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01.
arXiv (CS.AI) 2026-06-17

Feynman Kac Reweighted Schrödinger Bridge Matching for Surface-Based Tau PET Harmonization

arXiv:2606.17420v1 Announce Type: cross Abstract: Tau PET imaging is central to tracking Alzheimer's disease progression, but systematic differences between scanners, protocols, and radiotracers across sites introduce nonbiological variability that inflates biomarker variance, reduces sensitivity to disease effects, and can bias downstream clinical assessments. Harmonization methods aim to remove these site-induced shifts while preserving biologically meaningful signal, yet existing approaches struggle when source and target cohorts differ in subgroup composition, risking conflation of site effects with biological variation such as tau-positivity status. We propose the Feynman Kac Reweighted Schröodinger Bridge Matching (FKRSBM) model to address this problem. Rather than routing data through a Gaussian noise prior as in diffusion-based methods, FKRSBM learns a direct stochastic transport process between source and target distributions via entropy-regularized optimal transport. To enforce biologically consistent transport, FKRSBM incorporates a subgroup-aware endpoint proposal derived from a Feynman Kac reweighting of the reference bridge measure, implemented entirely through stratified importance sampling at the data level and requiring no changes to the underlying bridge-matching solver or network architecture. For surface-based neuroimaging, FKRSBM employs a spherical convolutional backbone operating on cortical meshes to perform vertex-level harmonization. We evaluate the method on tau PET SUVR maps, harmonizing PI-2620 data from the HABS-HD cohort into the AV-1451 domain of ADNI. Compared against ComBat, CycleGAN, a diffusion-based method (DF), and unregularized Diffusion Schröodinger Bridge Matching (DSBM), FKRSBM achieves superior distributional alignment, reduced tau-positivity sign mismatch, stronger APOE subgroup alignment, and improved downstream disease classification performance.

02.
arXiv (CS.CV) 2026-06-11

XPR: An Extensible Cross-Platform Point-Based Differentiable Renderer

Point-based differentiable rendering underpins modern 3D reconstruction, novel-view synthesis, and learning-based graphics pipelines, but developing new rendering methods often requires extensive low-level implementation, hardware-specific kernels, and manually written backward passes. This limits rapid prototyping, reproducibility, exploration, and deployment, especially across diverse hardware platforms. This paper presents XPR, an extensible cross-platform framework for point-based differentiable rendering. XPR introduces a high-level programming interface that separates method-specific logic from the shared rendering pipeline, allowing users to implement new methods in a few lines of code. Its pipeline decomposes rendering into modular, statically shaped parallel operations that can be lowered by a cross-platform compiler to GPUs, TPUs, CPUs, and other ML accelerators. We demonstrate implementations of 3DGS, 3DGUT, and LinPrim, with only a few 100s lines of Python code, each of which can be compiled to a range of hardware platforms with the XLA compiler. These results show that XPR enables fast experimentation and portable execution for emerging point-based differentiable rendering systems.

03.
arXiv (CS.CV) 2026-06-19

Can Agents Distinguish Visually Hard-to-Separate Diseases in a Zero-Shot Setting? A Pilot Study

The rapid progress of multimodal large language models (MLLMs) has led to increasing interest in agent-based systems. While most prior work in medical imaging concentrates on automating routine clinical workflows, we study an underexplored yet clinically significant setting: distinguishing visually hard-to-separate diseases in a zero-shot setting. We benchmark representative agents on two imaging-only proxy diagnostic tasks, (1) melanoma vs. atypical nevus and (2) pulmonary edema vs. pneumonia, where visual features are highly confounded despite substantial differences in clinical management. We introduce a multi-agent framework based on contrastive adjudication. Experimental results show improved diagnostic performance (an 11-percentage-point gain in accuracy on dermoscopy data) and reduced unsupported claims on qualitative samples, although overall performance remains insufficient for clinical deployment. We acknowledge the inherent uncertainty in human annotations and the absence of clinical context, which further limit the translation to real-world settings. Within this controlled setting, this pilot study provides preliminary insights into zero-shot agent performance in visually confounded scenarios.

