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

LoSoNA: A Benchmark for Local Social Norm Adaptation in Group Conversations

Online group chats are social spaces with local conversational norms that are rarely stated explicitly. The ability and willingness of LLM-based agents to recognize and adapt to these norms remains mostly unexplored. We introduce LoSoNA, a benchmark for local social norm adaptation in multi-party chat. Each scenario gives a subject model a curated group-chat transcript in which non-subject participants demonstrate a hidden local norm, followed by a final elicitor turn that forces a response revealing whether the subject has inferred that norm. We evaluate eight frontier and open-weight models under four prompting conditions that vary how explicitly the model is told to treat the prior conversation as evidence for how it should answer. Naive prompting remains limited for most models; explicit norm-aware prompting helps unevenly, with Gemini 3.1 Pro reaching $84.2\%$ and Claude Fable 5 reaching $81.6\%$, while several other models show small gains or regressions. LoSoNA contributes to recent calls for evaluating LLM social capabilities by testing whether models can infer local conversational norms from precedent and use them in a one-turn group-chat response.

02.
arXiv (CS.AI) 2026-06-16

From Overload to Convergence: Supporting Multi-Issue Human-AI Negotiation with Bayesian Visualization

arXiv:2603.22766v2 Announce Type: replace-cross Abstract: As AI systems increasingly mediate negotiations, understanding how the number of negotiated issues impacts human performance is crucial for maintaining human agency. We designed a human-AI negotiation case study in a realistic property rental scenario, varying the number of negotiated issues; empirical findings show that without support, performance stays stable up to three issues but declines as additional issues increase cognitive load. To address this, we introduce a novel uncertainty-based visualization driven by Bayesian estimation of agreement probability. It shows how the space of mutually acceptable agreements narrows as negotiation progresses, helping users identify promising options. In a within-subjects experiment (N=32), it improved human outcomes and efficiency, preserved human control, and avoided redistributing value. Our findings surface practical limits on the complexity people can manage in human-AI negotiation, advance theory on human performance in complex negotiations, and offer validated design guidance for interactive systems.

03.
arXiv (CS.LG) 2026-06-11

Higher-Order Token Interactions via Quantum Attention

arXiv:2606.11673v1 Announce Type: cross Abstract: Standard dot-product self-attention computes, in a single layer, only pairwise (order-2) interactions between tokens; representing a generic order-$k$ interaction is known to require either super-quadratic resources in one layer or composition across depth. We introduce Quantum Higher-Order Attention (QHA), a shallow, hardware-realizable quantum attention head that, via data re-uploading and an all-to-all non-Clifford entangler, synthesizes order-$k$ token interactions inside the circuit and exposes them through a local single-qubit read-out. We prove (i) an expressivity separation: any single standard self-attention layer with embedding dimension $m$, $H$ heads and $p$-bit precision satisfying $mHp=o(N/\log\log N)$ cannot represent the order-$k$ correlation family that one QHA head represents with circuit depth $O(\log k)$ ($O(k)$ two-qubit gates); and (ii) a trainability guarantee for its local-design instantiation: with a local read-out and $O(\log n)$ depth the gradient variance is $\Omega(1/\mathrm{poly}(n))$ (no barren plateau), which we confirm empirically – while being explicit that the more expressive all-to-all instantiation we benchmark is trained empirically and shows exponentially decaying gradients. Empirically, at a $6.5\times$ smaller parameter budget, QHA generalizes hidden-subset parity of every order $k\le6$ from disjoint inputs, whereas the larger classical attention head collapses past order~2; consistent with theory, the size of the advantage tracks the target's Fourier degree - largest for parity and shrinking when low-order structure is present. As an application, QHA serves as a compact high-order interaction detector across three domains - genetic epistasis, learning-parity-with-noise, and graph triangle detection - reaching the noise ceiling at the smallest parameter budget where field-standard linear methods fail.

