TB vaccine from the 1920s shows promise in diabetes trial
The shot reduced insulin use for people with type 1 diabetes and another autoimmune condition. The shot reduced insulin use for people with type 1 diabetes and another autoimmune condition.
Academic Intelligence · Curated Daily
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The shot reduced insulin use for people with type 1 diabetes and another autoimmune condition. The shot reduced insulin use for people with type 1 diabetes and another autoimmune condition.
Self-supervised video representation learning has recently advanced through contrastive learning, masked reconstruction, and predictive representation learning. Reconstruction-based approaches such as MAE and VideoMAE learn representations by recovering masked visual content [he2022mae,tong2022videomae], while contrastive methods such as CLIP learn semantically meaningful embedding spaces through representation alignment [radford2021clip]. In this work, we introduce a Momentum-Guided Semantic Forecasting framework (MoFore) for self-supervised video representation learning. Instead of optimizing for pixel-level reconstruction or task-specific semantic alignment, the proposed method learns temporally predictive video representations by forecasting future latent embeddings from temporally distant context clips. To improve robustness across temporal scales, we further introduce randomized temporal-gap forecasting during training. The framework combines predictive latent forecasting with contrastive regularization to encourage temporal consistency while preventing representation collapse. Experiments on the UCF101 dataset demonstrate that the proposed framework learns temporally consistent and semantically meaningful video representations without using action labels during training. Quantitative analysis shows strong temporal stability and emergent category-level structure in the learned embedding space, while qualitative retrieval experiments reveal motion-aware organization across related activities. Overall, the results suggest that long-range latent forecasting provides an effective and computationally efficient approach for self-supervised video representation learning without relying on reconstruction-based objectives.
Computational antibody design methods can generate large libraries of candidate binders for a target epitope, but prioritizing which candidates to test experimentally remains a major bottleneck. Existing scoring approaches, including physics-based affinity estimators, structure-prediction-derived confidence measures, and inverse-folding likelihood models, provide useful proxy signals but are not explicitly optimized for early enrichment of binders among many structurally similar candidates. Here we investigate epitope-conditioned antibody binder ranking as a dedicated learning problem and introduce AGZArank, a geometric deep learning framework trained with structure-derived synthetic supervision based on normalized pseudo-energy targets. On a benchmark of 45 experimentally validated antibody-antigen interfaces, AGZArank recovered the true binder within the top ten candidates in 44.4% of cases and showed stronger generalization on post-2021 structures than ProteinMPNN, ESM-IF, and PRODIGY. Ablation experiments indicate that ranking performance depends primarily on training scale and alignment between the optimization objective and retrieval-based evaluation, rather than architectural complexity alone. These results support candidate prioritization as a distinct and tractable problem in computational antibody design.
arXiv:2606.18089v1 Announce Type: new Abstract: Post-training pipelines that combine supervised fine-tuning (SFT) with reinforcement learning (RL) have emerged as the key recipe for transforming large language models (LLMs) into robust reasoners. We argue that this combined success is driven by compositional generalization, which we formalize through a hierarchical latent selection model. In this framework, reasoning traces are generated by a cascade of discrete latent selection variables corresponding to reusable atomic modules, including both skills (local operations) and routing mechanisms (how intermediate information is selected, reused, and composed). Within this model, we theoretically show that SFT and RL play asymmetric, complementary roles: SFT supplies the raw module materials in compositional traces, and RL decomposes those traces to identify the latent atomic modules and enable compositional generalization. We design controlled experiments to validate this theory. Our results demonstrate that RL can extract atomic modules from compound traces supplied by SFT and recombine them to solve new configurations. Moreover, we find that training on compound traces yields stronger generalization than training on isolated atomic modules. Finally, we investigate the relationship between SFT and RL data and identify an effective protocol in which SFT ensures coverage of all atomic modules through compositional traces, while RL focuses on novel compositions outside the SFT support to drive exploration.