04.
medRxiv (Medicine) 2026-06-12

Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive molecular complexity, profound stromal remodeling, and limited responsiveness to systemic therapies. Although gemcitabine-based regimens remain widely utilized, the molecular pathways that influence treatment-associated biological variation are incompletely understood. The TGF{beta} and JAK/STAT signaling networks are recognized regulators of tumor progression, immune modulation, and therapeutic resistance; however, their genomic architecture in clinically stratified PDAC populations remains poorly defined. Methods: We employed a conversational artificial intelligence-driven analytical framework to investigate TGF{beta} and JAK/STAT pathway alterations in a cohort of 184 PDAC patients. Clinical and molecular data were integrated to generate age- and treatment-stratified cohorts, enabling pathway-level and gene-level analyses according to gemcitabine exposure. Findings generated through AI-assisted interrogation were subsequently evaluated using conventional statistical approaches. Results: TGF{beta} pathway alterations were identified in approximately one-quarter to one-third of tumors across clinical subgroups and demonstrated relatively stable frequencies regardless of age at diagnosis or gemcitabine treatment status. Gene-level analyses revealed that pathway disruption was predominantly driven by recurrent alterations in SMAD4, with additional low-frequency events involving TGFBR1 and TGFBR2. Notably, TGFBR2 mutations were significantly more frequent among late-onset PDAC patients receiving gemcitabine compared with untreated late-onset patients (8.8% vs. 1.4%; p = 0.04), suggesting a potential treatment-associated enrichment. In contrast, JAK/STAT pathway alterations were rare throughout the cohort, with only isolated mutations observed in pathway components including JAK1, JAK2, JAK3, STAT1, STAT3, and related regulatory genes. No significant differences in JAK/STAT alteration frequencies were identified according to age or treatment exposure. Conclusions: TGF{beta} and JAK/STAT pathways exhibit distinct genomic architectures in PDAC. TGF{beta} pathway disruption represents a recurrent feature of disease biology, largely driven by SMAD4 alterations, while TGFBR2 enrichment in gemcitabine-treated late-onset tumors suggests a potential context-specific association worthy of further investigation. Conversely, genomic alterations within the JAK/STAT pathway are uncommon, indicating that pathway activity may be regulated predominantly through non-genomic mechanisms. These findings demonstrate the utility of conversational artificial intelligence agents for rapid, scalable, and clinically contextualized pathway interrogation and support future studies integrating multi-omic data to refine precision medicine strategies in PDAC.

05.
arXiv (CS.CV) 2026-06-16

Revealing Artifacts via Noise Amplification: A Novel Perspective for AI-Generated Video Detection

With the rapid advancement of video generation models, distinguishing between AI-generated and authentic videos has emerged as a challenging endeavor. The majority of existing research endeavors concentrate on the development of detectors for identifying samples generated by generative adversarial networks. Nevertheless, the detection of AI-generated videos, particularly those produced by text-to-video models, still remains an uncharted territory. Although state-of-the-art text-to-video models can generate realistic visual content similar to real videos, they fall short of generating the details of the images and the changes in details within the videos. Inspired by this, we address AI-generated video detection from a novel perspective of bit-planes, which can effectively describe the details or noises in images or videos. To this end, we propose a simple yet effective approach called Noise Amplification. This approach first extracts noise signals based on bit-planes, then amplifies these noise signals, and finally feeds them into the discriminator networks for video fake classification. Noise amplification is comprehensively constructed by incorporating three aspects: pixel-level intensity enhancement, region-level spatial amplification, and frame-level temporal aggregation. To evaluate methods of AI-generated video detection in challenging scenarios, we also introduce a benchmark named HardGVD. Extensive experiments on both the large-scale dataset GenVidBench and HardGVD show that our simple approach significantly outperforms state-of-the-art methods.

06.
PLOS Computational Biology 2026-06-05

Heuristic multi-site optimization for protein sequence design using Masked Protein Language Models

Authors:

by Lijuan Wang, Yuze Wang, Chen Qiu, Liwei Xiao, Xianliang Liu, Junjie Chen Protein sequence design for tailored functional properties is a fundamental task in protein engineering, with critical applications in drug discovery and therapeutic development. Efficient navigation of the combinatorial vastness of protein sequence space to identify functional variants remains a formidable challenge. Conventional approaches, which predominantly rely on template-based local search or single-residue mutagenesis, are constrained by their susceptibility to local optima and their potential risk of destabilizing native structural stability. In this study, we introduce ProtHMSO, a heuristic multi-site optimization framework leveraging masked protein language models (ProtLMs) for context-aware sequence exploration. ProtHMSO mimics natural evolutionary mechanisms by employing ProtLM-derived substitution probabilities to guide heuristic searches for synergistic mutations, thereby constraining combinatorial search spaces through evolutionary and biophysical priors. ProtHMSO is further applied to replace the exploration strategies in genetic algorithms (GAs) and Monte Carlo tree search (MCTS) for improving their convergence efficiency. Benchmark experiments demonstrate that protein sequences generated by ProtHMSO exhibit superior functional performance and closer alignment with natural sequence distribution, compared with state-of-the-art methods. These advancements highlight that ProtHMSO has strong potential and compatibility to accelerate functional protein discovery, offering a robust framework for efficient and context-aware exploration of protein sequence space.

