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01.
arXiv (CS.CV) 2026-06-15

MVAD: A Benchmark Dataset for Multimodal AI-Generated Video-Audio Detection

The rapid advancement of AI-generated multimodal video-audio content has raised significant concerns regarding information security and content authenticity. Existing synthetic video datasets predominantly focus on the visual modality alone, while the few incorporating audio are largely confined to facial deepfakes–a limitation that fails to address the expanding landscape of general multimodal AI-generated content and substantially impedes the development of trustworthy detection systems. To bridge this critical gap, we introduce the Multimodal Video-Audio Dataset (MVAD), the first comprehensive dataset specifically designed for detecting AI-generated multimodal video-audio content. Our dataset exhibits three key characteristics: (1) genuine multimodality with samples generated according to three realistic video-audio forgery patterns; (2) high perceptual quality achieved through diverse state-of-the-art generative models; and (3) comprehensive diversity spanning realistic and anime visual styles, four content categories (humans, animals, objects, and scenes), and four video-audio multimodal data types. Our dataset will be available at https://github.com/HuMengXue0104/MVAD.

02.
arXiv (CS.LG) 2026-06-15

FlowMo-WM: A World Model with Object Momentum and Hidden Ambient Drift

arXiv:2606.13817v1 Announce Type: cross Abstract: World models in robot learning predict future states from visual observations and actions, enabling agents to reason about the consequences of their controls. However, many action-conditioned models are evaluated in settings where motion is dominated by immediate control, whereas aquatic surface vehicles and other real-world objects continue moving under inertia and are displaced by hidden ambient drift, such as water currents or wind. We propose FlowMo-WM, an end-to-end trainable visual world model that infers object-centric motion state and a predictive long-history context associated with hidden drift from image-action histories without direct supervision of flow fields. FlowMo-WM factorizes image-action history into a short-history latent state, trained to summarize object-centric motion, and a longer-history context, trained to summarize slowly varying exogenous influences. A zero-context residual transition separates action-conditioned base dynamics from context-dependent drift effects during latent rollout. In simulated aquatic surface-vehicle environments with diverse hidden flows, disturbances, and randomized vehicle dynamics, FlowMo-WM improves long-horizon rollout accuracy over representative action-conditioned latent world models. Prediction-time context ablations, in which the inferred context is zeroed or shuffled during rollout, show that the ambient context is important for stable prediction under hidden drift, while frozen linear probes characterize information encoded in the learned factors.

03.
arXiv (CS.CV) 2026-06-12

GeoCFNet: Geometry-Aware Confidence Field Network for Robot-Assisted Endoscopic Submucosal Dissection

Advanced surgical robotics has made robot-assisted endoscopic submucosal dissection (ESD) a promising approach for the en-bloc resection of large lesions, with the potential to reduce recurrence and improve long-term outcomes. However, the technical complexity and risk of complications in ESD demand stable and precise visual guidance to maintain an accurate dissection corridor and a safe tissue margin. Dense confidence fields provide an effective representation for this purpose by describing both the preferred dissection region and its spatial transition to surrounding tissue. However, reliable confidence field estimation remains challenging in dynamic endoscopic scenes due to smoke, specular highlights, tissue deformation, weak texture, and the thin geometric structure of the target region. To address these challenges, we formulate dissection guidance as a geometry-aware confidence field estimation problem and propose GeoCFNet, a geometry-aware confidence field network built on a pretrained DINOv3 backbone. GeoCFNet integrates a Token-Differentiated Fusion module to aggregate class-token context with dense patch representations, a SegFormer decoder for confidence regression, and Geometry-Aware Spatial Regularization (GASR) to preserve spatial coherence and local geometric transitions. Experimental results show that GeoCFNet achieves RMSE 0.0480, PSNR 27.1995, SSIM 0.3397, and CC 0.2466, indicating accurate and geometrically stable confidence field estimation for robot-assisted ESD guidance.