04.
arXiv (CS.CV) 2026-06-17

RT-Counter: Real-Time Text-Guided Open-Vocabulary Object Counting

Text-guided open-vocabulary object counting (TOOC) aims to count objects belonging to the categories specified by natural language descriptions. Although vision-language pre-trained models have been successful applied to TOOC tasks, they still struggle with fine-grained spatial understanding and real-time inference requirements in counting scenarios. To address these limitations, this paper proposes a real-time TOOC framework, called the Real-Time Counter (RT-Counter), that achieves not only good counting accuracy but also high computational efficiency. RT-Counter designs a novel Visual Prototype Textualization (VPT) module that can project learned visual features into a text feature space and then generate features containing the abstract information that is hard to capture with visual prototypes and the detailed prototype information that is difficult to describe in text, enhancing the object-level visual-language model's counting capabilities. Additionally, RT-Counter incorporates our Weaving Transformer (Weaformer) layers, maintaining high descriptive power at a fraction of the computational cost. The Weaformer layer adopts a novel hybrid attention mechanism that can efficiently weave together local and global visual features. Extensive experiments on three public datasets show that RT-Counter successfully breaks the accuracy-speed trade-off in TOOC. While achieving a competitive MAE of 13.30 on FSC147, RT-Counter operates at 112.48 FPS, making it 7.4x faster and over 4$\times$ more parameter-efficient than the existing leading methods in TOOC. Our work aims at balancing high accuracy and real-time performance in TOOC. Code is available at: https://github.com/Jason-Mar1/RT-Counter.

05.
bioRxiv (Bioinfo) 2026-06-24

Statistical tests for bivariate spatial association across multi-omics data with disjoint coordinates

Spatial biology has entered a new era of multimodal profiling, with multiple, high-dimensional spatial omics types being measured on consecutive tissue slices, or co-assayed on the same slice. Interest then lies in statistical testing for spatial association between the features of the different modalities, to gain insight in biological processes. One major challenge is the multitude of bivariate combinations, leading to high computational demands. Another difficulty is the difference in spatial resolution between technologies, implying no one-to-one matching between the measurement spots of the two modalities, even after alignment. As a result, common statistical measures such as joint distributions and correlations are not defined, and tests need to rely on spatial vicinity only. Moreover, we argue that many existing bivariate association tests address an inappropriate null hypothesis, or make inappropriate assumptions, both implying absence of spatial autocorrelation in any of the features and leading to misleading conclusions. As a remedy, we modify tests for the detection of spatially variable genes (Moran's I, Gaussian processes and generalized additive models (splines)) to derive bivariate tests across modalities with non-overlapping coordinate sets and provide variance estimators that do account for spatial autocorrelation. We develop inference methods for single sections as well as for replicated experiments with multiple sections, and compare their performance in nonparametric and parametric simulations. Finally, we apply the newly developed methods to two co-assayed spatial transcriptomics and metabolomics datasets from mouse and human. The full suite of tests is available from github.com/sthawinke/sbivar as the R-package sbivar.

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

C2RM-Seg: Causal Counterfactual Reasoning with Structural-Semantic Priors for Weakly Supervised Histopathological Tissue Segmentation

Histopathological tissue segmentation is essential for computer-aided diagnosis, yet weakly supervised methods often suffer from noisy pseudo-labels generated by Class Activation Mapping (CAM). Existing CAM approaches tend to focus on staining-driven appearance cues rather than true causal tissue morphology, resulting in spurious localization and poor structural consistency. To address this issue, we propose C$^2$RM-Seg, a two-stage framework that integrates causal pseudo-label refinement with structure-aware semantic enhancement. For classification, we introduce a Causal Counterfactual Reasoning Module (C$^2$RM) that decomposes features into latent factors and performs counterfactual intervention via a learned causal structure matrix, suppressing confounding context and producing morphology-aligned CAMs. For segmentation, we design a Dual-Path Structural-Semantic Architecture that combines fine-grained structural features from ResNeSt with global semantic priors from a frozen DINOV3 foundation model. A cross-path gating mechanism adaptively regulates semantic injection using local structural cues to preserve boundary fidelity. To further mitigate residual pseudo-label noise, we propose an Uncertainty-Gated Margin (UGM) loss, which dynamically balances margin enforcement and confidence learning based on prediction uncertainty. Extensive experiments on two public histopathological tissue datasets show that C$^2$RM-Seg achieves state-of-the-art performance.

