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01.
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.

02.
arXiv (CS.LG) 2026-06-12

PhysMetrics.Weather: An Evaluation Framework for Physical Consistency in ML Weather Models

arXiv:2606.10642v2 Announce Type: replace Abstract: Machine learning weather prediction (MLWP) models have achieved impressive forecasting performance at a small fraction of the computational costs required for traditional physics-based methods. However, they are primarily (1) data-driven and (2) evaluated using pixel-wide error metrics (e.g., RMSE), so there are no guarantees that their forecasts are consistent with known physical laws. We introduce PhysMetrics$.$Weather, an evaluation framework that assesses the physical realism of MLWP models across three types of metrics: conservation, spectral, and dynamical. By quantifying physical realism, this tool guides the development of physics-informed architectures and helps evaluate whether MLWP models are reliable for operational use. Our framework is available on Github at https://github.com/Emmakast/PhysMetrics.Weather.

03.
arXiv (CS.CL) 2026-06-24

Does My Embedding Reflect That $A = B$? Evaluating Mathematical Equivalence in Embedding Models

Because mathematics is highly abstract, a single statement can take very different forms depending on what subfield it is framed in. There are many examples where breakthroughs occurred after researchers discovered that a question had already been answered in a different field. At the same time, the growth of new resources related to formalization has increased the need for tools that enable efficient and reliable navigation between mathematical 'languages' (e.g., from Lean to natural language). In this paper, we investigate whether current embedding models capture mathematical equivalence. To do this, we introduce the Mathematically Equivalent but Lexically Different Pairs (MELD) Dataset, a collection of mathematically equivalent statements that are expressed in very different language. We show that current state-of-the-art embedding models tend to group statements by the terminology used to make them instead of the underlying math. Motivated by this, we propose a contrastive approach to learning embeddings of mathematical text that focuses on aligning informal statements with different formalizations. Our experiments demonstrate that this leads to improvements not only on informal-formal retrieval tasks but also on MELD, which only contains natural language statements.

04.
bioRxiv (Bioinfo) 2026-06-11

GeroEngine: Generative single-cell aging trajectories reveal a bidirectionally traversable identity core and direction-specific inflammatory remodeling

Authors:

Single-cell RNA sequencing (scRNA-seq) maps aging tissues at high resolution but is destructive, preventing longitudinal tracking; dropout and zero-inflation artifacts, amplified by shift-invariant linear simulations, confound age-associated variability. We developed GeroEngine, a technical-artifact-aware framework combining VAE-based trajectory simulation, LOPO cross-validation, linear baselines, reverse traversal, and reverse-directed network inference. In microglia and HSCs, the VAE reduced technical-artifact carryover while preserving trajectory heterogeneity and improving alignment to artifact-reduced reference manifolds. Consensus GeroTargets and GeroRegulators defined tissue-specific GeroNetworks organized into three pillars: lineage/replication identity collapse, a sex-dimorphic endocrine/stress core, and inflammatory remodeling. Forward and reverse simulations aligned to the common young[->]old aging axis revealed a sign-coherent, direction-specific program: identity/replication targets were bidirectionally recovered, whereas MHC/NF-{kappa}B inflammatory programs were preferentially forward-recovered. These results support identity collapse as a deep traversable core of aging and nominate upstream homeostatic restoration over downstream inflammatory suppression.

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

IGLU: The Integrated Gaussian Linear Unit Activation Function

Activation functions are fundamental to deep neural networks, governing gradient flow, optimization stability, and representational capacity. Within historic deep architectures, while ReLU has been the dominant choice for the activation function, modern transformer-based models increasingly are adopting smoother alternatives such as GELU and other self-gated alternatives. Despite their empirical success, the mathematical relationships among these functions and the principles underlying their effectiveness remains only partially understood. We introduce IGLU, a parametric activation function derived as a scale mixture of GELU gates under a half-normal mixing distribution. This derivation yields a closed-form expression whose gating component is exactly the Cauchy CDF, providing a principled one-parameter family that continuously interpolates between identity-like and ReLU-like behavior via a single sharpness parameter $\sigma$. Unlike GELU's Gaussian gate, IGLU's heavy-tailed Cauchy gate decays polynomially in the negative tail, guaranteeing non-zero gradients for all finite inputs and offering greater robustness to vanishing gradients. We further introduce IGLU-Approx, a computationally efficient rational approximation of IGLU expressed entirely in terms of ReLU operations that eliminates transcendental function evaluation. Through evaluations on CIFAR-10, CIFAR-100, and WikiText-103 across ResNet-20, ViT-Tiny, and GPT-2 Small, IGLU achieves competitive or superior performance on both vision and language datasets against ReLU and GELU baselines, with IGLU-Approx recovering this performance at substantially reduced computational cost. In particular, we show that employing a heavy-tailed gate leads to considerable performance gains in heavily imbalanced classification datasets.

