aging analyses linked immune aging with early-onset lung cancer (HRper s.d. 1.89; CI, 1.20–2.97) and adipose tissue aging to early-onset colorectal cancer (HR 1.60; CI, 1.11–2.32). Greater age gap, reflecting more advanced biological aging relative to chronological age, may serve as a driver associated with risk of early-onset solid cancers, highlighting the importance of uncovering underlying mechanisms to guide effective prevention strategies. Analyses of population cohorts found that young adults exhibited earlier systemic and organ-specific aging, which was associated with increased risk of early-onset cancer compared with older adults born decades earlier.

05.
arXiv (CS.AI) 2026-06-19

Beyond Reasoning Gains: Mitigating General-Capability Forgetting in Large Reasoning Models

arXiv:2510.21978v2 Announce Type: replace-cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has delivered impressive gains in mathematical and multimodal reasoning and has become a standard post-training paradigm for contemporary language and vision-language models. However, the RLVR recipe introduces a significant risk of capability regression, in which models forget foundational skills after prolonged training without employing regularization strategies. We empirically confirm this concern, observing that open-source reasoning models suffer performance degradation on core capabilities such as perception and faithfulness. While imposing regularization terms like KL divergence can help prevent deviation from the base model, these terms are computed on the current task and therefore do not guarantee preservation of broader knowledge. Meanwhile, commonly used experience replay across heterogeneous domains makes it nontrivial to decide how much training emphasis each objective should receive. To address this, we propose RECAP-a replay strategy with dynamic objective reweighting for general knowledge preservation. Our reweighting mechanism adapts online using short-horizon signals of convergence and instability, shifting the post-training focus away from saturated objectives and toward underperforming or volatile ones. Our method is end-to-end and readily applicable to existing RLVR pipelines without training additional models or heavy tuning. Extensive experiments on benchmarks using Qwen2.5-VL-3B and Qwen2.5-VL-7B demonstrate the effectiveness of our method, which not only preserves general capabilities but also improves reasoning by enabling more flexible trade-offs among in-task rewards.

06.
medRxiv (Medicine) 2026-06-22

The direct economic impact of surgical non-response in orthopaedic hip, knee, and spine surgery for osteoarthritis: a cost-utility analysis

Background Annually, nearly 2 million hip, knee, and spinal inpatient surgeries are performed in Canada and the US for osteoarthritis (OA), costing over $37 billion in hospital expenditures. However, 15-30% of patients experience limited or no improvement, resulting in poor value for money. This study evaluated the one-year cost-utility of joint and spine procedures for OA by comparing non-responders to responders, considering various responder definitions. Methods Individual micro-costing data were collected for 1,175 elective hip, knee, and spine patients enrolled in the Longitudinal Evaluation in the Arthritis Program - Osteoarthritis (LEAP-OA) between 2014 and 2018. Quality-adjusted life years (QALYs) were derived using the SF-6D utility index. One-year incremental cost-utility ratios (ICURs) were calculated from the hospital perspective. Results Responder rates varied by definition, ranging from 78%-94% for hip replacements, 64%-90% for knee replacements, 60%-64% for spine fusions, and 50%-68% for spine decompressions. Corresponding ICURs were: $45,956-$51,773/QALY for responders versus $108,593-$485,762/QALY for non-responders for hip replacements; $54,831-$71,151/QALY for responders versus $200,486-$1,203,596/QALY for non-responders for knee replacements; $65,980-$74,422/QALY for responders versus $262,039-$729,686/QALY for non-responders for spine fusions; and $29,947-$42,168/QALY for responders versus $63,195-$662,586/QALY for non-responders for spine decompressions. Conclusions While surgical response rates were highly dependent on the responder definition, ICURs for non-responders were significantly higher than those for responders across all definitions. Beyond the negative impact on patients, there is a compelling economic argument for investment in improved pre-operative identification of patients at risk of surgical non-response. Such efforts could enable more personalized, value-based care pathways and reduce the provision of low-value surgical interventions.