07.
arXiv (CS.CV) 2026-06-17

Bridging Modality Disconnect in Self-Reflection via Closed-Loop Visually Grounded Verification

In the era of Vision-Language Models (VLMs), enhancing multimodal reasoning capabilities remains a critical challenge, particularly in handling ambiguous or complex visual inputs, where initial inferences often lead to hallucinations or logic errors. Existing VLMs often produce plausible yet ungrounded answers, and even when prompted to "reflect", their corrections may remain detached from the image evidence. To address this, we propose the MIRROR framework for Multimodal Iterative Reasoning via Reflection On visual Regions. By embedding visual reflection as a core mechanism, MIRROR is formulated as a closed-loop process comprising draft, critique, region-based verification, and revision, which are repeated until the output is visually grounded. To facilitate training of this model, we construct **ReflectV**, a visual reflective dataset for multi-turn supervision that explicitly contains reflection triggers, region-based verification actions, and answer revision grounded in visual evidence. Experiments on both general vision-language benchmarks and representative vision-language reasoning benchmarks show that MIRROR improves correctness and reduces visual hallucinations, demonstrating the value of training reflection as an evidence-seeking, region-aware verification process rather than a purely textual revision step.

08.
arXiv (CS.AI) 2026-06-24

Deciphering Fingerprints of 3D Molecular Surfaces for Accurate Epitope Prediction

arXiv:2606.23830v1 Announce Type: cross Abstract: Molecular surfaces encode the geometric and physicochemical patterns that determine antibody-antigen recognition, central to epitope prediction. However, existing methods rely on sequences or backbone structures and struggle to capture discontinuous, surface-driven epitopes. This study presents SurfBind, a surface-centric learning framework for epitope prediction that operates directly on molecular surface representations. SurfBind integrates geometric and physicochemical cues through a Transformer-based architecture with patch-level surface modeling, binder-aware cross-attention, and a hierarchical coarse-to-fine prediction paradigm. Experiments on challenging epitope identification benchmarks, including SAbDab and DB5.5, demonstrate that SurfBind achieves state-of-the-art performance and strong generalization across unseen antibodies and conformational states, highlighting the value of interaction-aware surface modeling for understanding the crucial mechanisms of protein-protein interactions.

09.
arXiv (CS.LG) 2026-06-12

Scale Buys Interpolation, Structure Buys a Horizon: Certified Predictability for Equivariant World Models

作者:

arXiv:2606.13092v1 Announce Type: new Abstract: Scale buys interpolation; structure buys a certified horizon. A world model's average error says nothing about whether a particular prediction can be trusted, or for how long. For equivariant latent world models we give a computable, multi-step certificate of the predictable horizon: $T$-step rollout error is provably constant over each symmetry orbit (Theorem A) and stratified channel-by-channel by the predictor's Lyapunov spectrum, $T_j(\epsilon)\sim\log(1/\epsilon)/\lambda_j$. The horizon is two-sided – a matching lower bound makes approximate equivariance provably horizon-limited – and the certificate is exclusive to structure: orbit-constant error characterizes equivariance, so no non-equivariant model has it at any scale. Empirically, on 40-D Lorenz-96 only a $\mathbb{Z}_N$-equivariant network recovers the full Lyapunov spectrum ($R^2{=}0.98$); dense and recurrent baselines fail. Because the spectrum is faithful, the certificate acts, a priori: under a fixed sensing budget a $c\times$-inflated certificate provably needs $c\times$ the budget, and the equivariant certificate meets a budget its inflated dense counterpart cannot – with zero calibration data. The same read-out, unchanged, audits public pretrained world models training-free: TD-MPC2 checkpoints land on the certificate's own scope taxonomy – calibrated where strongly expansive (ratio 0.94-1.02), optimistic where weakly expansive, correctly abstaining where contracting – a map a deployed monitor replicates cell-by-cell, out-of-sample. Across the official 1M-317M multitask ladder, calibration does not improve with parameters. On V-JEPA 2-AC (1B, real robot data) the measured cross-check correctly overrides an over-promising tangent spectrum – the cross-validated audit, not the raw number, is the deployable object. Scale buys interpolation, not a calibrated horizon.