04.
arXiv (CS.AI) 2026-06-11

TouchThinker: Scaling Tactile Commonsense Reasoning to the Open World with Large-scale Data and Action-aware Representation

arXiv:2606.11637v1 Announce Type: new Abstract: Touch is a key modality for embodied agents to understand the physical world. Although recent work has incorporated tactile signals into language systems for tactile commonsense reasoning, scaling such systems to realistic open-world settings remains challenging due to two key bottlenecks: (1) current tactile reasoning datasets remain limited in format and scale, providing insufficient supervision for reasoning from tactile observations to physical commonsense and hindering the learning of transferable tactile commonsense; (2) Tactile signals are inherently redundant and action-specific, yet existing methods often overlook these properties, resulting in inefficient representations with limited semantic expressiveness. To address these limitations, we propose TouchThinker, a tactile-language framework that scales tactile commonsense reasoning to the open world from both data and representation perspectives. First, we construct TouchThinker-1M, a million-scale, multi-source tactile reasoning dataset covering 415 objects, 8 scenarios, and 7 sensor types, providing a solid data foundation for open-world generalization. We further introduce TouchThinker-Bench, an open-world benchmark with more realistic and diverse tasks. Then, we propose action-aware modeling mechanism to improve tactile representation efficiency and enable efficient reasoning. Experimental results demonstrate that TouchThinker achieves competitive performance against state-of-the-art models across multiple datasets. Our code and dataset will be made available at: https://github.com/lvkailin0118/TouchThinker.

05.
bioRxiv (Bioinfo) 2026-06-18

Looking beyond stereotyped neuron structures reveals links between beading and morphological rearrangements in aging phenotypes.

Understanding how neuronal morphology changes during aging and acute stress is essential for elucidating mechanisms of neurodegeneration. The highly branched PVD neuron of Caenorhabditis elegans provides a powerful model for studying dendritic remodeling and degeneration-associated phenotypes such as dendritic beading. However, the complexity of this arbor presents substantial challenges for automated segmentation and quantitative analysis. In this study, we adapted a convolutional neural network (CNN)-guided region growing framework for automated dendrite tracing, coupled with two topology-based algorithms for categorizing dendritic segments by branching degree. The segmentation algorithm achieved high accuracy relative to manual tracing, with a median Dice coefficient of 0.82, while reducing analysis time by approximately tenfold. Automated dendrite categorization demonstrated strong agreement with manual annotations across branching orders, though position-based mapping performance declined with age due to progressive morphological distortion. Leveraging this platform, we investigated mechanistic differences in dendritic beading patterns observed during aging and cold shock. Consistent with prior work, aging was associated with decreased inter-bead spacing, whereas cold shock produced increased bead dispersion with stress severity. Structural analysis revealed that these trends were not driven by dendritic pruning or reduced arbor complexity. Instead, while a traditional anatomically unflexible paradigm falsely implicated lower-degree dendrites as highly vulnerable, our branching-informed framework revealed that age-dependent beading is fundamentally dictated by a segments history of successive branching events. Conversely, acute cold shock triggered systemic beading that expanded across all dendritic orders in a severity-dependent manner. Together, these findings demonstrate that chronic aging and acute stress engage distinct degenerative pathways (compartment-specific lineage vulnerability versus global architectural collapse) rather than gross morphological loss, as well as highlighting the need for paradigms that enable reliable analysis of changing morphologies.

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

Your Mouse and Eyes Secretly Leak Your Preference: LLM Alignment using Implicit Feedback from Users

To align a Large Language Model (LLM), most existing methods collect explicit human feedback and train a reward model to predict the human preference based on the response text. These existing methods have two key limitations. First, the users rarely provide explicit feedback for LLM responses, which makes the high-quality preference annotation expensive to collect. Second, the methods do not leverage implicit human feedback, which has proven vital to the economic moats of Internet giants. To quantify the value of implicit feedback, we build a new dataset called IFLLM, which collects 1336 multi-turn questions from the 59 Mechanical Turk workers, their mouse trajectories, and eye gazing points to the LLMs' responses from their webcams. IFLLM shows that the users have very diverse types of gazing behavior and mouse trajectories. Our reward model based on the implicit user feedback boosts the accuracy of the text-based reward model from 55% to 64% and nearly triples the relative response quality improvements after applying the DPO to eight LLMs, demonstrating the value of implicit feedback in the wild. Our data collection website, dataset, and codes can be found at https://github.com/themehulpatwari/llm-implicit-feedback/.