07.
medRxiv (Medicine) 2026-06-18

Diabetes is associated with increased nocturnal respiratory rate

Background and Objective: Diabetes mellitus (DM) causes autonomic neuropathy, which may alter nocturnal respiratory rate (NRR). To test the association between DM and NRR, we analyzed elective polysomnograms of four large observational cohorts. Research Design and Methods: We performed cross-sectional analysis of over 25,000 individuals with polysomnograms (PSGs) from the Sleep Heart Health Study (SHHS), Hispanic Community Health Study/Study of Latinos (HCHS/SOL), Osteoporotic Fractures in Men Study (MrOS), and Wisconsin Sleep Cohort (WSC). Patient-level NRRs were derived from inductance plethysmography waveforms. DM status was determined by self-report, physician diagnosis, medication use, or laboratory values, depending on the cohort. We related DM and NRR (continuous and dichotomized) using logistic regression models and adjusted for potential confounders. Cohort-specific results were combined using random-effects meta-analysis. Results: Meta-analysis of unadjusted models showed a pooled odds ratio (OR) of 1.10 (95% CI:1.04-1.17) for each breath-per-minute (brpm) increase in NRR. This association remained significant after multivariable adjustment (OR:1.06, 95% CI:1.02-1.11). Dichotomized analyses similarly showed higher odds of DM across dichotomization thresholds ranging from 15 to 21 brpm. At a threshold of 18 brpm, the unadjusted pooled OR was 1.77 (95% CI:1.23-2.55, P=0.0022), and the adjusted OR was 1.49 (95% CI:1.10-2.02, P=0.0098). Conclusions: Clinically stable outpatients with elevated NRR have an increased prevalence of DM. Additional studies are needed to investigate whether the mechanism is autonomic neuropathy and whether monitoring NRR can detect early complications of DM.

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

Pre-Training for Simulation-Based Science: A Study on Jet Foundation Model Training Objectives

arXiv:2606.14870v1 Announce Type: cross Abstract: Foundation models (FMs) trained on large datasets and fine-tuned on downstream tasks have emerged as a powerful paradigm in AI for science. Industrial FMs are typically trained using self-supervision with masking due to the lack of labels. In many scientific domains, accurate simulations are plentiful and facilitate large, labeled datasets. This opens up new possibilities for pre-training. We present a systematic comparison of pre-training methods using the OmniLearned High Energy Physics FM framework. We test supervised classification, flow-matching generation, and self-supervised masked particle modeling. All models are pre-trained on the JetClass dataset and fine-tuned on two representative downstream tasks, top jet classification and JetNet conditional generation. Among other observations, for classification tasks, we find that pure classifier pre-training is optimal when downstream labels and model capacity are plentiful, but combining it with self-supervised masked particle modeling (MPM) is uniquely powerful in the low-finetuning label regime. Flow matching-based generative pre-training seems to provide little benefit for downstream classification, and interestingly, for downstream generation, we find that flow matching must be in the pre-training objective to see a significant finetuning advantage, hinting at the orthogonality of classification and generation tasks. That is, for a model to transfer to both generative and classification downstream tasks, it must be pre-trained on both. This study provides a template for controlled scaling analysis of pre-training objectives for foundation models in simulation-based sciences.

09.
arXiv (CS.AI) 2026-06-16

FragFuse: Bypassing Access Control of Large Language Model Agents via Memory-Based Query Fragmentation and Fusion

arXiv:2606.15609v1 Announce Type: cross Abstract: Large language model (LLM) agents increasingly rely on long-term memory to support complex task execution, user personalization, and domain adaptation. Meanwhile, emerging access-control mechanisms for LLM agents are being explored to block policy-violating requests and prevent misuse. We reveal a novel attack surface arising from agent memory operations: prohibited content that would trigger access control can be fragmented across interactions, stored in long-term memory in benign-appearing form, and later reconstructed through memory retrieval without appearing explicitly in the final user query. We propose FragFuse, the first attack that enables unprivileged users to bypass agent access control by exploiting this temporal channel introduced by long-term memory. FragFuse operates in three stages: (1) identifying rejection-responsive fragments via black-box adaptive querying with fragment masking; (2) injecting these fragments into memory using marker carrier queries; and (3) retrieving and fusing the stored fragments through a follow-up attack query. Although FragFuse can be instantiated manually for individual agents, we further develop a surrogate-based optimization scheme that tunes fusion instructions and marker designs, enabling automated attack generation without violating the attacker's threat-model assumptions. We evaluate FragFuse across four representative agent settings and task domains, covering three state-of-the-art agent access-control mechanisms. FragFuse achieves an average bypass success rate of 86.3% and an average end-to-end harmful task success rate of 41.1% across all settings, with only 4.4% average task-success degradation compared with configurations without access control. We also show that alternative defenses, including state-of-the-art prompt-injection detectors and perplexity detectors, do not effectively address this attack.

