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01.
bioRxiv (Bioinfo) 2026-06-15

RepGene: Toward a Unified Gene Representation Space Robust to Missing Biological Views

Genes can be described through multiple heterogeneous biological views, including genomic sequence, transcript sequence, protein sequence, textual knowledge, and single-cell expression context, yet existing gene embeddings remain largely modality-specific and difficult to compare or reuse when many views are unavailable. We study a narrower but practically important question: whether pretrained embeddings from these distinct sources can be organized into a shared gene representation interface that remains usable under severe missing-modality conditions. To investigate this question, we introduce RepGene, a lightweight single-branch framework that combines modality adapters, a shared encoder, presence-aware fusion, and self-supervised cross-view objectives to map five biological views into one latent space. Our goal is not to claim a new multimodal learning principle or to establish superiority over all simpler fusion strategies, but to provide an initial technical instantiation for testing whether such a shared interface is feasible in a fixed-feature setting. Under a two-stage protocol in which RepGene is trained self-supervised on frozen upstream embeddings and evaluated by downstream linear probing, we find preliminary evidence that the learned representation is broadly competitive in the full-modality setting and remains informative when only partial modality subsets are observed at inference time. The strongest signal in our study is robustness under missing views: average performance changes are often limited when one modality is removed, and even single-view inference remains non-trivial in the evaluated benchmark regime.These results do not resolve unified biological representation learning, and they should be interpreted in light of incomplete simple-fusion baselines, limited architectural ablation, benchmark dependence, and possible upstream feature exposure. We therefore position RepGene as a feasibility study and a starting point for stronger comparisons, broader benchmarks, and leakage-aware validation.

02.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

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

RepFusion: Leveraging Multimodal Priors for Denoising in Representation Space

Large language models (LLMs) are widely used in text-to-image (T2I) systems, but they are typically limited to text encoding, while denoising is handled by newly trained generative backbones. The emergence of representation autoencoders (RAEs) shifts the generation target toward semantically structured visual representations, creating a latent space that is more compatible with pretrained LLM priors. Inspired by multimodal LLMs (MLLMs), where an MLP projector is sufficient to align clean visual representations with a pretrained LLM, we repurpose the MLLM itself as a noisy representation encoder, extending this mechanism from clean to noisy inputs. We present RepFusion, which uses the resulting MLLM outputs as the conditioning signal for a diffusion transformer. In controlled comparisons at similar inference budgets, RepFusion outperforms baselines that devote comparable capacity to newly initialized denoisers. These results demonstrate that MLLMs provide strong priors for denoising visual representations and that, by conditioning on evolving noisy representations, test-time compute can be productively spent on repeated MLLM conditioning in modern T2I systems.

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

Unsupervised Causal Abstractions Discovery

arXiv:2606.19594v1 Announce Type: new Abstract: Causal abstractions formalize when a high-level structural causal model (SCM) captures the interventional behavior of a lower-level SCM. Existing applications of this notion largely follow a hypothesis-testing paradigm: an expert proposes a candidate high-level model and then evaluates if the low-level system implements it. We study the complementary problem of learning a high-level model directly from low-level measurements. Our contributions leverage hypotheses from low-rank causal discovery, and can be summarized as follows: (1) we show that observations generated by a low-rank graph induce latents that form a causal abstraction, (2) we provide identifiability results about these latents, and (3) we propose a practical objective to learn this high-level SCM.

05.
arXiv (quant-ph) 2026-06-15

Geometric mechanisms enabling spin- and enantio-sensitive observables in one photon ionization of chiral molecules