10.
arXiv (CS.CV) 2026-06-11

Q-Fold: Query-Aware Focus-Context Spatio-Temporal Folding for Long Video Understanding

Long-video understanding remains challenging for multimodal large language models, because temporally extended videos often contain thousands of frames and are therefore expensive to process exhaustively. Existing methods usually construct compact visual inputs from long videos under a limited visual budget. However, most of them still follow a frame-centric paradigm and apply similar representations to retained content regardless of its importance. This makes it difficult to preserve both high-fidelity visual evidence and broad temporal coverage. To address this issue, we propose Q-Fold, a training-free input construction framework for long-video understanding. Instead of treating isolated frames as the basic modeling unit, Q-Fold operates on contiguous temporal segments and constructs a heterogeneous Focus–Context representation under query guidance. Query-relevant segments are preserved as high-fidelity Focus Frames, while less relevant segments are folded into chronology-preserving contextual layouts. In this way, Q-Fold preserves critical visual evidence and broad temporal coverage, while better maintaining local temporal continuity within short segments. Experiments on four long-video benchmarks with multiple Video-MLLMs show that Q-Fold consistently improves performance without increasing the input budget. Notably, it achieves gains of up to 9.1 percentage points on an ultra-long video benchmark. Code will be made publicly available.

11.
arXiv (CS.AI) 2026-06-25

Offline Multi-agent Continual Cooperation via Skill Partition and Reuse

arXiv:2606.25389v1 Announce Type: new Abstract: Extracting skills from multi-agent offline dataset improves learning efficiency via sharing task-invariant coordination skills among tasks. In settings where tasks occur sequentially and the space of skills grows exponentially, existing approaches that rely on heuristically designed and fixed-sized skill libraries struggle to resolve the problem of distributional shift and interference, facing catastrophic forgetting and plasticity loss. To address this problem and endow agents with the ability to continually discover and reuse coordination skills in open-environment, we propose COMAD, a principled framework for Continual Offline Multi-agent Skill Discovery via Skill Partition and Reuse. We first discover skills from mixed multi-agent behavior data with an auto-encoder to transform coordination knowledge into reusable coordination skills. Then we construct a skill-augmented policy learning objective with multi-head architectures, explicitly guiding the advantage function with reusable skills identified via a density-based reusability estimator. Theoretical analysis shows our method approximates the optimum of a continual skill discovery problem. Empirical results across diverse MARL benchmarks show that COMAD continually expands its skill library to mitigate interference, achieving superior forward and backward transfer for task streams compared to multiple baselines.

12.
arXiv (quant-ph) 2026-06-15

Collision models for open quantum systems coupled to finite environments

arXiv:2606.14163v1 Announce Type: new Abstract: We study a system qubit repeatedly interacting with the same environmental qubit, with a reservoir acting on the environment between collisions via a completely positive, trace-preserving map. We show that complete suppression of system–environment correlations uniquely requires a full environmental reset, recovering a semi group dynamics with a time-independent Gorini–Kossakowski–Sudarshan–Lindblad generator, whereas a partial reset yields a continuous transition between Markovian and non-Markovian regimes governed by a single dimensionless relaxation parameter. For a resonant excitation-exchange interaction, we obtain exact closed-form expressions for the Bloch-vector dynamics for both a generalized depolarizing channel and a generalized amplitude-damping channel acting as the reservoir-induced map. Using the Breuer–Laine–Piilo measure and a Choi-matrix CP-divisibility witness, we identify three distinct dynamical regimes across the parameter space: CP-divisible Markovian dynamics, CP-indivisible but P-divisible dynamics, and non-P-divisible non-Markovian dynamics. The boundaries between these regimes, and the structural differences between uniform and anisotropic environmental relaxation, are characterized numerically.