06.
arXiv (CS.CL) 2026-06-15

SuperThoughts: Reasoning Tokens in Superposition

Long Chain-of-Thought (CoT) reasoning improves LLM problem-solving but is computationally expensive due to sequential token generation. While recent works explore reasoning in continuous latent spaces to bypass discrete token generation, they often struggle with training stability and fail to scale to complex, long-horizon tasks due to lack of supervision signal. We propose SuperThoughts, which compresses pairs of consecutive CoT tokens into single latent representations and decodes two tokens per step via a lightweight Multi-Token Prediction (MTP) module. This preserves discrete token supervision at training time while doubling throughput at inference time. We finetune Qwen2.5-Math-1.5B-Instruct, Qwen2.5-Math-7B-Instruct, Qwen2.5-Math-14B-Instruct, and evaluate on MATH500, AMC, OlympiadBench, and GPQA-Diamond. With a confidence-based adaptive mechanism that falls back to standard decoding when uncertain, SuperThoughts achieves $\sim$20–30\% CoT length reduction while maintaining accuracy with minimal degradation (1-2 points accuracy drop on most tasks).

07.
arXiv (CS.CL) 2026-06-16

The Art of Mixology: Mixup-based Obfuscation for Privacy-Preserving Split Learning in Large Language Models

Split learning provides a practical paradigm for resource-constrained users to train Large Language Models (LLMs) by offloading computation-intensive layers to a server while keeping raw data local. However, existing privacy-preserving split learning methods still face a difficult trade-off among utility, privacy, efficiency, and stability. Specifically, these methods often suffer from substantial utility degradation, remain vulnerable to advanced data reconstruction attacks, incur prohibitive computational and communication overhead, or exhibit unstable performance across different tasks. In this paper, we propose MIXGUARD, a novel mixup-based privacy-preserving split learning framework for LLMs. MIXGUARD introduces token-level obfuscation, representation-level obfuscation, and adaptive gradient perturbation mechanisms, which operate jointly to preserve useful learning signals while preventing privacy leakage to the server. Technically, MIXGUARD first constructs a lightweight calibration model on a public dataset to refine the approximated target representation, and then applies this model during privacy-preserving fine-tuning on private data. We conduct extensive experiments on four classification tasks and four text generation tasks across multiple LLM families, model sizes, architectures, and fine-tuning strategies. The results show that MIXGUARD preserves model utility comparable to non-split training baselines, consistently achieves stronger privacy protection than existing split learning defense methods against state-of-the-art data reconstruction attacks, and remains robust under adaptive attack settings.

08.
PLOS Medicine 2026-06-23

Multi-omics biomarkers of endothelial dysregulation preceding chronic lung allograft dysfunction: A prospective cohort study

Authors:

by Giulia Iacono, Christina Begka, Bailey Cardwell, Carmel Daunt, Roxanne Chatzis, Celine Pattaroni, Alana Butler, Matthew Macowan, Bronwyn Levvey, Gregory I. Snell, Glen P. Westall, Benjamin J. Marsland Background Long-term survival of lung transplant recipients remains limited by chronic lung allograft dysfunction (CLAD). CLAD is only diagnosed following a persistent and substantial decline in lung function, after which irreversible damage to the lungs has occurred, limiting opportunities to effectively intervene at an early stage. There is a critical need for earlier detection prior to its clinical manifestation. The immunological drivers of CLAD remain unclear, limiting the development of predictive biomarkers and new therapies. Methods and findings In this hypothesis-generating, prospective cohort study, we profiled the microbial, metabolic, lipidomic, and gene expression dynamics of longitudinally collected broncho-alveolar lavages (BALs) from 56 CLAD-free lung transplant recipients up to 30 months post-transplant, and compared BALs from 13 CLAD-free patients to BALs from 13 patients who developed CLAD. In CLAD-free patients, the first 6 months post-transplant were hallmarked by diminished microbial diversity and increased abundance of Staphylococcus and Candida, coupled with upregulated innate and adaptive immune responses, and elevated nitric oxide metabolism (FDR 