arXiv:2603.02735v3 Announce Type: replace-cross Abstract: We examine spin-resolved photoionization of randomly oriented chiral molecules via circularly polarized light, and revisit earlier predictions of Cherepkov (J. Phys. B: Atom. Mol. Phys. 16, 1543, 1983). We will show that the dynamical origin of spin- and enantio-sensitive observables arise from two intrinsic mechanisms that are quantified by two pseudovectors stemming from the geometric properties of the photoionization dipoles in spin space and in real space, and an extrinsic mechanism which is a directional bias introduced by the well-defined direction of light polarization. These mechanisms arise solely from electric dipole interactions. Consequently, this means that the ten independent parameters that was earlier predicted by Cherepkov to fully describe spin-resolved photoionization of chiral molecules can be reduced as moments of these three pseudovectors. We also find that the molecular pseudoscalars describing the spin- and enantio-sensitive components of the yield can be described by the flux of these pseudovectors through the energy shell, which changes sign upon switching enantiomers. Our results provide compact expressions for these observables which provide an intuitive picture on what determines the strength of these spin- and enantio-sensitive observables. The approach can be readily generalized to photoexcitation, multiphoton processes, and arbitrary field polarizations. Regardless of the specific driving conditions, the resulting spin- and enantio-sensitive observables are still controlled by the same three pseudovectors, underscoring their universal role as the primary generators of chirality-induced spin asymmetries, emphasizing their fundamental geometric origin and the universality of the mechanism identified here.

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

Score Approximation for Diffusion Models on Arbitrary Low-Dimensional Structures

arXiv:2606.19894v1 Announce Type: new Abstract: The remarkable success of score-based diffusion models has spurred significant efforts to establish their theoretical foundations. However, existing complexity bounds for score approximation rely heavily on restrictive assumptions like Lipschitz continuous densities or smooth manifold supports, which are routinely violated by the singularities, sharp boundaries, and disjoint clusters inherent to real-world perceptual data. This work establishes a universal score approximation theorem that works for any distribution supported on any compact set of upper Minkowski dimension $d$. Using a novel discrete-mixture formulation, we prove that the score function can be approximated with a ReLU network whose complexity grows exponentially only with $d$, thus breaking the exponential curse of ambient dimensionality. Combined with existing theories on accurately solving the backward diffusion SDE for arbitrary compact distributions, our work shows that diffusion models readily adapt to irregular, non-smooth data structures, explaining their competence in real-world generative tasks.

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

EM-NeSy: Expectation Maximization for Neurosymbolic Learning

arXiv:2606.14463v1 Announce Type: new Abstract: Neurosymbolic (NeSy) models integrate neural networks and symbolic reasoning for robust and interpretable AI. State-of-the-art NeSy models require that the symbolic component is expressed in a differentiable way, often complicating the use of approximate inference. We propose EM-NeSy which casts probabilistic NeSy learning as an instance of the Expectation-Maximization (EM) algorithm. In the expectation step, we compute the posterior over the neurally predicted symbols conditioned on the label via probabilistic inference. In the maximization step, we update the neural parameters based on this posterior using gradient descent only through the neural component. This formulation unlocks the full potential of the EM algorithm for NeSy learning. It allows NeSy to extend naturally to approximate reasoning without any additional modifications or differentiability requirements of the symbolic component. Furthermore, it recovers the standard end-to-end gradient-based NeSy setting under exact inference. Our experimental results demonstrate the scalability and computational efficiency of EM-NeSy.

08.
arXiv (quant-ph) 2026-06-16

A short proof of the modified Kretschmann-Schlingemann-Werner conjecture

作者:

arXiv:2606.16418v1 Announce Type: new Abstract: Let $\Phi_1, \Phi_2 : \mathbb{M}_d(\mathbb{C})\to \mathbb{M}_n(\mathbb{C})$ be two quantum channels with respective Stinespring isometries $V_1, V_2 : \mathbb{C}^{d}\to \mathbb{C}^{n} \otimes \mathbb{C}^{m}$ on any common dilation space $\mathbb{C}^{m}$. We prove that there exists a unitary $U$ on $\mathbb{C}^{m}$ such that $\|V_1-({\bf1}\otimes U)V_2\|_\infty\leq\sqrt{2\|\Phi_1-\Phi_2\|_\diamond},$ thus resolving vom Ende's modification of the Kretschmann-Schlingemann-Werner conjecture in the affirmative.