07.
arXiv (CS.CL) 2026-06-18

GrowthHacker: Automated Off-Policy Evaluation Optimization Using Code-Modifying LLM Agents

With data-driven development now widely adopted, online A/B testing is an established method for measuring the effects of new technologies. However, deploying online experiments demands resources for design, implementation, and deployment, and may negatively impact users (e.g., unsafe or unethical outcomes) while requiring weeks of data collection. To address this, the growing research area of off-policy evaluation (OPE), or offline A/B testing, assesses new technologies offline using previously collected logged data. OPE is also a fundamental problem in reinforcement learning and is important where online testing is expensive or risky, such as healthcare, recommender systems, education, and robotics. Despite advances in code-generation large language models (LLMs) and agentic workflows, little is known about whether and how LLMs and LLM-based agents can automatically optimize OPE implementations. We propose GrowthHacker, a benchmark that evaluates baseline LLMs and LLM-based agents on large-scale public datasets. GrowthHacker autonomously and iteratively modifies code, runs OPE, and uses the metrics to guide subsequent optimization. We evaluate methods on Open Bandit Pipeline (OBP) and Scope-RL, and develop a two_agent framework that addresses limitations of existing frameworks while reducing complexity. Across both libraries, two_agent shows the highest reliability (98.1%-100% success rate) and positive-outcome rate (78%), with a median improvement of 4.4% among positive outcomes; CrewAI achieves the highest average improvement (37.9%) and is the only framework with zero extreme-value failures. AutoGen and Default each reach 65% positive-outcome rates. These results establish the feasibility of using LLM-based agents as automated "growth hackers" to continuously improve OPE systems, with implications for scaling data-driven decision-making where manual optimization is expensive.

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

Rotational Symmetry based Object Pose Estimation from Point Clouds in the Absence of Known 3D Models

Object pose estimation is crucial to many industrial applications, with one example being automated spray painting using a robot. However, confidentiality concerns often limit access to high-quality 3D models, posing a significant challenge for point-cloud-based pose estimation. In such scenarios, rotational symmetry, a readily accessible characteristic of many industrial objects, can provide valuable prior information to facilitate pose estimation.In this paper, we propose a method that leverages the rotational symmetry commonly found in industrial objects to address the challenge caused by the absence of 3D models. The object pose is jointly estimated with point cloud refinement through an iterative optimization process. This optimization relies on a rotational symmetry constraint loss. To construct this loss, each 3D point is rotated according to the currently estimated pose, and multiple correspondences are identified using nearest-neighbor search by exploiting the rotational symmetry property. These correspondences are then used to compute the rotational symmetry constraint loss, which iteratively refines both the pose and the point cloud.By explicitly incorporating rotational symmetry into the optimization process, the proposed method achieves robust pose estimation and generalizes well across diverse object types. The proposed method is evaluated on a dataset specifically created for point clouds without known 3D models, consisting of four categories of synthetic objects and one real wheel hub collected from a production line. Experimental results demonstrate that the proposed method achieves performance comparable to methods that rely on known 3D models.