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

Identifiable Markov Switching Models with Instantaneous Effects and Exponential Families

arXiv:2606.02231v2 Announce Type: replace-cross Abstract: Temporal systems often exhibit non-stationary behaviour, such as seasonal climate variation or glucose fluctuations in patients with type-1 diabetes. One way to model non-stationarity is through discrete latent regimes, i.e., stationary segments of time. Such systems induce a Markov Switching Model (MSM), a class of Hidden Markov Models with autoregressive dependencies among latent regimes and observed variables. Identifying latent regimes is challenging in the presence of frequent regime switches and nonlinear and non-Gaussian dynamics, particularly when there are instantaneous effects between the variables, e.g., due to slow rates of measurements. In this work, we establish the identifiability of both latent regimes and regime-dependent causal structures under temporal regime dependencies, nonlinear lagged and instantaneous effects, and independent noise from the exponential family. Our identifiability theory subsumes non-temporal mixtures of causal models. Furthermore, we introduce FlowMSM, a regime detection framework that can be paired with any stationary causal discovery method to recover regime-dependent causal structures. Experiments on synthetic benchmarks and a financial economics dataset demonstrate the effectiveness of our approach to detect latent regimes and discover causal structures from non-stationary time series.

10.
arXiv (CS.CV) 2026-06-24

HANCLIP: A Family of Hyperbolic Angular Negation Vision Language Models

Vision-Language Models (VLMs) are typically pre-trained on large-scale image-text datasets to capture semantic correspondences between visual content and natural language. However, they remain surprisingly brittle to negation: models often rely on shallow word co-occurrence and are easily distracted by misleading or irrelevant textual cues, even when their overall retrieval or classification performance is strong. Moreover, directly finetuning on negation data can interfere with previously acquired knowledge, causing noticeable degradation on standard vision-language benchmarks. To tackle these issues, this work introduces HANCLIP (Hyperbolic + Angular + Negation), a family of VLMs that explicitly restructures the embedding space to encode "what an image is not" alongside "what it is." HANCLIP is trained on a compact set of 20,000 image-text quadruplets and combines a hyperbolic formulation, which models hierarchical semantic relations and asymmetries, with an angular triplet objective that drives systematic separation between negated descriptions and their corresponding positives. This geometry-aware design strengthens negation sensitivity while preserving the global structure of pretrained representations, rather than overwriting them. Extensive experiments across multiple vision-language tasks show that HANCLIP delivers consistent gains on the negation-focused NegBench benchmark, while maintaining competitive or improved performance on standard classification and image-text retrieval benchmarks. The framework is model-agnostic and can be plugged into CLIP, LongCLIP, SmartCLIP, and HiMo-CLIP without large-scale retraining, demonstrating that a carefully designed geometric objective can substantially extend the reasoning capabilities of existing VLMs using only modest additional data.

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

MoonSplat: Monocular Online Gaussian Splatting with Sim(3) Global Optimization

Online 3D reconstruction from monocular image sequences is a challenging and ongoing research topic. 3D Gaussian Splatting (3DGS), leveraging its high-quality real-time rendering capability, empowers online 3D reconstruction to represent dense scenes with enhanced expressiveness, and thus holds great promise for a wide range of applications such as robotics and AR/VR. However, existing online 3DGS methods still suffer from some key challenges: fragile camera pose estimation due to the lack of global optimization, and low optimization efficiency in large-scale or long-sequence scenarios. To address these issues, we propose a robust and efficient online voxelized 3DGS reconstruction framework integrated with global $Sim(3)$ optimization, which enables reliable camera tracking and efficient global loop closure for both camera poses and voxelized 3DGS. To accelerate the convergence of the voxelized 3DGS, we further introduce a color residual learning strategy, which not only boosts optimization speed but also enhances rendering quality. Extensive experiments on diverse indoor and outdoor datasets demonstrate that our method achieves state-of-the-art performance in both camera pose estimation accuracy and rendering quality, while retaining real-time efficiency. Additionally, we develop and deploy a real-world UAV-based active reconstruction system grounded on our proposed method, validating its robustness and generalizability for practical online 3D reconstruction tasks. Our code and data are available at https://github.com/TrickyGo/MoonSplat.