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

Machine learning enables roughness-driven inverse design of milling processes

arXiv:2606.16032v1 Announce Type: cross Abstract: Interest in applying data-driven approaches in manufacturing has grown significantly, particularly for mapping complex, high-dimensional relationships. The milling process is one area where predictive models can link influential parameters to surface roughness metrics prior to in situ operations. While this approach offers clear advantages, it faces challenges due to limited datasets and robustness issues in inverse design paradigms. To address these challenges, this paper proposes a machine learning (ML)-based framework for the inverse design of the surface milling process, with a focus on surface roughness as the design objective. The framework employs forward training of two ML models, a deep neural network (DNN) and a random forest (RF) ensemble, both developed using a high-fidelity synthetic dataset generated from a computational simulation framework. These trained models are integrated into a Bayesian optimization (BO) procedure to overcome the multiplicity problem arising from the many-to-one mapping inherent in the dataset. The approach identifies top-performing milling process configurations, considering both process and tool parameters, and presents them from the full solution space. The models achieve average relative errors below 5% when compared to reference results, thereby demonstrating the robustness and reliability of the proposed methodology.

10.
medRxiv (Medicine) 2026-06-12

Crimean-Congo haemorrhagic fever virus transmission: exploring perceptions of human-animal-tick interactions across six districts in Uganda

Crimean-Congo haemorrhagic fever virus (CCHFV) causes a viral zoonotic disease transmitted through tick bites and direct contact with infected blood or tissue of infected animals. Socio-ecological and behavioural risk factors for CCHFV exposure in Uganda remain poorly understood, which can lead to the omission of key risk factors in quantitative survey design and limit our wider understanding. In this study, we explored human-animal-tick interaction transmission risks in Uganda. We conducted 24 focus group discussions (FGDs) and 31 key-informant interviews (KIIs) across six environmentally and socio-ecologically diverse districts, between October 2023 and March 2024. Study sites were selected using K-prototype analysis, which combined environmental and socio-ecological variables to identify distinct clusters within Uganda. FGDs were conducted separately with groups of community leaders, men, women and teenagers with stratified purposive sampling. Medical doctors, veterinarians, traditional healers, district surveillance officers, and herdsmen were individually interviewed as key informants and purposively sampled. Data were transcribed and translated into English, and analysed thematically using iterative categorisation in NVivo 14. Most participants reported tick bites, some as frequently as every day. Close contact with animals was common, including sleeping next to them in the same building, largely due to concerns about animal theft. Less frequent but notable practices included slaughtering animals for consumption or sacrifice and interactions with wild animals during hunting. Slaughtering and butchering an animal which was sick or had died was reportedly performed by participants in most districts. Plucking and roasting engorged ticks was a practice described in the Kaabong and Arua districts of Northern Uganda. These practices and behaviours highlight potential key risks of CCHFV transmission and underscore the need for future studies to address specific behaviours, to quantify if, and to what extent, they present an exposure risk. Further work should include underlying reasons for the behaviours, which would help ensure that culturally appropriate interventions are targeted.

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

Diffusion Language Models: An Experimental Analysis

Large Language Models (LLMs) have revolutionized language modeling through autoregressive generation, enabling strong performance across a wide range of tasks. Recently, Diffusion Language Models (DLMs) have emerged as an alternative paradigm that generates text through iterative denoising rather than next-token prediction, allowing parallel refinement of entire sequences. While numerous diffusion-based architectures have been proposed, differences in evaluation protocols, datasets, inference budgets, and generation hyperparameters make it difficult to compare their capabilities and understand the trade-offs they offer. In this work, we present a systematic experimental analysis of modern DLMs. Specifically, we evaluate eight state-of-the-art DLMs across eight benchmarks spanning reasoning, coding, translation, knowledge, and structured problem solving, while explicitly considering both generation quality and computational efficiency. Beyond downstream evaluation, we analyze the impact of key inference-time factors, including denoising steps, context length, block size, and parallel unmasking strategies, and complement large-scale experiments with controlled comparisons of smaller models trained under identical conditions. Our analysis highlights the strengths and limitations of diffusion-based language modeling across different tasks, architectures, and inference budgets. We show that the behavior of DLMs is strongly influenced by generation-time design choices, leading to distinct trade-offs between performance and computational efficiency. Overall, our study provides practical insights into the capabilities and deployment characteristics of contemporary DLMs.