Foundation models learned from single-cell transcriptomes are central to the prospect of AI virtual cell that can represent, query and predict cellular state. However, most current single-cell foundation models learn from a single view of gene expression and are optimized primarily through reconstruction or next-token prediction. As a result, they capture expression abundance but can-not explicitly reconcile complementary views of cellular state. Here we present CellOS, a multi-view foundation model that learns cellular representations from paired expression and perception views. CellOS integrates complementary views through a scalable three-stage training strategy that combines causal cell-sentence language modelling, function-preserving dense-to-mixture-of-experts expansion and latent-space alignment via an LLM-JEPA objective. Using this framework, we trained a 12-billion-parameter model on 390.5 million single-cell transcriptomes. Across diverse benchmarks spanning cell-state annotation, batch integration and perturbation-response prediction, CellOS consistently outperformed state-of-the-art single-cell foundation models in cell-state annotation and perturbation-response prediction while preserving robust batch integration. Together, these results suggest that predictive alignment between complementary cellular views provides a scalable path toward representation-centric cellular world models and transferable AI virtual cells.
arXiv:2606.15834v1 Announce Type: new Abstract: The computer systems community has recently seen growing interest in AI-driven system evolution, where AI agents iteratively rewrite systems. Frameworks such as AdaEvolve and Engram report 12-60% score improvements over human-designed algorithms. While these results are promising, there are practical concerns if these AI-evolved programs can perform worse on unseen workloads and exhibit scalability regressions. Given the speed and scale of AI-generated code, we need automated mechanisms to uncover such identify hidden weaknesses in AI-evolved systems programs. To this end, we develop AIChilles that takes as input a baseline program $P$ and an AI-evolved program $P'$, AIChilles searches for valid workloads where $P'$ regresses relative to $P$ in correctness, runtime, memory usage, or output quality. To tackle the diversity in system applications, weakness types and potential bugs, AIChilles combines deterministic workload-parameter extraction, agent-based constraint inference, differential oracles, and code-frequency coverage to discover diverse failures. Across five system applications and 30 AI-evolved programs, AIChilles finds 49 distinct hidden weaknesses. We also show that explicitly including AIChilles in the AI-driven development lifecycle can mitigate several of these weaknesses.
Vision-language models (VLMs) often generate fluent but visually unsupported descriptions, especially by mentioning objects absent from the image. We propose QK Product Steering, a data-free, training-free, and zero-inference-cost weight edit for reducing object hallucination. The method directly edits the per-head query-key product, the operator that produces pre-softmax attention logits, by suppressing a small number of dominant singular modes in selected middle layers. The edited product is then mapped back to the query weights through a closed-form query-only update while keeping shared key weights fixed, making the edit compatible with grouped-query attention. We further decompose the QK product into symmetric and antisymmetric components to distinguish mutual content-similarity patterns from directional attention patterns. Across three GQA-based VLMs, QK Product Steering achieves an average relative CHAIR$_s$ reduction of $4.0\%$, while matched random-mode controls show negligible change. Interpretability ablations show that the hallucination signal is specific to dominant QK modes and is primarily localized to the symmetric mutual-attention channel. Overall, QK Product Steering offers a simple alternative to decoding-time mitigation, requiring no additional data, fine-tuning, or inference-time overhead while largely preserving general multimodal capability.
Text-to-video retrieval in operating rooms (OR) is an enabling technology for OR safety, as it allows stakeholders to retrieve and inspect recordings of specific events. However, because the most safety-critical events may not follow the common structure, to unlock its full potential text-to-video retrieval must be able to handle implicit queries that require reasoning to identify the right video (e.g., the step right before clipping). However, existing methods rely on global embeddings that cannot reason over such queries. We propose OR3, a text-to-video retrieval method that converts clips into action-driven digital twins (ActDTs), grouping concurrent subject-action-object triplets under non-overlapping temporal intervals. Moreover, rather than cross-modal matching through paired encoders, OR3 performs imagination-based retrieval where an LLM generates hypothetical ActDTs from queries. This enables intra-modal matching via a single encoder trained with ActDT-tailored hard negatives. Finally, evidence-grounded refinement revises imagined ActDTs based on discrepancies with top candidates to capture procedure-specific patterns. We construct a benchmark from MM-OR with 276 implicit queries across four reasoning categories over 386 clips from robotic knee procedures. OR3 achieves 57.6 R@1 and 77.3 R@5, outperforming the strongest baseline. These results demonstrate that OR3 enables fine-grained discrimination between visually similar OR video clips through temporal action reasoning.