09.
arXiv (CS.AI) 2026-06-11

Offline Diffusion Policy for Multi-User Delay-Constrained Scheduling

arXiv:2501.12942v2 Announce Type: replace Abstract: Effective multi-user delay-constrained scheduling is crucial in various real-world applications, including embodied AI, instant messaging, live streaming, and data center management, where efficient resource allocation is required among users with diverse delay sensitivities. In these scenarios, schedulers must make real-time decisions to satisfy both delay and resource constraints without prior knowledge of system dynamics, which are often time-varying and challenging to estimate. {Current learning-based methods typically require online interactions with actual systems during the training stage. Therefore, these approaches are often difficult or impractical, as they can significantly degrade system performance and incur substantial service costs.} To address these challenges, we propose a novel offline reinforcement learning-based algorithm, named \underline{S}cheduling By \underline{O}ffline Learning with \underline{C}ritic Guidance and \underline{D}iffusion Model (SOCD), to learn efficient scheduling policies purely from pre-collected offline data. SOCD innovatively employs a diffusion policy, complemented by a sampling-free critic network for policy guidance. By integrating the Lagrangian multiplier optimization into the offline reinforcement learning, SOCD efficiently trains high-quality constraint-aware policies exclusively from available datasets, eliminating the need for online interactions with the system. Experimental results demonstrate that SOCD is resilient to various system dynamics, including partially observable and large-scale environments, and delivers superior performance compared to existing methods.

10.
arXiv (CS.AI) 2026-06-17

A Neuro-Symbolic Approach to Strategy Synthesis for Strategic Logics

arXiv:2606.17962v1 Announce Type: cross Abstract: Reasoning about what agents can achieve through strategic interaction is a core challenge in Multi-Agent Systems (MAS). Logics for strategic ability, such as ATL, provide rigorous methods, but their adoption is often hindered by the computational cost of strategy synthesis. We introduce a neuro-symbolic framework that integrates large language models (LLMs) into the model-checking pipeline for MAS. The LLM acts as a strategy-generation oracle, proposing candidate strategies that are then formally validated by a standard MAS model checker. This generate-and-certify architecture uses LLM guidance to navigate large combinatorial strategy spaces while preserving formal soundness: generated strategies are accepted only when certified by the verifier. We instantiate the framework for bounded strategic reasoning in NatATL and introduce the first NatATL strategy-synthesis dataset, consisting of 4211 instances. Experiments with an open-weight Qwen3-32B model show that our certified pipeline achieves 92\% accuracy on strategy-synthesis outcomes.

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

Which Models Are Our Models Built On? Auditing Invisible Dependencies in Modern LLMs

Modern LLM training pipelines increasingly rely on other models to generate data, filter corpora, judge outputs, and guide development decisions. These dependencies are recursive: a model may depend on an upstream artifact whose own dependencies are documented only in separate releases and artifacts. As a result, the full dependency structure is fragmented across heterogeneous public artifacts, with complexity and recursive depth far outpacing humans' ability to trace. We introduce ModSleuth, an agentic system that recursively reconstructs LLM dependency graphs from public artifacts with source-grounded evidence. We find that the primary challenge is no longer information extraction, but defining what constitutes a dependency and reconciling artifact references across inconsistent documentation. We address these challenges through a formalization that distinguishes direct and indirect dependencies, represents heterogeneous pipeline roles through operation-centered relationships, and resolves artifact identities across names, versions, and repositories. Applying ModSleuth to four public-artifact-rich LLM releases, we recover 1,060 source-verified dependencies and construct large-scale dependency graphs of modern LLM development. These graphs reveal multi-hop license obligations, train-evaluation coupling, discrepancies between released and training-time artifacts, and documentation inconsistencies that would otherwise be difficult to uncover. We release ModSleuth and the resulting dependency graphs to support transparent analysis of the increasingly complex ecosystems underlying modern LLMs.