13.
Science (Express) 2026-05-21

DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3′–guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

14.
arXiv (CS.CL) 2026-06-25

Weave of Formal Thought

Large language models (LLMs) attain remarkable surface fluency on code, yet they neither formally guarantee the syntactic validity of their output nor leverage the hierarchical structure defining the target language. While existing constrained-decoding frameworks address the former, they operate under rigid assumptions that preclude critical lexical mechanisms – including context-sensitive lexing, maximal-munch tokenization, and keyword extraction – and only approximate vocabulary masking, sacrificing completeness. For the latter, code LLMs typically inject grammatical structure via predetermined policies rather than learning which structural information to expose. In this work, we introduce Weave of Formal Thought (WoFT), a paradigm uniting rigorous syntactic validation with learned structural representations. First, we present a formal engine and constrained decoder that is sound and complete with respect to the full Tree-sitter specification. By augmenting generalized LR (GLR) parsing with a speculative-lexing construction that maintains concurrent lexer-state hypotheses synchronized with a GLR graph-structured stack, our decoder admits every subword token extending to a valid program prefix and rejects all others. Second, we present a latent-variable fine-tuning method training the language model to interleave non-terminal grammar symbols directly into generation. Utilizing the reweighted wake-sleep (RWS) algorithm to optimize the importance-weighted evidence lower bound (IW-ELBO) of the surface text, the model learns to selectively retain formal derivations as an adaptive structural scratchpad. For Python, fine-tuning StarCoder2-3B with our RWS objective reduces per-token cross-entropy by 14.3% relative to a text-only SFT baseline, demonstrating that discretionary latent syntax recovers critical structural information that flat autoregressive training discards.

15.
arXiv (CS.LG) 2026-06-19

Online Dynamic Batching with Formal Guarantees for LLM Training

arXiv:2606.19989v1 Announce Type: cross Abstract: Modern LLM training breaks a core assumption behind offline batch samplers: the true training cost of a sample is only observable after preprocessing, augmentation, templating, tokenization, and multimodal visual-token expansion. Unless one pays for a preprocessing- and augmentation-dependent length cache, batch construction is therefore blind to the quantity that determines padding, memory use, and GPU saturation. We introduce Online Dynamic Batching (ODB), a DataLoader-side drop-in system that moves batch formation to this point of accurate observability while preserving DDP step alignment. We formalize this synchronization requirement as the Distributed Group Alignment Problem and prove deadlock-free bounded termination with default join-mode identity coverage and opt-in non-join sample-quota closure. ODB requires no model, optimizer, or attention-kernel changes and is released as online-dynamic-batching with lightweight trainer adapters. Across public 2B/8B Qwen3-VL runs on UltraChat/LLaVA/ShareGPT4o, ODB improves literal emitted-sample throughput vs. fixed-batch Standard by 1.58-2.51x on single-node Full FT/LoRA and 1.71-3.78x on two-node Full FT, with Standard-comparable quality; production MM-Mix reaches 4.43x. Against GMT/BMT offline token-budget oracles, ODB is within 15% on UltraChat/LLaVA and faster on high-CV ShareGPT4o: 2.24-2.39x single-node Full FT/LoRA and 3.06-3.69x two-node Full FT. Together, ODB occupies the online/drop-in regime for high-heterogeneity LLM fine-tuning: large throughput gains at Standard-comparable quality, formal DGAP guarantees, and no length-cache precompute or kernel rewrites.