12.
arXiv (CS.AI) 2026-06-12

Fin-RATE: A Real-world Financial Analytics and Tracking Evaluation Benchmark for LLMs on SEC Filings

arXiv:2602.07294v4 Announce Type: replace-cross Abstract: With the increasing deployment of Large Language Models (LLMs) in the finance domain, LLMs are increasingly expected to parse complex regulatory disclosures. However, existing benchmarks often focus on isolated details, failing to reflect the complexity of professional analysis that requires synthesizing information across multiple documents, reporting periods, and corporate entities. Furthermore, these benchmarks do not disentangle whether errors arise from retrieval failures, generation inaccuracies, domain-specific reasoning mistakes, or misinterpretation of the query or context, making it difficult to precisely diagnose performance bottlenecks. To bridge these gaps, we introduce Fin-RATE, a benchmark built on U.S. Securities and Exchange Commission (SEC) filings and mirroring financial analyst workflows through three pathways: detail-oriented reasoning within individual disclosures, cross-entity comparison under shared topics, and longitudinal tracking of the same firm across reporting periods. We benchmark 17 leading LLMs, spanning open-source, closed-source, and finance-specialized models, under both ground-truth context and retrieval-augmented settings. Results show substantial performance degradation, with accuracy dropping by 18.60% and 14.35% as tasks shift from single-document reasoning to longitudinal and cross-entity analysis. This degradation is associated with increased comparison hallucinations, temporal and entity mismatches, and is further reflected in declines in reasoning quality and factual consistency–limitations that existing benchmarks have yet to formally categorize or quantify.

13.
arXiv (CS.CL) 2026-06-17

SuCo: Sufficiency-guided Continuous Adaptive Reasoning

Despite remarkable performance on complex tasks, Large Reasoning Models (LRMs) often generate excessively long Chain-of-Thoughts (CoT), inflating computational costs even for simple queries. Existing efforts to mitigate this inefficiency typically rely on discrete reasoning modes or fixed budget tiers, lacking a principled criterion of when reasoning is sufficient. In this work, we introduce Minimal Sufficient CoT (MSC), defined as the shortest prefix of a CoT trajectory which is adequate for producing the correct answer. We empirically show that MSC not only reduces reasoning tokens, but also improves accuracy across difficulty levels. Building on MSC, we propose Sufficiency-guided Continuous Adaptive Reasoning (SuCo), a two-stage training framework for autonomous reasoning control along a continuous spectrum. In stage 1, MSC-Aligned Fine-Tuning (MFT) constructs MSC data using problem-adaptive sufficiency thresholds that naturally scale with question difficulty, then fine-tunes the model to internalize concise yet sufficient reasoning patterns. In stage 2, Sufficiency-Aware Policy Optimization (SAPO) further optimizes the model through reinforcement learning with dynamic complexity tracking and sufficiency-aware rewards that penalize both over- and under-thinking. Extensive experiments across mathematics, code, and science benchmarks show that SuCo consistently achieves improvements in both accuracy and reasoning efficiency.

14.
arXiv (CS.LG) 2026-06-17

When Dynamics Models Read the Wrong Time Steps: Label-Free Event Credit Re-Anchoring for Robust Global Readouts

Authors:

arXiv:2606.17572v1 Announce Type: new Abstract: Learned dynamics models often answer global physical questions, such as fault severity or impact stiffness, by pooling a per-step feature sequence into one readout vector. This sequence-to-global interface creates an under-studied temporal credit problem: with only trajectory-level supervision, a model can predict accurately in training conditions while reading from abundant smooth correlates rather than the brief physical events that determine the target. We call this failure temporal credit dilution. It is not exposed by the training loss and is not removed by standard physics-informed residuals, because the error lies in where the global readout assigns functional credit. We introduce Credit-in-Event, an interface-level probe for measuring how much pooled credit lands on event steps, and prove in closed form that a pooled linear reader routes credit to a spurious background channel as the event fraction shrinks. We then propose CREST, a training-free and label-free readout that estimates a transient event core from learned features and re-anchors the pooled representation through event-versus-rest contrast. Across simulated gear and impact systems, recurrent and attention encoders, and public bearing vibration data, CREST reduces out-of-distribution error while restoring event credit. Ablations show that stable-step selection and receptive-field shrinking fail, confirming that the gain comes from event-core credit re-anchoring rather than a generic locality or stability prior.