10.
arXiv (CS.LG) 2026-06-15

Shuttling Compiler for Trapped-Ion Quantum Computers Based on Large Language Models

arXiv:2512.18021v3 Announce Type: replace-cross Abstract: We present the first shuttling compiler based on large language models (LLMs) for trapped-ion quantum computers, where qubits are shuttled between segments for gate execution and qubit storage. We fine-tune pre-trained LLMs on examples from linear and branched one-dimensional shuttling architectures. Thus, we obtain a layout-independent compilation strategy that learns the required shuttling operations directly from data. Using benchmark circuits with up to 16 qubits, such fine-tuned LLMs can now generate valid schedules for shuttling architectures. Notably, we also obtain a valid schedule for a previously unseen four-way junction layout. This demonstrates that trained LLMs can generalize to layouts not encountered during training. For various architectures, LLM-based schedules improve upon state-of-the-art baseline compiler results, reducing the shuttling effort by up to 15%.

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

MooMIns – Monocular 3D Reconstruction and Object Pose Estimation from Multiple Instances

Simultaneous 3D reconstruction and 6D object pose estimation from a single monocular image is an inherently ill-posed problem. In industrial settings, however, multiple instances of an object are often randomly arranged in bins, implicitly providing several views of the same object within a single image. We show that this implicit multi-view geometry can be exploited to simultaneously reconstruct the object in 3D and estimate the 6D pose of each visible object instance. We present MooMIns, a new Gaussian-splatting-based approach that inverts the original Gaussian splatting formulation: instead of rendering a single scene from multiple cameras, we render multiple object instances from a single camera. Our method is initialized with SAM3 instance segmentation masks and a modified Structure from Motion (SfM) pipeline. In contrast to learned monocular depth estimation, we perform true geometry-based reconstruction from image evidence, avoiding hallucinations caused by training data priors. We evaluate MooMIns on synthetic and real bin-picking scenarios, and demonstrate accurate reconstruction of previously unseen objects as well as reliable pose estimation of individual instance

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

Beyond Scalar Distances: Semantic Attribute Gradients from Frozen MLLMs for Visual Embeddings

Vision encoders for retrieval are typically trained with class-label supervision: each training pair reduces to a scalar that uniformly pushes the embedding apart or pulls it together, as if every visual attribute either differed or matched. A multimodal large language model (MLLM), shown the same pair, can articulate those attributes and use them to predict whether the images share a class. We propose SAGA, a framework that turns this language-grounded, attribute-aware perception into a training signal for the encoder itself. Specifically, we use Group Relative Policy Optimization (GRPO) to reward the MLLM for correct predictions on the vision encoder's tokens. Since correct predictions require those tokens to expose the specific attributes that differ or match between the pair, the gradient pushes the encoder to encode them, replacing the uniform pair-level scalar with attribute-resolved supervision. An auxiliary attention-distillation loss anchors the encoder's embedding to tokens the MLLM attended to, and a standard metric-learning loss shapes the embedding geometry for nearest-neighbour retrieval. The MLLM is frozen throughout and discarded at inference, matching the deployment cost of a metric-learning baseline. SAGA improves Recall@1 by 3 to 6 points over state-of-the-art baselines on CUB-200-2011, Cars-196, FGVC-Aircraft, and iNaturalist Aves on zero-shot image retrieval.