16.
arXiv (quant-ph) 2026-06-25

Estimating Fidelity to a Reference Quantum State

作者:

arXiv:2606.26034v1 Announce Type: new Abstract: We consider the problem of estimating the fidelity of an unknown quantum state to a known reference state to within additive error $\varepsilon$. We show that the sample complexity is $O(r^2/\varepsilon^2)$ with optimal $\varepsilon$-dependence when the reference state is of rank $r$, improving the previous best $O(r^2\log^2(1/\varepsilon)/\varepsilon^4)$ due to Utsumi, Nakata, Wang, and Takagi (QIP 2026). We also provide a lower bound of $\Omega(r/\varepsilon^2)$, improving the previous best $\Omega(r/\varepsilon+1/\varepsilon^2)$, with implications to quantum query complexity. Moreover, we further consider the case where the unknown state is of rank at most $r$ while the reference state can be arbitrary, for which the sample complexity is shown to be $O(r^2/\varepsilon^4)$. As an application, we present an approach to tolerant quantum state certification, generalizing the exact certification studied in B\u{a}descu, O'Donnell, and Wright (STOC 2019).

17.
bioRxiv (Bioinfo) 2026-06-24

trAIt: Species-by-Trait Data Retrieval using Large Language Models

Biological research often requires information about species' traits. Manual literature collation can be time-consuming and miss parts of the literature. To address this gap, we developed trAIt, a publicly available software for the retrieval of characteristics of species from scientific literature catalogued in the Europe PubMed Central (PubMed) database. trAIt provides a graphical user interface in which users specify species and characteristics of interest. Leveraging a large language model (LLM), trAIt retrieves relevant papers, combines their content through a consensus-based summarization model, and outputs a species-by-characteristic table. For a case study involving frog species, trAIt recovered 47.1% of trait-species combinations in 2.75 hours, while an expert curator independently recovered 62.4% over months. The consensus-based summarization substantially aids accuracy compared to single-source extraction. Across three case studies of vertebrate taxa, an expert confirmed the accuracy of 70.9% of trait-species entries recovered by trAIt. We observed considerable variation across taxa in trAIt's accuracy, which is possibly due to heterogeneity in open-access literature availability and inconsistencies in species and trait terminology. In sum, our analysis suggests that LLM-based tools can accelerate biological data synthesis but should be used to support domain experts' research, rather than replace their judgment.

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

TopBench: A Benchmark for Implicit Predictive Reasoning in Tabular Question Answering

Large Language Models (LLMs) have advanced Table Question Answering, where most queries can be answered by extracting information or simple aggregation. However, a common class of real-world queries is implicitly predictive, requiring the inference of unobserved answers from historical patterns rather than mere retrieval. These queries introduce two challenges: recognizing latent intent and reliable predictive reasoning over massive tables. To assess LLMs in such Tabular questiOn answering with implicit Prediction tasks, we introduce TopBench, a benchmark consisting of 779 samples across four sub-tasks, ranging from single-point prediction to decision making, treatment effect analysis, and complex filtering, requiring models to generate outputs spanning reasoning text and structured tables. We evaluate diverse models under both text-based and agentic workflows. Experiments reveal that current models often struggle with intent recognition, defaulting to just lookups. Deeper analysis identifies that accurate intent disambiguation serves as the prerequisite for leading these predictive behaviors. Furthermore, elevating the upper bound of prediction precision requires the integration of more sophisticated modeling or reasoning capabilities.

19.
arXiv (CS.LG) 2026-06-15

MOSIC: Model-Agnostic Optimal Subgroup Identification with Multi-Constraint for Improved Reliability

arXiv:2504.20908v3 Announce Type: replace Abstract: Current subgroup identification methods typically follow a two-step approach: first estimate conditional average treatment effects and then apply thresholding or rule-based procedures to define subgroups. While intuitive, this decoupled approach fails to incorporate key constraints essential for real-world clinical decision-making, such as subgroup size and propensity overlap. These constraints operate on fundamentally different axes than CATE estimation and are not naturally accommodated within existing frameworks, thereby limiting the practical applicability of these methods. We propose a unified optimization framework that directly solves the primal constrained optimization problem to identify optimal subgroups. Our key innovation is a reformulation of the constrained primal problem as an unconstrained differentiable min-max objective, solved via a gradient descent-ascent algorithm. We theoretically establish that our solution converges to a feasible and locally optimal solution. Unlike threshold-based CATE methods that apply constraints as post-hoc filters, our approach enforces them directly during optimization. The framework is model-agnostic, compatible with a wide range of CATE estimators, and extensible to additional constraints like cost limits or fairness criteria. Extensive experiments on synthetic and real-world datasets demonstrate its effectiveness in identifying high-benefit subgroups while maintaining better satisfaction of constraints.