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

When Cognitive Graphs Meet LLMs: BDEI Cognitive Pathways for Panic Emotional Arousal Prediction

Predicting individual panic emotional arousal timing before manifestation is essential for proactive emergency intervention. Existing methods incorporate cognitive elements but none explicitly model the emotional arousal process, making them ill-suited for emotional arousal timing prediction. We argue that grounding prediction in appraisal emotion theory is necessary because it explicitly models this process, but three problems must be solved. (1) Appraisal theory posits that emotion arises from simultaneous evaluation across multiple threat dimensions, yet no prior work fuses these inputs into risk perception. (2) Existing cognitive models lack an Emotion node, decoupling threat appraisal from emotional arousal and forcing emotions to be inferred indirectly from behaviors. (3) Given their generalizable cognitive reasoning, current approaches adopt LLMs as the primary decision-maker, yet overlook the fragility and hallucination-proneness of their outputs. To address these issues, we introduce PanicCognitivePath (PCP), a framework that addresses all three. A Psychological Safety Distance (PSD) model, grounded in psychological distance theory, maps four-domain signals into a unified risk metric as the entry condition for subsequent cognitive reasoning. An explicit Emotion node grounded in appraisal emotion theory is introduced into BDI, forming a Belief-Desire-Emotion-Intention (BDEI) pathway. Agents whose risk metric exceeds the PSD threshold enter this pathway, coupling threat appraisal directly to emotional arousal. The BDEI pathway governs all state transitions while the LLM is confined to parameter estimation for the Belief-to-Desire transition, confining hallucinations to a single step and preventing error propagation. Experiments on Hurricane Sandy show PCP improves arousal timing accuracy by 10.68% over baselines, reduces peak count error to 7.07%.

13.
arXiv (CS.CV) 2026-06-19

GenTrack: A New Generation of Multi-Object Tracking

This paper introduces a novel multi-object tracking (MOT) method, dubbed GenTrack, whose main contributions include: first-a hybrid tracking approach employing both stochastic and deterministic manners to robustly handle unknown and time-varying numbers of targets, particularly in maintaining target identity (ID) consistency and managing nonlinear dynamics, second-leveraging particle swarm optimization (PSO) with some proposed fitness measures to guide stochastic particles toward their target distribution modes, enabling effective tracking even with weak and noisy object detectors, third-integration of social interactions among targets to enhance PSO-guided particles as well as improve continuous updates of both strong (matched) and weak (unmatched) tracks, thereby reducing ID switches and track loss, especially during occlusions, fourth-a GenTrack-based redefined visual MOT baseline incorporating a comprehensive state and observation model based on space consistency, appearance, detection confidence, track penalties, and social scores for systematic and efficient target updates, and five-the first ever publicly available source-code reference implementation with minimal dependencies, featuring three variants, including GenTrack Simple, Strengthen, and Super, facilitating flexible reimplementation. Experimental results have shown that GenTrack provides superior performance on standard benchmarks and real-world scenarios compared to state-of-the-art trackers, with integrated implementations of baselines for fair comparison. Potential directions for future work are also discussed. The source-code reference implementations of both the proposed method and compared-trackers are provided on GitHub: https://github.com/SDU-VelKoTek/GenTrack

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

Enabling Real-Time Point-of-Care Ultrasound Segmentation: A GPU-Free Deployment in Resource-Limited Settings

作者:

Ultrasound imaging is the most widely adopted medical modality globally due to its low cost and portability, yet artificial intelligence (AI) deployment remains constrained by reliance on GPU-accelerated models, creating a structural paradox where the cost of "intelligence" exceeds that of the imaging device itself. Here, we present the systematic adaptation and extensive evaluation of UltraSeg, an ultra-lightweight architecture originally developed for colonoscopic polyp segmentation, now engineered for point-of-care ultrasound (POCUS) across ten public datasets spanning six anatomical sites (breast, thyroid, kidney, carotid, fetal, and small-animal tumor). We systematically validate both variants in ultrasound domains: UltraSeg-130K (0.13M parameters) achieves 89.7 FPS on single-core CPUs and 34.8 FPS on a refurbished mobile device, while UltraSeg-500K (0.5M parameters) delivers 44.6 FPS on CPU and 16.1 FPS on mobile device. UltraSeg-500K matches or exceeds the Dice performance of the 31M-parameter UNet and approaches 105M-parameter TransUNet in average performance, with superior zero-shot cross-dataset generalization on external validation sets (UDIAT, DDTI). By enabling clinical-grade segmentation without GPU dependency, this work brings AI costs in line with ultrasound accessibility, making advanced diagnostics available in resource-limited settings.