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

HandwritingAgent: Language-Driven Handwriting Synthesis in Scalable Vector Space

Teaching machines to emulate natural handwriting styles remains an open challenge, as it requires synthesizing stroke sequences that dynamically vary in shape, texture, pressure and script - not only across individuals, but also within a single person's handwriting. Attempts at this challenge have largely explored deep learning methods in both online and offline settings. However, these approaches are often constrained by style-specific architectural choices, heavy reliance on large datasets, high compute costs, and a lack of flexible control over writing styles through natural language. To this end, we introduce HandwritingAgent, a language-driven agent that can synthesize natural handwriting sequences directly in Scalable Vector Graphics (SVG) format with no need for style-specific training. The agent leverages a large reasoning model to geometrically analyse and autoregressively generate target handwritten glyphs as stroke sequences in a discrete grid canvas environment. Generation is conditioned on texts provided in either conversational or non-conversational mode, along with a reference handwriting-style image. Experiments on diverse handwriting tasks spanning imitation, recognition, multi-lingual handwriting synthesis, and generation of complex handwritten maths and science expressions indicate substantial improvement in performance, with HandwritingAgent matching or surpassing state-of-the-art generative handwriting models, while providing a more efficient, controllable, and generalizable synthesis method.

08.
arXiv (math.PR) 2026-06-19

Extremal representations of functions of matrices and applications to multivariate prediction

arXiv:2606.19359v1 Announce Type: cross Abstract: Motivated by two seminal results of multivariate prediction theory by Helson and Lowdenslager and by Wiener and Masani we prove extremal representations of functions of matrices and derive their prediction-theoretic consequences. We also sketch a way to obtain matricial inequalities from our results. The main goal of the paper is the computation of the infimum of a set of values of the form $tr(A \Delta A^*)$, where $\Delta$ is a given non-negative Hermitian $n \times n$ matrix and the choices for $A$ exhauste a certain set of $n \times n$ matrices. In particular, we focus on norm-bounded unit spheres with certain types of properties of unitary invariance, what allows an application of the theory of majorization.

09.
arXiv (CS.CV) 2026-06-15

Rotation-Invariant Spherical Watermarking via Third-Order SO(3) Representation Coupling

Reliable watermarking of panoramic imagery is fundamentally challenged by arbitrary 3D rotations. As panoramas are defined on the sphere, they naturally transform under the action of $SO(3)$, rendering conventional planar representations and augmentation-based robustness strategies inadequate and devoid of theoretical guarantees. To address this, we formulate panoramas as spherical signals and leverage $SO(3)$ representation theory to derive provably rotation-invariant descriptors. While spherical harmonic coefficients transform equivariantly under rotations, the natural invariant constructions are typically limited to zeroth-order statistics which eliminate directional information and severely constrain embedding capacity. In this work, we introduce a principled third-order invariant construction by coupling higher-order $SO(3)$ irreducible representations via tensor products and projecting onto the trivial representation. This yields a spherical invariant bispectrum that preserves phase information while remaining strictly rotation-invariant. Leveraging this property, we embed watermarks into higher-order spherical harmonic coefficients and recover them from invariant bispectral scalars, enabling reliable extraction under arbitrary 3D rotations. We provide a theoretical proof of $SO(3)$ invariance for it and demonstrate experimentally its near-perfect robustness to continuous rotations while maintaining high visual fidelity.