20.
arXiv (CS.LG) 2026-06-24

KLip-PPO: A per-sample KL perspective on PPO-Clip

arXiv:2606.23932v1 Announce Type: new Abstract: Proximal Policy Optimization (PPO) is the standard policy-gradient algorithm for on-policy reinforcement learning. The literature presents it in two forms, a clipped surrogate that bounds the importance ratio between successive policies and a Kullback-Leibler penalty between them. These forms are treated as separate algorithms with their own gradients, their own hyperparameters, and their own reference implementations, and a sizeable body of empirical work compares them. We show that the gradient of the clipped surrogate is reproduced exactly by a Kullback-Leibler surrogate whose coefficient varies per sample, with closed-form dependence on the importance ratio and the advantage. The identity holds at every minibatch step and across the entire inner loop, and on five MuJoCo continuous-control benchmarks the two losses produce indistinguishable training curves. The reformulation exposes a structural feature of the clipped surrogate that the min notation hides. PPO-Clip's implicit per-sample penalty is a step function at the boundary of the trust region, and the shape of this coefficient is the natural design axis for generalising the algorithm. We sketch the resulting follow-up directions in the discussion.

21.
medRxiv (Medicine) 2026-06-19

Within-host pathogen population diversity predicts treatment response in tuberculosis

Background: Tuberculosis (TB) treatment outcomes remain suboptimal, and standard clinical diagnostics cannot reliably identify patients at high risk of treatment failure or relapse at the time of diagnosis. While within-host Mycobacterium tuberculosis genetic diversity is hypothesized to reflect the viable bacterial burden and adaptive capacity of the infection, its clinical prognostic value remains unknown. Methods: We conducted a prospective cohort study of 364 patients with newly diagnosed, rifampicin-susceptible pulmonary TB in South Africa. Patients received standard 6-month therapy and were monitored for up to two years to ascertain composite unfavorable outcomes (treatment failure, death, or relapse). To accurately detect low-frequency (unfixed) genetic variants and eliminate reference bias artifacts, we mapped medium to high depth short-read sequences against matched, patient-specific long-read assemblies. The association between baseline pathogen genetic diversity and clinical outcomes was evaluated using multivariable Cox proportional-hazards models. Results: After bioinformatic filtering, true unfixed variants were relatively rare but significantly enriched in genes mediating pathogen adaptation and drug tolerance, including transporter proteins and two-component regulatory systems. Within-host bacterial genetic diversity (i.e., the total number of unfixed variants) ranged from 0-20, with a median of 1 per patient. In survival analysis adjusting for known clinical risk factors–including HIV status, prior TB, baseline smear positivity, and radiographic lung involvement–baseline within-host genetic diversity emerged as a strong, independent predictor of unfavorable treatment outcomes. For patients with greater than 3 unfixed variants at diagnosis, each increase of 5 unfixed variants was associated with more than double the risk of a composite unfavorable outcome (adjusted Hazard Ratio, 2.36; 95% CI, 1.27 to 4.39; p=0.007). Conclusions: Baseline within-host pathogen genetic diversity is an independent predictor of unfavorable TB treatment outcomes. As sequencing becomes increasingly integrated into routine diagnostics, quantifying unfixed variants is an accessible approach that promises to risk-stratify patients and guide the duration of individualized regimens.