12.
arXiv (CS.CV) 2026-06-11

TextHOI-3D: Text-to-3D Hand-Object Interaction via Discrete Multi-View Generation and Joint Mesh Optimization

Text-conditioned 3D generation has progressed rapidly for images and isolated objects, but producing a hand-object mesh remains challenging: the output must preserve language semantics, cross-view consistency, object geometry, articulated hand shape, and physically plausible contact. We present TextHOI-3D, a staged framework that uses generated multi-view observations as an explicit interface between text-conditioned visual generation and geometry-aware hand-object recovery. TextHOI-3D learns a compact VQ token space for fixed-camera hand-object observations, predicts multi-view visual tokens from text with a CLIP-conditioned visual autoregressive model, and recovers a unified hand-object mesh through prior initialization, multi-view joint optimization, and anti-penetration refinement. The design separates semantic generation from geometric recovery while keeping both stages connected by a discrete multi-view representation. On HO3D-derived evaluations, the multi-view setting reduces object CD from 17.26 mm to 4.92 mm and penetration volume from 5.3721 cm^3 to 0.2193 cm^3 compared with a single-view counterpart, while improving hand errors and surface F-scores. These results support multi-view visual tokens as an effective intermediate representation for text-driven 3D hand-object mesh creation.

14.
arXiv (CS.CV) 2026-06-18

Characterizing Brazilian Atlantic Forest Restoration Outcomes with Geospatial AlphaEarth Embeddings

Authors:

The Atlantic Forest in Brazil is a critical biodiversity hotspot, yet less than 12-15% of its original cover remains. Although monitoring forest restoration on a large scale is essential, traditional methods are limited by the impracticality of on-the-ground reporting on such a scale and by the saturation of remote-sensing indices such as NDVI. Furthermore, reforestation is a gradual process as opposed to the rapid spectral changes caused by deforestation. In this study, we examine 1,729 restoration sites in S\~ao Paulo, using satellite embeddings from the AlphaEarth Foundation's model to evaluate their effectiveness in characterising early restoration success. We introduce the concept of a 'Reference Trajectory Embedding', defining a metric of restoration success based on cosine similarity to reference sites of mature secondary forest. We observe distinct clusters in embedding space according to different land use and land cover (LULC) types, and we can identify sites with clear change vectors. However, the signal can be noisy, and embeddings may require further fine-tuning to capture and predict site metadata beyond LULC.

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

Towards Effective Waste Segmentation for Automated Waste Recycling in Cluttered Background

Rapid expansion of urban areas and population growth is causing an immense increase in waste production, which demands the need for efficient and automated waste management. In this scenario, automated waste recycling (AWR) using deep learning methods can assist humans in optimal waste management. Recent deep learning approaches for AWR provide promising waste segmentation performance, however, these methods rely on large backbone networks that are inefficient for AWR systems and suffer from performance deterioration in cluttered scenes. To this end, an optimal waste segmentation network is introduced which effectively utilizes the spatial domain to capture localized structural dependencies and the spectral domain to efficiently extract global contextual relationships. This cascaded design allows the network to progressively leverage both local and global representations across complementary domains to highlight the semantic information necessary for effective segmentation of various waste objects. Furthermore, auxiliary feature enhancement module (AFEM) is introduced to enhance the target objects' boundaries and blob amplification for better segmentation in cluttered scenarios. Extensive experimentation on ZeroWaste-aug, ZeroWaste-f and SpectralWaste datasets reveals the merits of the proposed method.

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

The Measurement Gap in the Automation of EU Law: Benchmarking Doctrinal Legal Reasoning under the EU AI Act

Large language models now produce legal text of at least median quality, yet no existing benchmark can evaluate whether they perform doctrinal legal reasoning, which forms the interpretive core of legal work, rather than the ancillary, paralegal tasks that most current legal-AI evaluations measure. This measurement gap is not only methodological but legal: the EU AI Act makes "appropriate accuracy" a binding requirement for high-risk AI used in the judicial domain, yet that requirement cannot acquire operational content without the very doctrinal-reasoning benchmark the field lacks.