10.
arXiv (math.PR) 2026-06-17

Full $\Gamma-$expansion for the level-two large deviation rate functionals of non-reversible one-dimensional diffusions with periodic boundary conditions

arXiv:2606.17859v1 Announce Type: new Abstract: Consider the diffusion process \begin{equation*} dX_{\epsilon}(t) = \mss b(X_{\epsilon}(t)) \, dt + \sqrt{2\, \epsilon\, \mss a(X_\epsilon(t))} \, dW_{t}, \end{equation*} on the one-dimensional torus $\bb T = [0,1)$. Here $\epsilon$ is the temperature, $W_{t}$ a Brownian motion on $\bb T$ and $\mss a$, $\mss b$ functions of class $C^{2}(\bb T)$ satisfying further conditions. Denote by $\mss P(\bb T)$ the set of probability measures on $\bb T$ equipped with the weak topology, and by $\ms I_{\epsilon}\colon \mss P(\bb T)\to [0,+\infty)$ the level two large deviation rate functional of the diffusion $X_{\epsilon}(\cdot)$. We derive a full $\Gamma-$expansion of $\ms I_{\epsilon}$, as $\epsilon \to 0$, expressing it as \begin{equation*} \ms I_{\epsilon} = \frac{1}{\epsilon} \;\ms J^{(-1)} \; +\; \ms J^{(0)} \;+\; \sum_{p=1}^{\widehat{\mf q}}\frac{1}{\theta^{(p)}_{\epsilon}}\;\ms J^{(p)}\,, \end{equation*} where $\ms J^{(-1)}$, $\ms J^{(0)}$, $\ms J^{(p)} \colon \mss P(\bb T)\to [0,+\infty]$ represent rate functionals, independent of $\epsilon$, and $\theta^{(p)}_{\epsilon}$ are the time-scales at which the Markov process $X_{\epsilon}(\cdot)$ exhibits a metastable behaviour.

11.
arXiv (quant-ph) 2026-06-15

Modeling light-matter coupled systems with neural quantum states

arXiv:2606.14352v1 Announce Type: cross Abstract: Recent advances in cold atom manipulation enable the study of many-body systems where short-range interactions between neighboring atoms coexist with long-range interactions mediated by photons. Such a combination of interactions makes a theoretical approach challenging beyond mean-field methods. In this work, we develop a neural quantum state based approach to study these systems numerically. We introduce a neural-network architecture capable of handling hybrid Hilbert spaces with large local bosonic dimensions in strongly interacting spin-photon systems. We benchmark this approach on a model of a two-dimensional lattice of Rydberg atoms coupled to a photon mode. The superradiant ground states found in the large spin-photon coupling regime allow us to demonstrate the efficiency of the method in the presence of high photon occupation. Furthermore, the ability to capture spin-spin and spin-photon correlations leads us to observe quantitative deviations in the ground state phase boundaries with respect to mean-field theory. The method extends to other systems with a similar hybrid Hilbert space structure, such as spin-phonon systems, and provides a scalable framework for investigating their ground state properties.

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

Bridging Functional Correctness and Runtime Efficiency Gaps in LLM-Based Code Translation

While large language models (LLMs) have greatly advanced the functional correctness of automated code translation systems, the runtime efficiency of translated programs has received comparatively little attention. With the waning of Moore's law, runtime efficiency has become increasingly important for program quality, alongside functional correctness. Our preliminary study reveals that LLM-translated programs often run slower than human-written ones, and this issue cannot be remedied through prompt engineering alone. Therefore, our work proposes SwiftTrans, a code translation framework comprising two key stages: (1) Multi-Perspective Exploration, where MpTranslator leverages parallel in-context learning (ICL) to generate diverse translation candidates; and (2) Difference-Aware Selection, where DiffSelector identifies the optimal candidate by explicitly comparing differences between translations. We further introduce Hierarchical Guidance for MpTranslator and Ordinal Guidance for DiffSelector, enabling LLMs to better adapt to these two core components. To support the evaluation of runtime efficiency in translated programs, we extend existing benchmarks, CodeNet and F2SBench, and introduce a new benchmark, SwiftBench. Experimental results across all three benchmarks show that SwiftTrans achieves consistent improvements in both correctness and runtime efficiency.