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

Smoothing Dark Areas in Molecular Latent Diffusion

arXiv:2606.13955v1 Announce Type: new Abstract: Latent diffusion is a promising framework for scalable 3D molecular generation, but it requires a latent space that remains smooth, valid, and navigable beyond posterior samples. Existing molecular VAEs, however, are typically learned through reconstruction-based objectives, which do not guarantee such a latent space. We show that this leads to dark areas: regions of latent space that are reachable during diffusion sampling but decode to disconnected or chemically invalid molecules. Unlike in image generation, molecular decoding requires strict structural and chemical precision, so even small latent perturbations can produce catastrophic failures. We therefore propose TopVAE, a topology-optimized VAE that reduces dark areas by making the decoder internalize structural and chemical constraints during training, eliminating the need for test-time chemical correction. TopVAE greatly improves off-posterior robustness, and when paired with a standard DiT, achieves $77\%$ lower FCD-3D on QM9, the highest V&C, $52\%$ lower FCD-3D on GEOM-Drugs, and $1.29{\times}$ more stable and connected molecules on zero-shot scaffold inpainting.

14.
arXiv (CS.LG) 2026-06-16

Factorized Neural Operators Decompose Dynamic and Persistent Responses

arXiv:2606.16900v1 Announce Type: new Abstract: Physical systems often exhibit heterogeneous mechanisms, where rapidly evolving dynamics coexist with persistent structures. Capturing such multiscale physical behavior remains challenging for existing neural operators, which typically rely on single dominant inductive bias and therefore couple distinct physical responses into a shared representation. We introduce the Unified Green's Function Framework across domains and propose the Factorized Neural Operators (FaNO), which decompose spectral representations into equivariant dynamic responses and invariant persistent responses, leading to better interpretability and generalization. Mechanistically, we show that the two operator branches spontaneously specialize into distinct physical roles that remain consistent across scales and domains: the equivariant branch captures rapidly varying transient dynamics, whereas the invariant branch extracts coherent persistent structures. This factorized mechanism of FaNO improves prediction accuracy, parameter efficiency and cross-scale generalization across physical systems and domains. In particular, it maintains consistent predictions under long-horizon autoregressive rollout, cross-resolution extrapolation and physical-regime shifts. These findings suggest that scalable physical modeling may benefit from moving beyond single-inductive-bias formulations toward factorized operator representations that better reflect the heterogeneous organization of physical systems, accelerating the reliable deployment of machine learning for scientific computing and discovery.

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

Mask-Proof: An LLM-based Automated Data Curation Pipeline on Mathematical Proofs

arXiv:2606.15258v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly capable of mathematical problem solving and can even assist with research-level proofs, yet we still lack a scalable and reproducible way to measure step-level reasoning in long proofs across diverse sources. This evaluation gap limits trustworthy AI assistance in proof-certified scientific progress. Existing evaluations often emphasize final answers or rely on costly expert grading, while end-to-end proof generation remains open-ended and hard to verify automatically. We introduce Mask-Proof, a pipeline that turns real proofs into automatically checkable masked-step tasks. It masks key formula steps, provides the necessary surrounding context, and evaluates model reconstructions with an LLM-based equivalence judge using repeated votes for stability. The resulting Mask-ProofBench contains 292 curated problems across diverse research areas. Experiments with 17 models show that reasoning-enhanced models outperform standard models by 12% to 27%. Our evaluator achieves 96.8% agreement with expert annotators, enabling faithful, reproducible, and comparable measurement of step-level mathematical reasoning. Benchmark, annotations, and code are available at https://github.com/weating/Mask-Proof.

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

Fi-Gaussian: Frequency-Aware Implicit Gaussian Splatting for Single Image Dehazing

Single image dehazing continues to be hindered by the loss of high-frequency details and the difficulty of accurate physical scattering modeling. To address these issues, we propose Fi-Gaussian, a frequency-aware implicit Gaussian splatting network for single image dehazing. Unlike explicit rendering methods that rely on 3D point clouds, our method employs implicit Gaussian splatting to adaptively model the underlying distribution of clear images as a continuous representation in 2D feature space. The core of the network is a frequency-aware implicit Gaussian splatting module, which decouples low-frequency structural information and high-frequency texture information in the frequency domain and then performs adaptive Gaussian aggregation with complex-valued weights to recover fine details. In addition, a physics-driven scattering renormalization mechanism is introduced to estimate the transmission map and atmospheric light under the guidance of implicit Gaussian priors. Extensive experiments on multiple benchmark datasets demonstrate that Fi-Gaussian achieves state-of-the-art quantitative performance and produces visually superior dehazed results, validating the effectiveness of implicit Gaussian splatting for low-level vision tasks.