arXiv:2111.05385v3 Announce Type: replace Abstract: Obesity is a major health problem, increasing the risk of various major chronic diseases, such as diabetes, cancer, and stroke. While the role of obesity identified by cross-sectional BMI recordings has been heavily studied, the role of BMI trajectories is much less explored. In this study, we use a machine-learning approach to subtype individuals' risk of developing 18 major chronic diseases by using their BMI trajectories extracted from a large and geographically diverse EHR dataset capturing the health status of around two million individuals for a period of six years. We define nine new interpretable and evidence-based variables based on the BMI trajectories to cluster the patients into subgroups using the k-means clustering method. We thoroughly review each cluster's characteristics in terms of demographic, socioeconomic, and physiological measurement variables to specify the distinct properties of the patients in the clusters. In our experiments, the direct relationship of obesity with diabetes, hypertension, Alzheimer's, and dementia has been re-established and distinct clusters with specific characteristics for several of the chronic diseases have been found to be conforming or complementary to the existing body of knowledge.
arXiv:2606.20387v1 Announce Type: new Abstract: We investigate how interaction geometry shapes the low-energy phases of sparse tunable long-range quantum models. We focus on a class of graphs whose degree grows logarithmically with system size, and show how symmetry and frustration in graph connectivity can drive, suppress, and reshape ground-state phase transitions. The central examples are power-of-$p$ graphs, where even and odd values of $p$ exhibit qualitatively distinct behaviour: even-$p$ graphs inherit the rich phase structure of the power-of-two model, while odd-$p$ graphs are governed by geometric frustration. Fibonacci graphs provide a contrasting case, lacking the discrete self-similarity of the power-of-$p$ family but exhibiting a direct geometric mapping between the short- and long-range limits. Across our models, we find that phase structure and criticality are governed by the same effective-geometry principle, unifying our framework for experimentally motivated long-range quantum systems.
Purpose: To evaluate the efficacy of large language models (LLMs) in extracting medication-related information from glaucoma clinical notes in the electronic health record (EHR). Design: Cross-sectional. Subjects: 1,250 subjects in the Bascom Palmer Ophthalmic Repository. Methods: Extracted clinical notes from glaucoma-related encounters between 2014 and 2024 were labeled by two glaucoma specialists with a third serving as an adjudicator. Graders were asked to label current topical medications (CTM), proposed changes to topical medications ({Delta}TM), current oral medications (COM), and proposed changes to oral medications ({Delta}OM) in a structured fashion. The dataset was split into development (10%), validation (10%), and test (80%) sets stratified by clinician. Development and validation sets were used to engineer and refine prompts, and the held-out test set was used for model assessment. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT 5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Microsoft Azure AI Foundry within a HIPAA-compliant environment. Inter-grader agreement was assessed with Gwet AC1. LLM performance was initially assessed in a binary fashion with F1 scores, and the degree of text match among positive cases was evaluated using exact match accuracy and Jaccard Index (JI). Main Outcome Measures: F1 score, exact match accuracy, JI. Results: Gwet AC1 for intergrader agreement was 0.799, 0.888, 0.985, and 0.988 for CTM, {Delta}TM, COM, and {Delta}OM, respectively. F1 scores for CTM were 0.985, 0.971, 0.978, 0.968, and 0.970 for Claude, Deepseek, GPT, Grok, and Qwen, respectively; for {Delta}TM: 0.905, 0.826, 0.897, 0.842, 0.855, respectively; for COM: 0.923, 0.887, 0.899, 0.906, 0.894, respectively; for {Delta}OM: 0.958, 0.815, 0.937, 0.835, 0.940, respectively. Among positive cases, range of exact match accuracies for CTM (N=1354) was 0.730- 0.882 and range of JIs was 0.809-0.918. For {Delta}TM (N=404), exact match accuracy range was 0.619-0.780 and JI range was 0.668-0.827. For COM (N=47), exact match accuracy range was 0.766-0.872 and JI range was 0.765-0.870. For {Delta}OM (N=25), exact match accuracy range was 0.583-0.920 and JI range was 0.583-0.922. Conclusions: The GLLaucoMed pipeline demonstrated high performance in extracting and standardizing medication data from unstructured clinical notes, including both current medications and proposed changes. Claude and GPT exhibited the strongest performance.