13.
arXiv (CS.AI) 2026-06-16

InstantForget: Update-Free Backdoor Unlearning with Inference-Time Feature Reset

Authors:

arXiv:2606.15730v1 Announce Type: cross Abstract: Backdoor unlearning aims to remove a malicious trigger behavior from a deployed model while preserving clean utility. We study the update-free inference-time setting, where model parameters remain frozen. First, we audit a common projection assumption under oracle paired clean and triggered features. Projection succeeds mainly on BadNets and leaves WaNet, Blended, and SIG at 0.683, 0.888, and 0.941 ASR on CIFAR-10 ResNet-18. This failure is not explained by spectral compactness, spatial locality, or subspace misalignment. It is predicted by a logit-triplet gap involving the target margin, target-logit drop, and non-target logit rise. We then introduce InstantForget, a clean-calibrated gated reset that flags anomalous features with a Mahalanobis score and moves only flagged features toward a neutral non-target representation. With one fixed operating point selected on held-out triggered validation, InstantForget reduces average ASR to 0.071 across four non-adaptive CIFAR-10 triggers without triggered samples or parameter updates at deployment. It also reaches 0.981 detection AUROC and transfers to six of eight tested backbones. Reported failures under WaNet, ModelNet10 point blend, two backbone geometries, and adaptive feature-compactness attacks define the method's scope.

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

VOID: Defeating Unauthorized Mimicry in Latent Diffusion Models

While Latent Diffusion Models (LDMs) have revolutionized visual synthesis, they are increasingly exploited for unauthorized mimicry of individuals. Existing defenses inject deceptive perturbations to steer the generated images toward irrelevant targets. However, this approach hinges on an ungrounded assumption: subtle perturbations can maintain their deceptive efficacy throughout an LDM's extensive generation process. In reality, the model's innate restoration mechanism will remove such perturbations and cause individual identities to re-emerge in the images generated. We propose VOID, a defense framework that overcomes this conundrum by manipulating an LDM's intrinsic stochasticity. VOID perturbs the diffusion pipeline in two novel ways: 1) amplifying the latent encoding errors to shatter an image's semantic structure, and 2) counteracting the target guidance signals to suppress the model's restoration capabilities. This results in a semantic corruption that thwarts any unauthorized mimicry. Notably, the security gain does not come at the price of visual utility, as VOID simultaneously manages to confine perturbations to human-imperceptible regions of protected images. Our comprehensive evaluation of 24 state-of-the-art defenses against 10 mimicry attacks on 5 datasets demonstrates VOID's unprecedented protection power: it increases the average Frechet Inception Distance (FID) from 113 to 365, a 223% improvement over the strongest defense to date.

15.
Nature (Science) 2026-06-08

Distributed control circuits across a brain-and-cord connectome

Just as genomes revolutionized molecular genetics, connectomes (maps of neurons and synapses) are transforming neuroscience. To date, the only organisms with complete connectomes are worms1–3, sea squirts4, and comb jellies5 (103–104 synapses). By contrast, the fruit fly is more complex (108 synaptic connections), with a brain that supports learning and spatial memory6,7 and an intricate ventral nerve cord analogous to the vertebrate spinal cord8–12. Here we report the first densely-reconstructed adult fly connectome that unites the brain and ventral nerve cord, and we leverage this resource to investigate principles of neural control. We show that effector neurons (motor neurons, endocrine cells, and efferent neurons targeting the viscera) are primarily influenced by sensory neurons in the same body part, forming local feedback loops. These local loops are linked by long-range circuits involving ascending and descending neurons organized into behavior-centric modules. Single ascending and descending neurons are often positioned to influence the voluntary movements of multiple body parts, together with the endocrine cells or visceral organs that support those movements. Brain regions involved in learning and navigation supervise these circuits. These results reveal an architecture that is distributed, parallelized, and embodied, reminiscent of distributed control architectures in engineered systems13,14.

16.
arXiv (CS.AI) 2026-06-17

Optimism Stabilizes Thompson Sampling for Adaptive Inference

arXiv:2602.06014v2 Announce Type: replace-cross Abstract: Thompson sampling (TS) is widely used for stochastic multi-armed bandits, yet its inferential properties under adaptive data collection are subtle. Classical asymptotic theory for sample means can fail because arm-specific sample sizes are random and coupled with the rewards through the action-selection rule. We study adaptive inference for Thompson sampling with Gaussian randomized indices in $K$-armed stochastic bandits with independent sub-Gaussian reward noises, and identify optimism as a key mechanism for restoring stability, meaning that each arm's pull count concentrates around a deterministic scale. This stability yields asymptotically valid Wald inference despite adaptive sampling. First, we prove that variance-inflated TS is stable for any $K \ge 2$, including the challenging regime where multiple arms are optimal, with asymptotically uniform allocation over optimal arms and sharp logarithmic pull-count asymptotics for suboptimal arms. This resolves the $K$-armed extension question raised by \citet{halder2025stable}, using new winner-map and Lyapunov-drift techniques to control allocation among multiple optimal arms. Second, we analyze an alternative optimistic modification that keeps the Gaussian index variance unchanged but adds an explicit mean bonus to the index center, and establish a similar stability conclusion. In summary, suitably implemented optimism stabilizes Thompson sampling and enables asymptotically valid Wald inference in multi-armed bandits, while incurring only a mild additional regret cost.