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

Feature Attribution in Directed Acyclic Graphs Using Edge Intervention

arXiv:2606.15273v1 Announce Type: new Abstract: Shapley value-based feature attribution methods face challenges in scenarios involving complex feature interactions and causal relationships, even when a causal structure is provided. Existing methods typically adopt a node-centric view, attributing importance solely to individual features. Consequently, they often fail to simultaneously capture the externality and exogenous influence of features, leading to unreasonable interpretations. To overcome these limitations, we propose a novel feature attribution method called DAG-SHAP, which is based on edge intervention. DAG-SHAP treats each feature edge as an individual attribution object, ensuring that both externality and exogenous contributions of features are appropriately captured. Additionally, we introduce an approximation method for efficiently computing DAG-SHAP. Extensive experiments on both real and synthetic datasets validate the effectiveness of DAG-SHAP. Our code is available at https://github.com/ZJU-DIVER/DAG-SHAP.

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

QC-GAN: A Parameter-Efficient Quaternion Conformer GAN for High-Fidelity Speech Enhancement

arXiv:2606.18611v1 Announce Type: cross Abstract: We propose a parameter-efficient speech enhancement framework, Quaternion Conformer GAN (QC-GAN), which combines a Quaternion Conformer generator with MetricGAN-based training. The Hamilton product encodes the magnitude and phase via structured weight sharing, reducing the number of layer parameters while preserving their interdependencies. A metric-learning discriminator was employed to maximize perceptual quality by optimizing the approximate perceptual evaluation scores. On the VoiceBank+DEMAND dataset, QC-GAN achieved a Perceptual Evaluation of Speech Quality (PESQ) score of 3.48 with only 0.89M parameters, delivering a performance comparable to state-of-the-art models at less than half their size. A 35K-parameter variant achieved a PESQ score of 3.23, surpassing conventional methods with significantly fewer parameters. Evaluation on the DNS-Challenge 3 dataset further confirmed generalization to real-world conditions.

17.
arXiv (CS.CL) 2026-06-18

RCEM: Robust Conversational Search EMbedder in Distributional Shift

We propose RCEM, a Robust Conversational search EMbedder that is additionally equipped with LLM's query reformulation capability without losing base model's generalization. Unlike prior conversational dense retrieval approaches that learn direct conversation-to-passage matching, RCEM aligns conversations, prepended by special token, to LLM-rewritten queries, while preserving the original embedding space. The unchanged embedding space automatically maps the rewritten-query to the relevant passages. As a result, RCEM (1) reduces overfitting by simplifying the alignment task from long passages to shorter rewritten queries, (2) eliminates the need for conversation-to-passage relevance labels for training, and (3) maintains its original embedding space that allows conversational queries against indexes built by original embedder without rebuilding them. Extensive experiments show that RCEM consistently outperforms prior approaches, achieving up to 30% improvement under distributional shift.

18.
arXiv (CS.CV) 2026-06-15

MMRINet: Efficient Mamba-Based Segmentation with Dual-Path Refinement for Low-Resource MRI Analysis

Automated brain tumor segmentation in multi-parametric MRI remains a critical yet underserved challenge in resource-constrained clinical settings, where deep 3D networks requiring high-end GPUs are not viable. This is particularly acute across sub-Saharan Africa (SSA), where low-field scanners, heterogeneous patient demographics, and severe data scarcity compound the difficulty of applying standard deep learning pipelines. We present MMRINet, a lightweight segmentation architecture purpose-built for these constraints. At its core, MMRINet replaces quadratic-complexity self-attention with linear-complexity Mamba state-space models, enabling efficient long-range volumetric context modeling without the computational overhead of Transformer-based approaches. We combine two lightweight refinement components:Dual-Path Feature Refinement (DPFR), which extracts complementary detail and contextual representations to improve feature diversity under limited data, and Progressive Feature Aggregation (PFA), which hierarchically fuses multi-scale decoder outputs for sharper segmentation boundaries. Evaluated on the BraTS-Lighthouse SSA 2025 challenge dataset, comprising 3D MRI scans from Nigerian clinical sites, MMRINet achieves an average Dice score of 0.752 and an average HD95 of 12.23 mm with only ~2.5M parameters, outperforming all evaluated baselines, including UNETR, Swin-UNETR, SegMamba, and SegResNet3D. These results indicate that strong validation-set segmentation performance can be achieved with substantially reduced computation, offering a practical step toward AI-assisted neuro-oncology in low-resource clinical environments. Our GitHub repository can be accessed here: BioMedIA-MBZUAI/MMRINet.