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

Frame-Conditioned Moral Computation in LLaMA 3.1-8B-Instruct: A Mechanistic Interpretability Audit of Ethical Reasoning

arXiv:2606.15507v1 Announce Type: new Abstract: Behavioral audits of Large Language Models on moral prompts measure what the model says, not the internal computation producing it. We use Transluce, an AI-driven mechanistic-interpretability platform, to examine LLaMA 3.1-8B-Instruct on 54 moral prompts in four batteries: 17 dilemmas, policy, and meta-ethical questions (B1); 6 role-playing scenarios (B3); and a controlled trolley contrast varying the switching mechanism with people fixed (B4, 15 prompts) or identity attributes with mechanism fixed (B5, 16 prompts). Two complementary metric families, five cluster-level metrics and a six-metric neuron-level panel, converge on a Situational Anchor Effect: domain-specific representations dominate the top of the activation list across every battery. The model's ethics-labeled capacity stays essentially constant; its salience (rank, priority, top-of-list presence) is highly sensitive to the interpretive frame the prompt selects. The B4-vs-B5 contrast confirms the model attends to whichever surface feature varies: aggregate ethics metrics are indistinguishable, but the dominant non-ethics distractor mirrors the design. A multi-temperature audit identifies a candidate ethics neuron (L16/N3837) stable across temperatures; a cross-model behavioral proxy on two frontier models yields preliminary evidence of divergence in self-reported moral focus, consistent with an Alignment Wrapper in which RLHF re-orders surface text without removing underlying domain-first frames. We unify these as Frame-Conditioned Moral Computation: the prompt's surface vocabulary selects a feature manifold, and the moral conclusion is downstream of that selection. Behavioral alignment must be supplemented by Mechanistic Alignment: a research program asking whether ethics-related features can be shown causally privileged under controlled frame variation, not merely loud in the explanation.

17.
arXiv (CS.CL) 2026-06-19

LaViSA: A Language and Vision Structural Ambiguity Benchmark

Structural ambiguity arises when a single sentence admits multiple valid interpretations due to its syntactic structure, posing a fundamental challenge for language understanding. Visual scenes serve as useful cues for resolving such ambiguity, and Vision and Language Models (VLMs) need to be capable of deriving possible semantic interpretations from visual scenes. We introduce Language and Vision Structural Ambiguity (LaViSA), a benchmark designed to evaluate the ability of VLMs to resolve structural ambiguity leveraging visual scenes. LaViSA consists of ambiguous sentences, their disambiguated sentences, and corresponding images of these disambiguated sentences across seven ambiguity categories. Using LaViSA, we conduct a comprehensive evaluation of diverse VLMs, including both proprietary and open-source models with varying parameter scales and reasoning capabilities. Experimental results show that although recent VLMs can leverage visual scenes to resolve structural ambiguity to a some extent, they still struggle with certain ambiguity types and visually subtle semantic distinctions, indicating remaining limitations in resolving structural ambiguity using visual scenes.

18.
arXiv (CS.CV) 2026-06-12

Augmentation techniques for video surveillance in the visible and thermal spectral range

In intelligent video surveillance, cameras record image sequences during day and night. Commonly, this demands different sensors. To achieve a better performance it is not unusual to combine them. We focus on the case that a long-wave infrared camera records continuously and in addition to this, another camera records in the visible spectral range during daytime and an intelligent algorithm supervises the picked up imagery. More accurate, our task is multispectral CNN-based object detection. At first glance, images originating from the visible spectral range differ between thermal infrared ones in the presence of color and distinct texture information on the one hand and in not containing information about thermal radiation that emits from objects on the other hand. Although color can provide valuable information for classification tasks, effects such as varying illumination and specialties of different sensors still represent significant problems. Anyway, obtaining sufficient and practical thermal infrared datasets for training a deep neural network poses still a challenge. That is the reason why training with the help of data from the visible spectral range could be advantageous, particularly if the data, which has to be evaluated contains both visible and infrared data. However, there is no clear evidence of how strongly variations in thermal radiation, shape, or color information influence classification accuracy. To gain deeper insight into how Convolutional Neural Networks make decisions and what they learn from different sensor input data, we investigate the suitability and robustness of different augmentation techniques...