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

Identifying Structural Biases from Causal Mechanism Shifts

arXiv:2606.18834v1 Announce Type: new Abstract: Causal discovery methods commonly assume that all data is independently and identically distributed (i.i.d.) and that there are no unmeasured variables affecting the system. In practice, these assumptions are often violated, leading to inaccurate inference. In this paper, we study how to identify hidden confounding and selection biases from causal mechanism shifts. In particular, we show that structural biases lead to dependent mechanism shifts. That is, by considering for which variables the mechanisms change given data from different environments, we can tell which variables are unbiased, which are subject to hidden confounding, and which are undergoing selection bias. We formalize this into an empirically testable criterion based on mutual information, and show under which conditions it identifies structural biases. To tell which nodes are subject to what kind of bias, we introduce the StruBI algorithm. Experiments on synthetic and real-world data show that StruBI works well in practice, accurately recovering affected variable sets and types of biases, outperforming the state-of-the-art by a wide margin.

19.
arXiv (quant-ph) 2026-06-19

Entanglement structure of the dynamical phases in the sub-Ohmic spin-boson model

arXiv:2606.20313v1 Announce Type: new Abstract: The sub-Ohmic spin-boson model exhibits three distinct dynamical regimes in its spin population dynamics, classified as coherent, incoherent, and pseudo-coherent. Whether these regimes correspond to distinct spin-bath entanglement structures remains an open question. Here we address this using tree tensor network states with projector-splitting time evolution (TTN-TDVP-PS), scanning a broad grid in the sub-Ohmic $(s, \alpha)$ plane. We find that the spin entanglement entropy $S_\mathrm{spin}(t)$ reaches a stationary plateau on a timescale shorter than the polarization relaxation, enabling construction of a stationary entropy landscape from the stationary value $S_\mathrm{stable}$. Within this scalar entropy landscape, the entropy ridge broadly follows the population-based phase boundary at small $s$, but does not reproduce the two-branch structure at large $s$. The ridge remains single-valued within the incoherent region rather than separately tracking both population-based transitions. The Bloch-sphere representation provides a geometric interpretation of this behavior. The entropy plateau corresponds to trajectories settling onto constant-radius shells, with the ridge marking the parameters of smallest stationary Bloch radius. Mode-resolved bath entanglement shows that low-frequency modes dominate the environmental entropy scale and that coherent dynamics enhance bath-mode correlations beyond direct spin–mode correlations. These results establish the stationary spin entanglement entropy as a physically informative observable that complements population-based classifications of dissipative quantum dynamics.

20.
arXiv (CS.CV) 2026-06-12

Navigating Gigapixel Pathology Images with Large Multimodal Models

Recent advances in large multimodal models have allowed for the development of interactive chat models that can converse and reason about pathology whole-slide images (WSIs). However, existing slide-level chat systems are often highly specialized, typically compressing WSIs into fixed slide-level embeddings or relying on multi-component pipelines, which can lose multi-scale detail and limit generalizability beyond the target task. We present GIANT (Gigapixel Image Agent for Navigating Tissue), a simple, training-free approach that lets general-purpose multimodal models navigate WSIs on their own, iteratively selecting multi-magnification crops and aggregating evidence over time. To evaluate generalizability in WSI question answering and to promote reproducibility, we introduce MultiPathQA, a benchmark suite spanning five clinical challenges and 934 questions over 868 unique WSIs. This includes a new set of 128 pathologist-authored multiple-choice questions designed to mirror real diagnostic search and multi-scale reasoning. Using GPT-5, GIANT outperforms models specialized for pathology question answering, achieving state-of-the-art performance on four out of five benchmarks.

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

Learning Visually Interpretable Oscillator Networks for Soft Continuum Robots from Video

Learning soft continuum robot (SCR) dynamics from video offers flexibility but existing methods lack interpretability or rely on prior assumptions. Model-based approaches require prior knowledge and manual design. We bridge this gap by introducing: (1) The Attention Broadcast Decoder (ABCD), a plug-and-play module for autoencoder-based latent dynamics learning that generates pixel-accurate attention maps localizing each latent dimension's contribution while filtering static backgrounds, enabling visual interpretability via spatially grounded latents and on-image overlays. (2) Visual Oscillator Networks (VONs), a 2D latent oscillator network coupled to ABCD attention maps for on-image visualization of learned masses, coupling stiffness, and forces, thereby enabling mechanical interpretability. We validate our approach on single- and double-segment SCRs, demonstrating that ABCD-based models significantly improve multi-step prediction accuracy with 5.8x error reduction for Koopman operators and 3.5x for oscillator networks on a two-segment robot. VONs autonomously discover a chain structure of oscillators. This fully data-driven approach yields compact, mechanically interpretable models with potential relevance for future control applications.