17.
Nature (Science) 2026-06-17

Molecular basis of polyadenylated RNA fate determination in the nucleus

Authors:

Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs1,2, which are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, including protein-coding RNPs, are exported to the cytoplasm, whereas transcripts within non-functional pA+ RNPs are degraded in the nucleus1–4. How cells distinguish these opposing fates remains unknown. The DExD-box ATPase UAP56 (also known as DDX39B) is a central component of functional pA+ RNPs, and promotes their docking to the nuclear pore complex-anchored TREX-25,6, which triggers transcript release from UAP56 to facilitate export7. Here we reveal that the poly(A) tail exosome targeting (PAXT) connection8 binds a TREX-2-like module, which releases pA+ RNAs from UAP56 for decay by the nuclear exosome. The core of this module consists of a LENG8–PCID2–SEM1 trimer, which we show is structurally and biochemically equivalent to the central GANP–PCID2–SEM1 trimer of TREX-2. Mutagenesis and transcriptomic data demonstrate that the nuclear fate of pA+ RNPs is governed by the contending actions of nucleoplasmic PAXT and nuclear pore complex-associated TREX-2, which interpret RNA-bound UAP56 as a signal for RNA decay or export, respectively. As RNA targets of PAXT are generally short and intron-poor, we propose an overall model for pA+ RNP fate determination whereby the distinct sub-nuclear localizations of PAXT and TREX-2 govern the degradation of short non-functional pA+ RNAs while allowing export of their longer and functional counterparts. Biochemical, structural and cell biological analyses reveal that UAP56 (DDX39B) assembles with a TREX-2–like module that redirects non-functional polyadenylated RNAs from export to degradation.

18.
arXiv (CS.CV) 2026-06-16

RaLMPH: Reliability-aware Learning for Multi-Pathologist Harmonization in Whole-Slide Image Classification

Multiple Instance Learning (MIL) is a standard paradigm for Whole-Slide Image (WSI) analysis and has achieved strong results in computational pathology. However, most MIL pipelines assume a single "gold" label per slide, which conflicts with clinical practice where substantial inter-pathologist variability is common. Existing multi-annotator learning and label-refinement methods typically estimate global annotator reliability or rely on single-instance assumptions, making them poorly suited to MIL and to localized diagnostic contexts where experts disagree. We propose RaLMPH (Reliability-aware Learning for Multi-Pathologist Harmonization), a MIL-based label reconciliation framework for WSIs annotated by multiple pathologists. RaLMPH introduces a reliability field that jointly models (i) local neighborhood structure in WSI feature space and (ii) expert uncertainty (entropy), enabling per-sample identification of trustworthy reference neighborhoods. Leveraging this field, RaLMPH performs sample-wise local annotator ranking to select reliable opinions per slide and applies an adaptive gating mechanism to fuse labels conditioned on local reliability. Experiments on a clinical WSI dataset with labels from six pathologists, as well as controlled simulated benchmarks, show that RaLMPH consistently outperforms existing approaches. Further analyses clarify how our reliability-aware mechanism improves label reconciliation and downstream MIL performance.

19.
medRxiv (Medicine) 2026-06-17

Real-World Effectiveness and Safety of Avacopan in ANCA-Associated Vasculitis: A Systematic Literature Review and Meta-analysis