19.
arXiv (CS.CV) 2026-06-18

Urdu Katib Handwritten Dataset: A Historical Document Dataset for Offline Urdu Handwritten Text Recognition with CRNN-Based Baseline Evaluation

Automatic Handwritten Text Recognition (HTR) is inherently a challenging task, and its complexity is further increased when dealing with cursive scripts. Although significant efforts have been made on various cursive scripts, research regarding Urdu Handwritten Text Recognition (UHTR) has been relatively limited. This lag of research is primarily due to the unique challenges posed by its script, and the scarcity and unavailability of benchmark datasets. Therefore, to advance research in UHTR, this study presents a specialized real dataset called the Urdu Katib Handwritten Dataset (UKHD). To the best of our knowledge, this is the first offline Urdu handwritten text lines dataset specifically curated from the materials written by Katibs in historical times. It encompasses a diverse range of flat nib writing variations in the Nastalique calligraphic style. Additionally, the effectiveness of different CRNN-based hybrid models has been evaluated to identify the optimal architecture for Urdu Katib Handwriting Recognition (UKHR). Among the analyzed models, the CNN-BGRU-CTC model showed more robust performance, with low Character Error Rate (CER) and Word Error Rate (WER). This research work aims to support and encourage the research community in developing a robust recognition system for preserving Urdu handwritten literature.

20.
PLOS Medicine 2026-06-12

Comparison of count-based and clustering definitions of multimorbidity and their association with prevalence of multimorbidity, health profiles, and mortality: A cohort study of UK Biobank participants

by Gabriella C. Silva, Aurore Fayosse, Louis Jacob, Séverine Sabia, Archana Singh-Manoux, Benjamin Landré Background Multimorbidity, the presence of several chronic conditions, is linked to higher mortality and healthcare use and thus poses a major challenge for aging populations. While most studies rely on simple counts of conditions, clustering approaches have been proposed to describe patterns of co-occurring diseases. We aimed to evaluate the extent to which these methodological choices influence prevalence and association with health profiles and mortality. Methods and findings Using UK Biobank baseline data (n = 474,397), collected between 2006 and 2010, we compared six count-based definitions of multimorbidity based on different condition lists (extended, most prevalent, or body systems) and thresholds (≥2 versus ≥3 conditions). We also applied a clustering analysis to characterize subtypes of multimorbidity among participants with at least two chronic conditions. We compared prevalence and associations with concurrent health outcomes (polypharmacy, self-rated health, frailty, falls, surgery, chronic pain), blood-based measures (C-reactive protein, Cystatin-C, HDL, LDL Cholesterol, IGF-1), and 3- and 10-year mortality risks. Analyses were undertaken separately in men and women using multivariable regression models adjusted for sociodemographic characteristics and body mass index. Multimorbidity prevalence ranged from 1.0% (cluster-based) to 35.3% (count-based). Count-based definitions using lists with more conditions yielded higher prevalence. Higher thresholds identified more severe health profiles on all measured health outcomes, blood-based measures, but not higher mortality risks. Associations with blood-based measures were more pronounced using clustering, with the highest differences from the standard definition distributed across clusters. Odds ratios for 3-year mortality ranged from 1.44 [1.26; 1.64] to 4.60 [3.73; 5.62] for men and 1.35 [1.07; 1.69] to 3.83 [2.78; 5.14] for women. For 10-year mortality, they ranged from 1.42 [1.34; 1.50] to 3.86 [3.46; 4.30] in men and 1.29 [1.21; 1.39] to 3.33 [2.93; 3.77] for women, with clustering identifying groups with low prevalence and high mortality risks. Findings should be interpreted in light of the selected nature of the UK Biobank cohort and the cross-sectional assessment of several health indicators. Conclusion Operational definitions of multimorbidity substantially influence prevalence estimates, while associations with mortality appear more robust across count-based approaches. Clustering analyses provide complementary insights into heterogeneity within multimorbid populations. Future translational studies are warranted to determine how multimorbidity definitions can be optimized to ultimately improve clinical management and health outcomes in practice.