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

Self-Generated Error Training for Token Editing in Diffusion Language Models

Authors:

Token-to-token (T2T) editing lets LLaDA2.1 revise committed tokens during block-diffusion decoding. The released recipe trains this editor on random vocabulary corruptions, but at inference the editor sees the model's own fluent, high-confidence draft errors instead. We study this training-inference mismatch and propose self-generated T2T, which performs a no-gradient draft pass, fills masked positions with predicted tokens, and supervises recovery in a second pass under these self-generated corruptions. We implement the update as a short LoRA continued-pretraining pass on LLaDA2.1-mini and evaluate on several benchmarks under the official Q-Mode T2T procedure with unchanged inference parameters. The method generally improves accuracy while reducing T2T edit intensity, mitigating failure modes such as final-digit transcription errors after otherwise correct reasoning and excessive self-correction before short factual answers.

20.
arXiv (CS.CL) 2026-06-11

Teaching Diffusion to Speculate Left-to-Right

Large language models (LLMs) achieve remarkable performance across a wide range of tasks, but their autoregressive decoding process incurs substantial inference costs due to inherently sequential token generation. Speculative decoding addresses this bottleneck by employing a lightweight draft model to propose multiple future tokens that are subsequently verified in parallel by a larger target model. Recent work has demonstrated that diffusion language models are well suited for this setting, as they can generate entire blocks of draft tokens in parallel and thereby alleviate the sequential constraints of autoregressive drafting. A subtlety of this regime is that block-diffusion drafters generate tokens bidirectionally within a block, whereas verification is performed by an autoregressive target model that evaluates tokens in a strictly left-to-right manner, leaving a gap between the symmetric training-time objective and the asymmetric verification-time reward. In this work, we offer an empirical analysis of three training-time interventions that narrow this gap: token positional weighting, a first-error focal loss that targets the position that breaks the accepted prefix within each block, and a chain loss term that substitutes a differentiable surrogate for the expected accepted length. The three interventions act along orthogonal axes (position, block-conditional first error, joint prefix) and compose additively; they are likewise orthogonal to test-time alignment mechanisms such as multi-draft self-selection, with which they can in principle be combined. Across four target models and six reasoning, code, and dialogue benchmarks, the three interventions raise accepted draft length by 21-76% per benchmark over a position-uniform baseline, without adding additional forward passes and without changing the inference pipeline or the rejection-sampling exactness contract.

21.
arXiv (quant-ph) 2026-06-11

Compressed minimum-purity time evolution for late-time quantum dynamics

arXiv:2606.11392v1 Announce Type: cross Abstract: Unitary time evolution of initially simple quantum many-body states rapidly generates entanglement and complex correlations, which limits direct numerical simulations. The late-time dynamics of physical observables, however, typically exhibits an effective simplicity in the form of hydrodynamics or kinetic theory. This leads to the question whether microscopic equations of motion can remain accurate and tractable up to long time scales by discarding irrelevant information in a controlled manner. Here, we introduce compressed minimum-purity time evolution (CoMPuTE) as an approach to keep track of a consistent set of reduced local density matrices, closing the hierarchical equations of motion using a minimum-purity principle. In benchmark applications we demonstrate (i) accurate description of energy diffusion in the one-dimensional mixed-field Ising model, (ii) the applicability to genuinely out-of-equilibrium Floquet dynamics starting from a pure state, and (iii) the limitations of the local reduced density matrix approximation when describing transport in the XXZ chain at $\Delta=1$ that is governed by increasingly non-local integrals of motion. The CoMPuTE method enhances computational efficiency in comparison to the closely related local-information time evolution algorithm, opening a possible route towards an extension to systems in higher spatial dimensions.