AI systems based on artificial neural networks are being developed with aspirations of pushing the boundary of human mathematical knowledge. A key question for these systems is how much they can reach beyond their training data. Mathematical discovery requires a strong form of out of distribution generalization; the ability to hypothesize genuinely new - and potentially logically more powerful - mathematical structures. It has been hypothesized that language abilities support such generalizations in human cognition. In this work, we use simple arithmetic as a case study for examining how modern AI models could expand their mathematical horizons, evaluating whether these models can independently discover the concept of "zero". We show that We show that (1) language models of a GPT-2 size are unable to perform this generalization at test time regardless of language pretraining, but (2) models can improve substantially after training on tens or hundreds of examples of zero. Additionally, we find that language pretraining reduces the number of required examples by approximately $50\%$, showing that language abilities can scaffold mathematical discovery in neural models.
arXiv:2605.26631v2 Announce Type: replace-cross Abstract: We propose KO-PDE-IDENT, a data-driven framework for identifying parsimonious partial differential equations (PDEs) with false discovery rate (FDR) control. PDE discovery from noisy observations is often hindered by extreme multicollinearity among candidate terms, which causes typical sparse-regression methods to select spurious terms. To address this problem, KO-PDE-IDENT initially mines a support set of potential candidate terms via model-X knockoff filters with finite-sample FDR control, then refines and ranks the surviving PDE alternatives. The framework integrates three components. First, knockoff feature statistics are constructed by coupling $\ell_{0}$-constrained adaptive best-subset selection with SHapley Additive exPlanations (SHAP), yielding an effective and computationally efficient difference statistic. Second, a recursive feature elimination (RFE) procedure removes terms whose marginal contributions are dispensable and assesses statistical necessity through knockoff-perturbed hypothesis testing. Third, the final model selection is formulated as a multi-criteria decision-making (MCDM) problem, where the optimal governing equation is the alternative that best balances a wide range of criteria such as predictive accuracy, model complexity and coefficient uncertainty. We evaluate KO-PDE-IDENT on five canonical PDEs under severe noise corruption. Empirical results show that our framework can exactly recover the true PDE structure, eliminating false discoveries while retaining all true underlying terms, with low coefficient estimation error.
Genome assembly is a computational pipeline designed to reconstruct chromosomes from small sequencing reads. Following their assembly, contiguous sequences (contigs) are arranged into chromosome-long sequences during scaffolding. Hi-C, a long-range linkage information between regions of the genome widely used in recent large sequencing projects, is often required to correctly order contigs. Several tools have been developed to automate this task following either statistical or deep-learning approaches. Statistical approaches summarise 2D Hi-C matrices into contact densities across sequences, thus ignoring informative visual patterns. The sole existing deep-learning tool uses a transformer-based computer vision model to correct the assembly. It has been trained on several species and uses Hi-C matrices directly. Yet it comes as a supplementary step in the scaffolding process, introducing extra computation time, and has been trained on a dataset that might contain labelling errors, which could provide sub-optimal results. We propose SPA-C, an hybrid pipeline combining the strengths of both approaches. Linkage prediction is handled with a frugal CNN-based model and a graph-solving algorithm is used to generate the scaffolds. Through our input's design, the model is able to both correct errors within assemblies and link contigs, leveraging small, local Hi-C contact matrices. We handled low-complexity regions that might induce erroneous predictions using an external tool, improving the overall accuracy of generated assemblies. On a benchmark of six various genomes and four standard metrics, SPA-C outperformed four out of four state-of-the-art methods while achieving comparable start-to-end computation time.Python and Bash scripts are available on GitHub (https://github.com/SPA-C/SPA-C.git) and Zenodo (https://doi.org/10.5281/zenodo.19000361).