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

ERN-Net : Evolving Reason Node-Net for Document Binarization

This paper presents ERN-Net, an Evolving Reason Node-Net for efficient document image binarization. ERN-Net enhances degradation-sensitive regions, such as faint strokes, broken characters, and noisy backgrounds, through evolving reason nodes and multi-scale reasoning. We further compare ResNet-101, ConvNeXt-Tiny, and ConvNeXt-Base, and find that ConvNeXt-Tiny provides the best practical trade-off between accuracy and memory usage. In addition, DIBCO-based pretraining improves binarization performance without increasing model memory consumption, requiring only about 1.5 additional training hours. Experiments on DIBCO-style benchmarks show that ERN-Net is effective under low-data and low-memory settings.

18.
Nature Biotechnology 2026-06-19

Efficient site-specific gene addition using R2 retrotransposons in tobacco and rice

Authors:

Precise integration of multikilobase DNA fragments remains a major technical barrier in plants. Here we introduce non-long terminal repeat (non-LTR) R2 retrotransposons as a versatile system for targeted gene integration in plants. We reconstituted R2 activity in Nicotiana benthamiana and benchmarked insertion efficiency and fidelity using a TMV-based episomal reporter system. We demonstrate site-specific integration of GFP (2.2 kb) and recombinase-compatible landing pads (0.6 kb) into 28S rDNA arrays, with intact cassette insertion frequencies up to 75% and 53%, respectively. To temporally constrain donor availability and avoid DNA intermediates, we combined in planta effector expression with recombinant RNA virus-mediated donor delivery. We apply R2 retrotransposons for targeted insertion of resistance cassettes within the rDNA of rice callus, achieving integration efficiencies up to 17%. These results position R2 retrotransposons as a double-strand break-free system for RNA-templated insertion of multikilobase gene cassettes at rDNA loci, for safe-harbor trait stacking in plants with potential applications in crop improvement and synthetic biology. Retrotransposons are applied in plants for safe-harbor transgene integration.

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

MVEB: Massive Video Embedding Benchmark

We introduce the Massive Video Embedding Benchmark (MVEB), a 23-task benchmark for video embeddings spanning classification, zero-shot classification, clustering, pair classification, retrieval, and video-centric question answering. We evaluate 33 models and find that no single model dominates: MLLM-based embeddings lead on classification, clustering, pair classification, and QA; multimodal binding leads on retrieval and zero-shot classification; generative MLLMs without contrastive adaptation collapse on cross-modal tasks. Paired video-only vs. audio+video evaluations show that audio's contribution depends on dataset annotation provenance: audio helps when labels were produced from both modalities and hurts when they were produced from visuals alone, a six-point gap consistent across model families. MVEB is derived from MVEB+, a 184-task pool, and is designed to maintain task diversity while reducing evaluation cost. It integrates into the MTEB ecosystem for unified evaluation across text, image, audio, and video. We release MVEB and all 184 tasks along with code and a leaderboard at https://github.com/embeddings-benchmark/mteb.

20.
bioRxiv (Bioinfo) 2026-06-19

Identification of Altered Potassium Channels for Drug Repurposing in Long COVID Patients

Long COVID (LC) is a complex condition characterized by persistent, chronic multisystem manifestations, with a significant proportion of patients exhibiting neurological symptoms. Human ion channels (HICs), particularly potassium channels, are abundantly expressed in the nervous system and linked to key metabolic processes, making them potential candidates for understanding LC pathophysiology and drug repurposing. Meta-analysis of RNA-Seq datasets from COVID-19 recovered and LC patients was performed to identify altered HICs in LC. Differential gene expression analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) were performed to uncover key genes, pathways, and co-expression modules consisting of HICs, lipid metabolism-, and immune signaling-related genes. Drug-gene interaction analysis was performed to identify approved drugs targeting potential HICs. A total of 715 dysregulated genes, including eighteen HICs were identified, among which seven were potassium channels. Three significant modules containing HICs, lipid metabolism-, and immune signaling-related genes were identified and found to be associated with antigen processing and presentation, complement and coagulation cascades, and cytokine-related pathways. Approved drugs targeting KCNA6, KCNJ10, KCNN3, and KCNH4 were identified. With further experimental validation, these dysregulated potassium channels, supported by their co-expression networks and pathway associations, may act as potential candidates for drug repurposing in LC patients.