21.
medRxiv (Medicine) 2026-06-11

Long-term exposure to PM2.5 components and lipid profiles in WTC Health Program general responders

Fine particulate matter (PM2.5) was found to be associated with elevated blood lipids, but fewer studies have examined the associations with specific constituents of PM2.5. We studied the associations between exposure to annual PM2.5 and its 14 constituents, and repeated blood lipid measurements among general responders enrolled in the World Trade Center Health Program between 2003 and 2019 (n = 44,876). We used generalized additive mixed effect models to investigate the single-pollutant associations with repeated measures of blood total cholesterol (TC), high and low-density lipoprotein (HDL-C and LDL-C) levels. We then used linear generalized weighted quantile sum regression with a random intercept for participant ID to account for the clustering of repeated measures and evaluate the combined associations with the component mixture. A decile increase in the mixture of 14 PM2.5 chemical components was associated with 0.375 mg/dL increase in TC levels (95% confidence Interval (CI): 0.174-0.577) and 0.302 mg/dL increase in LDL-C (95% CI: 0.063, 0.540). Lead, organic carbon, and iron were major drivers of both associations. Component-specific models also show higher TC and LDL levels associated with interquartile range increases in organic carbon (0.472, 95% CI [0.027, 0.918] and 0.648 95% CI [0.136, 1.160]) and iron exposure (1.081, 95% CI [0.630, 1.532] and 0.748, 95% CI [0.318, 1.178]). In conclusion, we found PM2.5 exposure to be associated with elevated lipid levels. The associations differed by PM2.5 composition, highlighting organic carbon, lead, and iron and major drivers. These findings are highly significant for a population exposed to extreme air pollution event and susceptible to lipid alterations that might trigger cardiovascular events.

22.
arXiv (CS.AI) 2026-06-15

The Journal of Prompt-Engineered (Moral) Philosophy Or: Why AI-Assisted Ethics Research Requires Process Transparency

作者:

arXiv:2511.08639v4 Announce Type: replace-cross Abstract: Existing AI disclosure mandates in scholarship require that AI assistance be reported but leave transparency philosophically unspecified: they fix the duty without explaining what the duty serves. We argue that ethical inquiry is essentially contested at two independent levels – about what it is, and about what it demands of the inquirer – defeating output-only evaluation and welfare-economic dismissal of the transparency question, and, by extension, reproducibility framings imported from the empirical sciences. The transparency duty is grounded instead in agent-integrity: the legibility, before a community of inquiry, of the identity-constituting commitments that the author's mode of philosophising expresses. Because the standards for evaluating such work are not communally settled, the achievable goal for transparency is not evaluation against agreed criteria but tracking – accumulating the evidentiary record that lets each tradition assess the work on its own terms and makes future normative judgments possible. We develop a documentation-adequacy framework that operationalises Meaningful Human Control through five transparency elements – declaration, navigation, documentation account, process documentation, and development records – demonstrated by the paper itself, whose full documentation record is archived at a persistent identifier. The framework is a first iteration subject to revision, not a settled standard.

23.
arXiv (CS.LG) 2026-06-19

Optimal Coarse Correlated Equilibria in Mean Field Games: Linear Programming and No-Regret Learning

arXiv:2606.20062v1 Announce Type: cross Abstract: We introduce optimal coarse correlated equilibria for continuous-time mean field games. A coarse correlated equilibrium is a randomized recommendation scheme from which no player can gain by ignoring the recommendation and switching to an alternative strategy. The problem is as follows: a moderator selects, among all mean-field coarse correlated equilibria, one that optimizes a prescribed performance criterion, which may differ from the representative player's objective. After formulating the problem, we develop a linear programming (LP) formulation, prove the existence of optimal LP coarse correlated equilibria, and relate the LP characterization to the original probabilistic setting. Building on this characterization, we design a no-regret primal-dual algorithm, based on an equivalent Lagrangian formulation of the external-regret constraint, for learning such equilibria. We provide explicit convergence rates for the learning algorithm, and numerical examples illustrate the method.