Background. Chronic kidney disease (CKD) affects 10-13% of adults worldwide but remains largely undiagnosed until advanced stages. Hospitalization provides an opportunity for early detection through opportunistic urine albumin-to-creatinine ratio (UACR) measurement. Methods. We conducted a prospective three-arm study of opportunistic CKD screening in general internal medicine wards at Hadassah Mt. Scopus (MS), Hadassah Ein Kerem (EK), and Shaare Zedek Medical Center (SZMC) in Jerusalem (Protocol HMO-23-0300). Adult inpatients without known CKD or recent UACR were enrolled. Pathological UACR was defined as [≥]30 mg/g. Confirmed CKD required two pathological measurements [≥]90 days apart (KDIGO-compatible). eGFR was computed using the 2021 CKD-EPI race-free equation. Pooled proportions were estimated by fixed-effects logit meta-analysis; odds ratios by DerSimonian-Laird random-effects models. Results. A total of 158 patients were enrolled (MS n=50, EK n=57, SZMC n=51). Pathological first UACR was identified in 43/158 patients (27.2%; 95% CI 21.3-34.1%; I2=0% across centers). Of 24 patients with a second UACR available, 14 (58%) confirmed CKD, yielding a pooled confirmed-CKD rate of 8.9% of all screened patients. In-hospital mortality was significantly higher among patients with pathological UACR (9.3% vs ~2%; Fisher's exact p=0.012). In per-center multivariate logistic regression, three predictors reached pooled significance: BUN (OR 1.10 per mg/dL, 95% CI 1.04-1.17, p=0.002, I2=0%), heart failure (OR 3.21, 95% CI 1.34-7.70, p=0.009, I2=0%), and diabetes mellitus (OR 2.54, 95% CI 1.11-5.82, p=0.028, I2=17%). Cardiac/vascular admissions had the highest pathological UACR rate (~42%); GI/hepatic admissions had 0%. Conclusions. Opportunistic inpatient UACR screening identifies previously unrecognized CKD in approximately 9% of general internal medicine patients, with consistent results across three independent centers. BUN elevation, heart failure, and diabetes are the strongest independent predictors. Pathological UACR carries significant short-term mortality risk, supporting integration of routine screening into inpatient care pathways.
Diffusion large language models promise parallel token generation, yet inference remains bottlenecked by deciding which masked tokens can be safely committed together. Fast-dLLM addressed this with KV caching and confidence-guided parallel decoding, but its decoding theory uses a homogeneous high-confidence assumption that effectively reduces each candidate set to its weakest selected token. We argue that this leaves speed on the table because real decoding steps exhibit heterogeneous confidence profiles. We propose Fast-dLLM++, a training-free extension that introduces Fr\'{echet profile decoding}: selecting parallel commit sets from the full sorted confidence profile rather than a single worst-case confidence. The resulting rule is a heterogeneous-confidence generalization of Fast-dLLM's factor selector and it recovers the previous rule exactly in the equal-confidence case and adds a provable heterogeneity bonus when the selected tokens have uneven confidences. Fast-dLLM++ leaves the model, diffusion process, and cache implementation entirely unchanged, making it a drop-in replacement for existing Fast-dLLM decoding. Experiments on GSM8K, MATH, HumanEval, and MBPP with the LLaDA-8B model show that the theoretical improvement translates directly into empirical gains: profile-aware selection improves the accuracy–throughput frontier by exploiting safe parallelism that weakest-token rules miss, achieving up to 37\% higher throughput at comparable accuracy. Our code release is at https://github.com/Ringo-Star/FastdLLM_plusplus.
Dexterous robotic hands are expected to perform complex, contact-rich object manipulation, but learning such skills remains challenging because high-dimensional hands require high-fidelity demonstrations. Imitation learning provides a practical route for acquiring dexterous manipulation skills from human demonstrations, yet collecting synchronized multimodal demonstrations with accurate hand actions and tactile observations remains a key bottleneck. We present MILE, a teleoperation-based data-collection system comprising the human-first MILE exoskeleton and the mechanically corresponding MILE-Tac robotic hand. The system integrates custom-designed and fabricated modular joint encoders and compact MILE fingertip visuotactile sensor modules. The exoskeleton is informed by human-hand anatomy and ergonomic constraints, while the robotic hand is co-designed to preserve the selected four-finger kinematic topology. This correspondence enables joint-space command transfer and reduces reliance on task-space IK-based retargeting. The system synchronously records task-specific visual observations, four fingertip visuotactile streams, robot-hand proprioception, and exoskeleton-derived action commands. We evaluate MILE through a four-task teleoperation benchmark against representative glove-based and vision-based interfaces, and through imitation-learning experiments that compare policies trained with and without fingertip tactile input. The project page is available at https://sites.google.com/view/mile-system.