21.
arXiv (CS.CL) 2026-06-11

System Report for CCL25-Eval Task 5: New Dataset and LoRA-Fine-Tuned Qwen2.5

Authors:

Recently, large language models (LLMs) have achieved promising progress in the fields of classical Chinese translation and the generation of classical poetry. However, domain-specific research on precise translation and affective-semantic understanding of classical poetry remains limited. The main challenge is that most studies treat the poetic appreciation task as a general-domain problem, neglecting the distinctive features of poetic appreciation, while high-quality and domain-specific datasets are extremely limited. To address this limitation, we decompose the task into three subtasks: term interpretation, semantic interpretation, and emotional inference. Based on multiple open-source datasets, we perform data cleansing and alignment to construct the Classical Chinese Poetry Instruction Pair Dataset (CCPoetry-49K), which comprises 49,404 high-quality instruction-response pairs explicitly optimized for this domain. We then propose a domain-specialized LLM, called PoetryQwen, by applying Low-Rank Adaptation (LoRA) to fine-tune the Qwen2.5-14B model. Experimental results on the CCL25-Eval Task 5 benchmark demonstrate that PoetryQwen achieves a score of 0.757, representing a 9.7% improvement over the Qwen2.5-14B-Instruct baseline (0.690). These findings clearly indicate that PoetryQwen significantly enhances performance in precise translation and emotional understanding of classical poetry. We present new dataset and methodological considerations intended to support the domain-specific optimization of LLMs.

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

RePAIR: Predictive Self-Supervised Representation Learning in Chess

arXiv:2606.11860v1 Announce Type: new Abstract: In this paper, we introduce Representation Prediction via Autoencoding using Iterative Refinement (RePAIR) - a novel self-supervised representation learning architecture that synthesizes Masked Autoencoders (MAE), Joint Embedding Predictive Architectures (JEPA), and Bidirectional Encoder Representations from Transformers (BERT). We demonstrate how it can be used to encode objects in sequential data like consecutive chess positions into compact yet meaningful representations. The basic principle of the architecture is to mask large portions of a sequence of latent states, similar to BERT and MAE. Then, we apply a lightweight Predictor to the latent representations that repairs gaps in the sequence in a lower-dimensional embedding space akin to JEPA. Our experiments in the domain of chess show that the Encoder refines the board representations such that meaningful chess concepts emerge clustered in the latent space. Furthermore, reconstructions of the masked board states show that the model is able to reason about the piece movements without relying on costly reinforcement learning methods. Lastly, we find that the resulting representation space allows for quick and intuitive dissections of chess games by observing the game path trajectories in this semantically rich space.

23.
medRxiv (Medicine) 2026-06-22

Spatial Analysis and Multilevel Determinants of Hypertension in Zambia: Analysis of the 2017 WHO STEPS Survey

Background: Hypertension is the leading modifiable cardiovascular risk factor globally, with the fastest-growing burden in low- and middle-income countries. This study aimed to estimate national hypertension prevalence, map provincial patterns, assess spatial clustering, and identify individual and community-level determinants among Zambian adults using the 2017 WHO STEPS survey. Methods: This cross-sectional study used data from the 2017 WHO STEPS survey, a nationally representative sample of 4,301 adults aged 18-69 years. Hypertension was defined as systolic BP [&ge;]140 mmHg, diastolic BP [&ge;]90 mmHg, or current antihypertensive use. Spatial autocorrelation was assessed via Moran's I and LISA. Four nested generalised linear mixed models with PSU-level random intercepts identified individual and community-level determinants. Results: Overall weighted hypertension prevalence was 24.0%. Lusaka recorded the highest prevalence (30.2%), followed by Southern (29.9%) and Muchinga (28.3%) provinces; Western Province had the lowest (12.4%). Spatial clustering was statistically significant but modest (Moran's I = 0.0247, p < 0.001). Between-cluster variation reduced from ICC = 5.9% to 1.8% in the full model, indicating geographic differences were largely explained by individual characteristics. Age was the strongest predictor; adults aged 60-69 had nearly sevenfold higher odds than those aged 18-29 (AOR 6.92, 95% CI: 4.95-9.66). Women had lower odds than men (AOR 0.64, 95% CI: 0.52-0.79). Obesity (AOR 2.34), overweight (AOR 1.65), high cholesterol (AOR 1.40), diabetes (AOR 1.35), and single marital status (AOR 1.34) were independently significant. Western Province showed consistently lower odds than Central Province (AOR 0.48). Conclusion: Hypertension affects one in four Zambian adults, driven primarily by age, sex, obesity, dyslipidaemia, and diabetes. Geographically prioritised interventions, including community health worker-led screening programmes in Lusaka and Southern Province, would maximise population-level impact. Population-level salt reduction and alcohol policies represent cost-effective complementary strategies. Longitudinal studies with finer spatial resolution are needed to clarify causal pathways underlying observed geographic clustering and inform SDG Target 3.4 progress.