Background: The efficacy and safety of avacopan in ANCA-associated vasculitis (AAV) has been established in randomized trials of of avacopan as a glucocorticoid (GC) sparing therapy. However, real world evidence (RWE) has an important role in confirming effectiveness and evaluating safety in more generalizable settings. This study aimed to synthesize RWE on the effectiveness and safety of avacopan in adults with AAV. Methods: A systematic literature review and meta analysis of non interventional real world studies was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Eligible studies included adults with AAV treated with avacopan in routine clinical practice. Pooled estimates of effectiveness and safety outcomes were calculated using random effects meta-analyses. Primary outcomes included remission at 6 and 12 months and sustained remission at 12 months. Secondary outcomes included relapse, GC use and dosing, hepatotoxicity, infections, and treatment discontinuation. Exploratory outcomes included changes in estimated glomerular filtration rate (eGFR) and dialysis related endpoints. Results: A total of 71 studies were included and contributed to quantitative analyses. Pooled remission for patients on avacopan was 87% (95% CI: 75%-94%) at 6 months and 93% (95% CI: 86%-97%) at 12 months, and sustained remission was 86% (95% CI: 74%-93%) at 12 months. Relapse at 12 months was low (7%; 95% CI: 4%-11%). GC use was 36% at both 6 and 12 months. Improvements in eGFR were observed at 6 months (18 mL/min/1.73 m2) and 12 months (18 mL/min/1.73 m2), and dialysis liberation was 66% in a limited subset. Among avacopan patients, 11% experienced any hepatotoxicity, including 7% with serious (defined as directly reported or requiring hospitalization) hepatotoxicity, while 7% experienced serious (defined as directly reported or requiring hospitalization) infection. Conclusions: In real world clinical practice, avacopan is associated with high remission rates, low relapse rates, and a consistent GC sparing effect, with effectiveness comparable to standard of care regimens. Findings support its clinical use with appropriate safety monitoring; however, the observed heterogeneity in hepatotoxicity and the limited comparative effectiveness evidence highlight areas requiring further investigation.

20.
arXiv (CS.CL) 2026-06-19

Beyond Uniform Forgetting: A Study of Sequential Direct Preference Optimization Across Preference Settings

Aligning language models with human preferences often requires optimising multiple behavioural objectives. A practical approach is to apply these objectives sequentially using preference optimisation methods such as Direct Preference Optimisation (DPO), but it remains unclear whether later training uniformly degrades preferences learned earlier or whether the effect depends on the relationship between objectives. We study sequential DPO across four preference settings covering distributional conflict, multi-attribute interaction, strong safety signal, and compatible response-quality objectives. Using Llama-3.1-8B-Instruct with LoRA adapters, we evaluate all objectives after every stage with a fixed base-model reference. We find that sequential DPO does not produce a single forgetting pattern; preference change ranges from partial degradation to stability, pair-level redistribution, or positive transfer depending on objective relationship, signal strength, and training order. Pair-level analysis using length-normalised policy margins shows that aggregate metrics can mask heterogeneous changes across preference pairs, whereas quartile decomposition reveals that high-confidence pairs can either degrade or improve depending on the setting. Mechanistic diagnostics show that Stage~2 gradients and adapter updates are near-orthogonal to the previous objective across all settings, providing little evidence that direct gradient opposition is the primary driver. These findings suggest that future sequential alignment pipelines should account for objective compatibility and signal strength, rather than assuming that later objectives affect earlier preferences uniformly.

21.
arXiv (quant-ph) 2026-06-16

Accelerating physics-informed neural networks for full waveform inversion using a hybrid quantum-classical finite-basis architecture

arXiv:2606.01110v2 Announce Type: replace-cross Abstract: Full waveform inversion (FWI) reconstructs heterogeneous material properties from receiver data but remains computationally demanding. Physics-informed neural networks (PINNs) and their domain-decomposed variants (FBPINNs) offer a mesh-free alternative but face convergence challenges when representing complex velocity fields. We present a hybrid quantum-classical FBPINN for acoustic FWI, bringing together quantum computing and classical machine learning, in which the decomposed wavefield network and the global velocity network are implemented as classical-to-quantum pipelines terminating in parameterized quantum circuits (PQCs). The PQCs are realized as differentiable JAX statevector simulators, enabling end-to-end automatic differentiation through the classical PINN, the quantum circuit, and the physics-informed loss. On a geophysical anomaly benchmark, the quantum hybrid reaches a lower L1 velocity error than the primary classical FBPINN baseline in approximately 8x fewer training iterations, despite using approximately 33% fewer trainable parameters, and it outperforms all 15 classical hyperparameter variants tested. A second benchmark (checkerboard) demonstrates the generality of the inversion pipeline, confirming that the quantum hybrid architecture can recover structured spatial variations beyond the localized anomaly benchmark. Our framework is broadly applicable to wave-based inverse problems beyond geophysics, including medical ultrasound tomography and non-destructive evaluation.