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

DuDi: Dual-Signal Distillation with Cross-Lingual Verbalizer

Small language models (SLMs) are efficient and scalable, but their multilingual capabilities degrade severely at sub-billion scales, especially for Southeast Asian (SEA) languages. We introduce DuDi, a dual-signal multilingual distillation framework that combines an online sequence-level signal with off-policy and on-policy token-level signals. DuDi further uses a cross-lingual verbalizer to refine teacher feedback and improve teacher-student transferability in multilingual settings. Experiments on SEA-HELM across multiple model families, scales, and teacher-student settings show that DuDi consistently outperforms competitive distillation baselines. Ablations and analyses confirm that sequence-level optimization, token-level supervision, and cross-lingual verbalization provide complementary and transferable learning signals for multilingual SLMs.

23.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Authors:

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.

24.
PLOS Computational Biology 2026-06-03

IsoPepTracker: An interactive web application for peptide-driven isoform analysis

Authors:

by Araf Mahmud, Chen Huang Alternative splicing affects 95% of multi-exon genes, generating protein isoforms with distinct functions. While current alternative splicing analyses effectively identify splice events at the RNA level, they provide limited protein-level insight. To address this gap, we developed IsoPepTracker (https://www.isopeptracker.org), a user-friendly web application for analyzing and visualizing differential peptides across canonical and novel isoforms that are theoretically detectable by shotgun mass spectrometry-based proteomics. IsoPepTracker features four modules: Canonical Isoform Analysis, Novel Isoform Discovery, Peptide Sequence Search, and Alternative Splicing Analysis. Each module is tailored for distinct and complementary proteogenomics analyses. Users can input genes, novel cDNA sequences, peptides, or alternative splicing results to pinpoint peptides of interest and identify their associations with target genes or isoforms. We demonstrate the straightforward application of IsoPepTracker in proteogenomics through case studies. IsoPepTracker not only provides informative peptide signatures to understand the protein-level consequences of alternative splicing but also supplies peptide candidates for validation in shotgun proteomics.

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

Multi-Class Brain Tumor Classification Using Advanced Deep Learning Models: A Comparative Study

Despite recent advancements in deep learning, accurately classifying brain tumors from MRI images continues to pose challenges. In this research, we present a comprehensive evaluation of five different convolutional neural networks (CNN) architectures, including a customized baseline model and four pre-trained models - for use in classifying multi-class brain tumors using a clinically-sourced dataset of approximately 10,000 MRI images. We have utilized five different architectures; VGG16, VGG19, DenseNet121, and EfficientNetB0, which were all tested and trained within an identical experimental framework. Performance was measured by both overall accuracy and tumor-wise recall as a means to measure the clinically-relevant performance of each architecture. We found that EfficientNetB0 had the best overall classification accuracy at 95%, when compared to the other architectures tested; specifically VGG16 (94.37%), VGG19 (92.29%), DenseNet121 (90.91%) and the customized CNN (78.00%). An especially important finding of our research was the considerable improvement in detecting meningiomas; specifically, while simple CNNs could detect meningiomas with a recall rate of approximately 20%, EfficientNetB0 was able to detect meningiomas with a recall rate of 89%. Meningiomas are often difficult to detect because they can appear very subtly on MRI images. Additionally, an interesting finding was that the deeper VGG19 performed worse than the shallower VGG16. This indicates that in many cases the architectural efficiency of a CNN model may be more important than its depth when working with medical images. Overall, EfficientNetB0 appears to provide the optimal trade-off between classification accuracy, number of parameters used in the model and clinically meaningful performance.