24.
arXiv (CS.AI) 2026-06-17

Querying an astronomical database using large language models: the ALeRCE text-to-SQL system

arXiv:2606.18108v1 Announce Type: cross Abstract: We develop a text-to-SQL (structured query language) system based on large language models (LLMs) using in-context learning and apply it to the Automatic Learning for the Rapid Classification of Events (ALeRCE) astronomical database. ALeRCE is a community broker for the Zwicky Transient Facility and the Vera C. Rubin Observatory. The system enables users to query the database in natural language (NL) and generates executable SQL queries. To develop and evaluate the system, we constructed a dataset of 110 NL/SQL pairs. We propose a step-by-step generation framework comprising four modules: schema linking, query classification, prompt decomposition, and self-correction. The performance of thirteen LLMs is evaluated using in-context learning and prompt engineering techniques. Text-to-SQL performance is assessed using the perfect-match (PM) rate for row identifiers (e.g., object identifiers) and column identifiers (i.e., column names). The proposed step-by-step framework consistently outperforms a direct-inference baseline, while the self-correction module consistently reduces execution errors. For Claude Opus 4.6, PM performance on row (column) identifiers is high for simple queries, reaching 0.97 (0.94), and decreases with query complexity to 0.44 (0.72) for medium queries and 0.59 (0.49) for hard queries. Among the thirteen evaluated models, the best-performing LLMs for the text-to-SQL task are Claude Opus 4.6, Gemini 2.5 Pro, Gemini 3 Flash, and GPT-5.2-Codex.

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arXiv (quant-ph) 2026-06-15

Interpreting Bohm-like quantum potentials in "Computing quantum waves exactly from classical action"

arXiv:2605.20443v3 Announce Type: replace Abstract: The recent posting arXiv:2605.02621 [14], commenting on the article rspa.2025.0413 [7], argues that the proof of Lemma 3.1 in [7] is missing the spatial derivative of the density, which would lead to a Bohm-like quantum potential. This technical note shows why the propagated density is independent of space in the Feynman propagator construction of Lemma 3.1. This is done by extending the proof of Lemma 3.1 explicitly with Bohm-like quantum potential terms along the stationary action paths, and then showing that these terms are exactly zero. In [7], this property can also be verified directly on most examples (double slit, Aharonov-Bohm, potential well, harmonic oscillator, tunneling, EPR, QED), as well as in the derivations of the Pauli, Dirac, and Maxwell equations. For more general nonlinear actions, a time rescaling may be required to guarantee this space independence along stationary paths. In the hydrogen atom example, this time rescaling can be computed in closed form. In contrast to the general wave of the Madelung solution [9] Lemma 3.1 of [7] is defined first for a propagator, and a general wave is then constructed in a second step. Recall that a propagator is a specific quantum wave, which is initialized at $t=0$ with a Dirac impulse at a given initial position or momentum. In turn, a general wave is constructed in a second step by superposing a distribution of initial conditions using the propagator. This key difference is why the Bohm-like quantum potential terms disappear in the construction [7] (specifically, in the first step) while the Bohm potential in the Madelung analysis does not. This fundamental difference is also consistent with the fact that the wave construction in [7] extends naturally to relativistic contexts, while Bohmian non-locality notoriously prevents such extensions. Keywords - Response to arXiv:2605.02621, in relation to rspa.2025.0413