arXiv:2512.10903v2 Announce Type: replace Abstract: Circuit discovery aims to identify minimal subnetworks that are responsible for specific behaviors in large language models (LLMs). Existing approaches primarily rely on iterative edge pruning, which is computationally expensive and limited to coarse-grained units such as attention heads or MLP blocks, overlooking finer structures like individual neurons. We propose a node-level pruning framework for circuit discovery that addresses both scalability and granularity limitations. Our method introduces learnable masks across multiple levels of granularity, from entire blocks to individual neurons, within a unified optimization objective. Granularity-specific sparsity penalties guide the pruning process, allowing a comprehensive compression in a single fine-tuning run. Empirically, our approach identifies circuits that are smaller in nodes than those discovered by prior methods; moreover, we demonstrate that many neurons deemed important by coarse methods are actually irrelevant, while still maintaining task performance. Furthermore, our method has a significantly lower memory footprint, 5-10x, as it does not require keeping intermediate activations in the memory to work.
arXiv:2603.05627v2 Announce Type: replace Abstract: We introduce a notion of the ``explanation" of one (generalized) probabilistic model by another as particular kind of span in the category $\Prob$ of probabilistic models and morphisms. We show that explanations compose under a standard pullback construction (notwithstanding that $\Prob$ does not support arbitrary pullbacks). We then show that every locally-finite probabilistic model has a canonical, sharp classical explanation. The construction is functorial, so every locally-finite probabilistic theory has a canonical, sharp classical (though of course, usually non-local) representation.
arXiv:2105.13314v2 Announce Type: replace Abstract: In this article we study the continuity and sharpness of the phase transition for percolation models defined on top of planar spin systems. The two examples that we treat in detail concern the Glauber dynamics for the Ising model and a Dynamic Bootstrap process. For both of these models we prove that their phase transition is continuous and sharp, providing also quantitative estimates on the two point connectivity. The techniques that we develop in this work can be applied to a variety of different percolation models based on spin-flip dynamics. We also discuss some of the problems that can be tackled in a similar fashion.
Long-context language modeling requires not only extending context windows but maintaining coherent understanding of entity states and relationships across thousands of tokens – a challenge that semantic similarity alone cannot address. KGERMAR addresses this by constructing dynamic, context-specific knowledge graphs from input text during inference, enabling domain-adaptive retrieval that leverages both semantic similarity and explicit entity relationships. The framework performs real-time entity and relation extraction to build contextual knowledge graphs, then integrates graph-structural embeddings with textual semantics through a multi-component memory architecture. Three memory banks – contextual, semantic, and structural – are maintained with retrieval signals fused via learned weights to capture both surface-level semantics and deeper relational patterns. Evaluated on SlimPajama (84.7K training examples), WikiText-103 (4,358 examples), PG-19 (100 examples), and Proof-pile (46.3K examples), KGERMAR achieves up to 8.5\% lower perplexity and 2–2.5x better memory efficiency than memory-augmented baselines across context lengths from 1K to 32K tokens, with superior in-context learning performance across five NLU tasks. The dynamic knowledge graph construction approach advances memory-augmented language modeling by enabling domain-specific knowledge representation that adapts to input contexts rather than relying on fixed knowledge bases.
Excessive daytime sleepiness (EDS) is a common but inconsistently predicted symptom of obstructive sleep apnea (OSA). OSA is typically diagnosed with polysomnography (PSG), and the current standard for severity assessment is the apnea-hypopnea index (AHI). AHI has many limitations, including its inability to explain physiological mechanisms or reflect variability in patient symptoms, such as EDS. This retrospective study aims to find physiological and demographic parameters that better predict EDS in patients with OSA and to evaluate whether these parameters outperform AHI using PSG data from the Mount Sinai Integrative Sleep Center. Clinical variables used to predict EDS included arousal index (AI), average oxygen desaturation during sleep, average heart rate during sleep, and AHI, along with demographic variables including age, sex, and BMI. Hypothesis tests, logistic regression models, and decision tree classifier models were performed on the data to discriminate sleepy from nonsleepy patients as determined by an Epworth Sleepiness Scale (ESS) score [≥] 10. AI and oxygen desaturation were found to be the most predictive physiological variables, and sex and BMI were found to be the most predictive demographic variables. The final decision tree model with these four variables outperformed the AHI in predicting EDS. These findings suggest that daytime sleepiness in OSA can be better explained by measures of apnea burden, oxygenation impairment, and patient demographics than by AHI alone, although these remain only modestly predictive. Future studies should focus on investigating more comprehensive physiological markers, multi-night sleep data, and more objective assessments of sleepiness.