22.
PLOS Computational Biology 2026-06-10

Interpreting higher-order dependence in multimorbidity using cohort data: A partial information decomposition approach

by Cillian Hourican, Geeske Peeters, René J. F. Melis, Almar Kok, Natasja M. van Schoor, Sandra Wezeman, Mike Lees, Marcel G. M. Olde Rikkert, Rick Quax In the context of multimorbidity, clinical features seldom act in isolation: symptoms, signs and behaviours form interdependent systems in which joint effects on function can be demonstrated only when features are considered together. We introduce an open, reusable workflow that detects and interprets these “together-only” interactions using bivariate Partial Information Decomposition (PID; two sources to one target), linking synergy-based dependence to the broader network of clinical variables rather than to a single target. The workflow estimates synergy with small-sample bias correction and summarises each pair in a Breadth–Uniformity–Synergy–Total (BUST) map: breadth of synergy across target variables (broad “generalist” vs narrow “specialist” patterns), cross-stratum uniformity across age, sex and multimorbidity (uniform vs subgroup-specific), synergy strength, and total shared information. Simple diagnostics contrast observed targets with additive expectations, revealing the specific joint configurations through which non-additive effects arise. Applied to data from the Longitudinal Ageing Study Amsterdam, we treated all health-related variables—covering symptoms, clinical signs, behaviours, lifestyle factors, and self-rated health indicators—as both sources and targets in the PID framework. This symmetric design permits synergy to be quantified for every pair of variables with respect to every other variable. The workflow identifies synergistic constellations that additive models miss. Multidomain cliques involving subjective health, pain, cognition and grip strength showed multiple non-additive configurations, whereas pairs such as alcohol use with grip strength exhibited focused, narrow but uniform synergy. Notably, the pairs with the strongest synergistic contributions were largely distinct from those with the highest total mutual information, indicating that synergy captures dependency structure overlooked by conventional association measures. Rather than a new measure, this work provides a bias-aware workflow that makes higher-order dependence visible and transferable. Our results support synergy-aware mapping as a practical complement to conventional multimorbidity analyses: it highlights specific combinations of routinely assessed features whose joint states may be especially informative across multiple health targets and therefore candidates for prioritised joint assessment and future multi-domain intervention studies.

23.
medRxiv (Medicine) 2026-06-22

Impact of Antidiabetic Medications on IgG and Plasma Protein N-Glycosylation in Type 2 Diabetes Patients

Introduction. Diabetes is a growing global health challenge, necessitating effective management strategies. Glycosylation, a highly regulated post-translational protein modification, has emerged as a pivotal factor in diabetes pathophysiology. However, the modulation of protein glycosylation by antidiabetic treatment is still largely unknown. This study explored the longitudinal effects of four distinct antidiabetic therapies - metformin, insulin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1RA) - on plasma protein and immunoglobulin G (IgG) glycosylation in patients with type 2 diabetes (T2D). Research Design and Methods. Plasma protein and IgG N-glycans were enzymatically released, purified and chromatographically profiled in a cohort of 124 patients, examined at four time points, to assess therapy-induced glycan alterations. Linear mixed models adjusting for covariates and multiple testing (FDR

24.
Nature Medicine 2026-06-08

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

Authors:

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

25.
medRxiv (Medicine) 2026-06-19

Fine-Tuning SAM2 for Coronary Artery Segmentation in X-Ray Fluoroscopy

Authors:

SAM2 (Meta, 2024) provides a strong starting point for segmentation, but given the unique challenges in medical imaging (noise from patient movement, the projection-based nature of X-ray fluoroscopy, and low contrast between vessels and background), direct application is difficult. We fine-tune MedSAM2 on annotated coronary angiograms and apply it to video data for point-of-care use. On the ARCADE validation set (200 images), the fine-tuned model achieves Dice 0.767 compared to 0.033 zero-shot. On 10 fluoroscopic video studies from CoronaryDominance, it tracks vessels coherently and avoids falsely segmenting ribs, stents, and bypass grafts in 9 of 10 studies. Code is available at https://github.com/elakiyasivakumar/SAM2-Coronary-Angiography-VA and the fine-tuned checkpoint at https://huggingface.co/Elakiya17/CA-SAM2.