24.
arXiv (quant-ph) 2026-06-16

Atom–photon Entanglement with a Single Trapped Cesium Atom

arXiv:2605.28968v2 Announce Type: replace Abstract: We demonstrate atom–photon entanglement using a single cesium atom trapped in an optical tweezer. Entanglement is generated by resonant excitation and subsequent spontaneous decay, which entangles the atomic Zeeman state with photon polarization. The photon is collected with a high numerical aperture objective (NA = 0.55) and coupled into a single-mode fiber, enabling atom photon measurements and measurement of the Bell-state fidelity. We obtain raw entanglement fidelity of ${\mathcal F} = 0.942(16)$ and inferred fidelity of ${\mathcal F}_inf = 0.962(26)$ after correcting independently characterized atom measurement errors. Compared with related free-space experiments using $^{87}$Rb, the multilevel structure of the relevant excited state in $^{133}$Cs requires the use of a single short excitation pulse in each entanglement attempt in order to suppress unwanted re-excitation. These results establish a free-space Cs atom–photon interface and provide a step toward dual-species Rb–Cs quantum networking.

25.
medRxiv (Medicine) 2026-06-17

Macrophage-targeted glucocorticoid prodrug resolves acute inflammation while preserving HPA axis function: mechanistic, preclinical, and Phase II/III clinical evidence

Glucocorticoids (GCs) remain the fastest-acting anti-inflammatory agents but are constrained by systemic exposure that suppresses the hypothalamic pituitary adrenal (HPA) axis, silences adaptive immunity, and drives chronic toxicities. Chronic inflammatory diseases are sustained by long-lived CD206+ macrophages containing immune-resistant pathogenic material not cleared physiologically. We developed 101-PGC-005 ('005), a macrophage-targeted type 1a dexamethasone prodrug engineered for low-affinity, recycling-compatible uptake via CD206, with intracellular release triggered by acidic endosomes. We evaluated '005 in mechanistic assays, pathogen-diverse preclinical models, three human pharmacokinetic (PK) studies, and an adaptive-design randomized Phase II/III trial in 309 hospitalized patients with moderate COVID-19. In two completed Phase I human studies, a first-in-human dose-escalation and repeated-dose study and a dedicated single/multiple-dose PK and safety study; '005 circulated as intact prodrug with rapid systemic clearance (Tmax ~0.5 h; terminal half-life ~1.9 h), with no measurable free dexamethasone after single dosing and only low, clinically non-significant free dexamethasone after repeated dosing, and intact prodrug recovered unchanged in urine. Morning cortisol and ACTH were preserved after 30 mg once daily for three consecutive days (1.5 times the intended therapeutic dose). A cerebrospinal fluid PK study is evaluating central-compartment penetration. In the Phase II/III trial, powered for non-inferiority, conducted across six sites in India under GCP with Ministry of Health approval and independent DSMB oversight; '005 (20 mg IV daily for 3 days) was superior to dexamethasone (6 mg IV daily for 3 -10 days) on the primary endpoint of time to > a 2-point improvement on the WHO ordinal scale (HR 2.31; 95% CI 1.83-2.93; p < 0.0001; median 3 vs. 4 days). '005 was also superior on viral clearance (HR 1.47; 95% CI 1.17-1.84; p = 0.0001), hospital discharge rate, SpO2; recovery, and fever resolution. Zero patients in the '005 arm received investigator-initiated corticosteroid supplementation despite protocol allowance. All 309 randomized patients completed the study (ITT = per-protocol). Safety profiles were equivalent (TEAEs 54.8% vs 54.5%; p = 0.958), with no Grade 3+ events, SAEs, deaths, or discontinuations in either arm. Mechanistically, '005 delivered dual benefit: acute debulking of inflammatory macrophages and selective depletion of chronically activated pathology-sustaining macrophages, while preserving CXCL10 antiviral signaling and physiologic HPA control. Critically, HPA preservation is not merely a safety feature, it is a core efficacy mechanism: by clearing the pathogenic macrophage burden that was overriding HPA regulation, '005 restores the conditions for endogenous cortisol to resume its pulsatile, demand-responsive anti-inflammatory role across all GR-expressing cells, lymphocytes, endothelial cells, neurons, and newly differentiated macrophages, that '005 itself cannot reach. These findings support regulatory-grade evidence for macrophage-targeted corticosteroid therapy and provide the foundation for further development across acute inflammatory indications (sepsis, viral pneumonia, cytokine-release syndromes) and chronic macrophage-driven diseases (atherosclerosis, metabolic steatohepatitis, neurodegeneration, tumor-associated macrophages).