The existence and functional relevance of mitochondrial DNA methylation remain controversial. Here, we systematically profiled cytosine methylation and hydroxymethylation across human brain and blood tissues spanning healthy and malignant states using orthogonal sequencing approaches that avoid chemical conversion during library preparation. While nuclear DNA exhibited canonical methylation patterns, mitochondrial DNA consistently showed negligible signal, indistinguishable from background technical noise. By mapping cytosine-guanine sites between mitochondrial DNA and nuclear-embedded mitochondrial sequences, we demonstrate the potential of these nuclear counterparts to confound not only cytosine methylation but also hydroxymethylation measurements, corroborating and extending prior findings implicating nuclear contamination as a potential source of apparent mitochondrial epigenetic signals. Additional technical factors that inflate apparent mtDNA methylation signals were identified, including sequence context biases, flow cell chemistries, and coverage-dependent discrepancies between the heavy and light strands. Collectively, these results provide convergent evidence against the presence of biologically meaningful cytosine methylation or hydroxymethylation in mitochondrial DNA. These findings caution against interpreting apparent mtDNA methylation signals in human adult tissues as meaningful without rigorous orthogonal validation and comprehensive consideration of technical and analytical confounding factors.
arXiv:2606.14239v1 Announce Type: new Abstract: Agent skills are structured procedural packages that guide frozen LLM agents in specialized workflows. Skills rarely remain sufficient after deployment: edge cases, API changes, and deployment constraints become visible only through use, making skill evolution a practical necessity. Existing methods depend on privileged feedback such as held-out validation scores, hidden test outcomes, or environment rewards – signals often unavailable when a practitioner has only a task description and workspace data. We introduce SkillAudit, a framework for evolving agent skills without ground-truth feedback. The key idea is paired trajectory auditing: at each iteration, the same task is executed with and without the candidate skill, isolating how the skill changes agent behavior without external labels. To turn behavioral differences into edit guidance, SkillAudit uses Process-Aligned Contrastive Evaluation (PACE), a cluster of evaluators that maps trajectory divergences to diagnostic signals linked to specific passages in the skill document. A structural verifier, compiled once from the task specification and then fixed, checks task constraints and rolls back harmful updates. SkillAudit routes edits through two pipelines: Refine removes noisy or irrelevant guidance from broadly useful skills, while Repair replaces passages that conflict with the task. Across 89 containerized tasks spanning 8 professional domains, SkillAudit achieves 73.9% average task reward, outperforming an agent without skills (40.9%) and the static expert skill (56.7%). These gains are obtained without accessing hidden tests, reference solutions, or external scoring functions during evolution.
arXiv:2412.18980v2 Announce Type: replace Abstract: Uncertainty-aware deep learning (DL) models recently gained attention in fault diagnosis as a way to promote the reliable detection of faults when out-of-distribution (OOD) data arise from unseen faults (epistemic uncertainty) or the presence of noise (aleatoric uncertainty). In this paper, we present the first comprehensive comparative study of state-of-the-art uncertainty-aware DL architectures for fault diagnosis in rotating machinery, where different scenarios affected by epistemic uncertainty and different types of aleatoric uncertainty are investigated. The selected architectures include sampling by dropout, Bayesian neural networks, and deep ensembles. Moreover, to distinguish between in-distribution and OOD data in the different scenarios two uncertainty thresholds, one of which is introduced in this paper, are alternatively applied. Our empirical findings offer guidance to practitioners and researchers who have to deploy real-world uncertainty-aware fault diagnosis systems. In particular, they reveal that, in the presence of epistemic uncertainty, all DL models are capable of effectively detecting, on average, a substantial portion of OOD data across all the scenarios. However, deep ensemble models show superior performance, independently of the uncertainty threshold used for discrimination. In the presence of aleatoric uncertainty, the noise level plays an important role. Specifically, low noise levels hinder the models' ability to effectively detect OOD data. Even in this case, however, deep ensemble models exhibit a milder degradation in performance, dominating the others. These achievements, combined with their shorter inference time, make deep ensemble architectures the preferred choice.