22.
arXiv (CS.LG) 2026-06-12

TEDD: Robust Detection of Unstable Temporal Features

arXiv:2606.12643v1 Announce Type: new Abstract: When working with real-world temporal data, it is common to encounter features whose distribution is changing over time. The naive employment of Machine Learning models on this unstable data might lead to rapidly degrading performance, especially if the new distribution is much different from what was previously seen during training. In order to cope with this problem, it is critical to automatically identify features that are changing over time. With these features detected, data scientists and other practitioners will be able to mitigate the issue (for instance, by applying data transformations), deploying more robust models that retain high performance for longer periods of time. In this paper, we describe which temporal changes a feature should not suffer from, and propose TEDD, a technique to a) identify when a dataset might lead to an unstable Machine Learning model and b) automatically detect which features cause such lack of robustness. In order to achieve it, we leverage a regression model to highlight which features contribute to a good prediction of an instance's timestamp. We compare our approach to other methods in real and synthetic data, testing their detection capability on all simple change patterns. We show that our method: detects all types of basic changes, both for numerical and categorical features; can detect multivariate drifts; returns a comparable value measuring the amount of change of each feature; requires no parameter tuning; and is scalable both on number of features and instances of the dataset.

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

Towards Engineering Scaling Laws with Pretraining Data Composition

arXiv:2606.19781v1 Announce Type: cross Abstract: Neural scaling laws describe how model performance improves as a power law in compute, model size, and dataset size. While well-established for large language models, these relationships are emerging for large models in particle physics. As with language, empirical studies show that the performance scales as a power law. However, unlike natural language or image domains, fundamental physics has high-fidelity simulators that produce synthetic data cheaply. This favors scaling regimes where additional data is cheaper than additional parameters, and allows the pretraining dataset itself to be engineered to influence the scaling. For the task of classifying hadronic jets produced in collisions of high-energy particle beams, we show that the scaling behavior can be engineered towards requiring more data rather than larger models by inclusion of pretraining data which is more diverse and better aligned with the downstream classification task.

24.
arXiv (CS.AI) 2026-06-18

scGTN: Deep Siamese Graph Transformer Network for Single-cell RNA Sequencing Clustering

arXiv:2606.18672v1 Announce Type: cross Abstract: Single-cell RNA sequencing (scRNA-seq) serves a pivotal role in characterizing gene expression at the cellular level, enabling the identification of cell types and advancing the understanding of cellular heterogeneity. Despite the significant progress in scRNA-seq data clustering, we argue that current methods always ignore the sparsity and noise, as well as the complex intercellular structural information inherent in scRNA-seq data. Toward this end, in this paper, we propose a novel single-cell RNA-seq clustering framework via deep Siamese Graph Transformer Network (termed scGTN), which explicitly integrates gene expression profile and intercellular structural dependencies for cell clustering. In particular, we formulate scRNA-seq data as a graph and construct two augmented graph views that serve as dual views to capture complementary intercellular information. Then, a Siamese graph transformer network is employed to explicitly incorporate shortest-path information and node-wise distances for capturing richer structural relationships between cells. Finally, we employ an optimal transport strategy to guide the cell clustering in a self-supervised manner. Extensive experiments on multiple benchmark scRNA-seq datasets demonstrate that our scGTN consistently outperforms existing methods. Our code is available at https://github.com/W-RMSL/scGTN.

25.
arXiv (CS.CL) 2026-06-17

Dissociating Decodability and Causal Use in Bracket-Sequence Transformers

When trained on tasks requiring an understanding of hierarchical structure, transformers have been found to represent this hierarchy in distinct ways: in the geometry of the residual stream, and in stack-like attention patterns maintaining a last-in, first-out ordering. However, it remains unclear whether these representations are causally used or merely decodable. We examine this gap in transformers trained on the Dyck language (a formal language of balanced bracket sequences), where the hierarchical ground truth is explicit. By probing and intervening on the residual stream and attention patterns, we find that depth, distance, and top-of-stack signals are all decodable, yet their causal roles diverge. Specifically, masking attention to the true top-of-stack position causes a sharp drop in long-distance accuracy, while ablating low-dimensional residual stream subspaces has comparatively little effect. These results, which extend to a templated natural language setting, suggest that even in a controlled setting where the relevant hierarchical variables are known, decodability alone does not imply causal use.