22.
medRxiv (Medicine) 2026-06-24

Reducing stillbirth in high burden settings using biomarkers and ultrasound technologies: protocol for the multi-centre prospective iTECH cohort study

Introduction Stillbirth prevention requires reliable detection of potential causes for timely interventions. Currently, there is no effective screening strategy to identify fetuses at risk of stillbirth. Prognostic models have been proposed as a potential solution, but there is a shortage of robust, clinically applicable models in low- and middle-income countries. Early birth is frequently initiated without proper risk stratification, leading to increased neonatal and infant morbidity and mortality. This study aims to develop and validate multi modal multivariable prediction models for stillbirth and pathologies that lead to stillbirth (preeclampsia & fetal growth restriction) using widely accessible and cost-effective markers. Stakeholder perspectives will also be assessed. Methods and analysis This multi-center prospective cohort study is running in four high volume regional referral hospitals in Uganda: Kawempe, Hoima, Lira, and Mbale. We will enroll at least 6,075 pregnant women attending routine antenatal care (ANC), above 13 years of age, and greater than or equal to11 weeks of gestation. Data and biological samples will be collected at 11-23 weeks, 35-37 weeks and at birth in all women. In a subset of women, additional measurements will be obtained between 24-34 weeks and 38-42 weeks to allow for spread of the data across the full spectrum of pregnancy. This data will enable us to investigate the physiological changes with gestational development in healthy or unhealthy pregnancies, to guide future monitoring and management of women and establishment of reference values for novel markers. The placenta will be collected for histopathological analysis in women diagnosed with intrauterine fetal demise at greater than or equal to 20 weeks of gestation, stillbirth nearmiss and their corresponding controls. Data on socio-demographics, obstetric history, current pregnancy conditions, and tests such as maternal hemodynamics, ultrasound, and biochemical markers will be collected from each participant, and used to develop regression and machine learning prediction models. Models will be validated and evaluated by comparing their calibration plots, precision and recall, F1 scores and accuracy, aiming for less complexity and reliable predictions. Emerging models will be translated into software as a medical device (SAMD), while taking into account user experiences, regulatory requirements, data pipelines in clinical workflows and user-friendly interfaces that facilitate access and the interpretation of outputs, to allow for seamless integration into existing electronic health information systems and decision support tools. To assess stakeholder perceptions, we will employ an exploratory qualitative component using focus group discussions, semi-structured and key informant interviews. The sample will include 81 purposively selected women and their partners who use maternity care services, local leaders and healthcare providers in and out of the four hospitals implementing iTECH in Uganda. Qualitative data will be audio recorded, transcribed verbatim and thematic analysis performed using Nvivo 12.

23.
bioRxiv (Bioinfo) 2026-06-10

Promera: a unified model for biomolecular structure prediction, filtering, and design

Generative models have become staple tools for modeling and designing biomolecular structures. However, although these tools have improved in structural prediction accuracy, their ability to filter designed binders—an essential use case—remains insufficient; whereas design methods have focused more on unconstrained binder generation rather than capabilities enabled by controllable design. We introduce Promera, a unified generative model that combines all-atom structure prediction with improved filtering and controllable design. We find that Promera's confidence metrics are more accurate for filtering binders from non-binders for both miniproteins and nanobodies, while its co-folding performance surpasses popular open-source models (OpenFold3-p2, Boltz-2) on therapeutically relevant categories. As a design model, Promera generates binders by predicting masked protein sequences with optional epitope, paratope, and template constraints. Remarkably, our nanobody designs match the in silico success rates from backprop-based techniques (mBER) when evaluated under co-folding confidence filters. We further provide two in silico demonstrations of the the versatile capabilities of our design method: epitope targeting of the Andes hantavirus glycoprotein with VHHs and active state stabilization of the beta-2 andrenergic GPCR. We conclude by proposing a scaling law for co-folding models, suggesting a path for further performance improvement.

24.
arXiv (CS.AI) 2026-06-16

RecourseBench: A Modular Framework for Reproducible Algorithmic Recourse Evaluation

arXiv:2606.16113v1 Announce Type: new Abstract: Algorithmic recourse methods provide counterfactual explanations that inform individuals of the actions required to overturn an unfavorable model decision. Despite rapid methodological progress, principled comparison remains elusive; existing frameworks are often difficult to extend and lack both interoperability and systematic verification that integrated methods faithfully reproduce their originally reported results. We introduce RecourseBench, a unified evaluation framework built around three commitments namely, modularity, reproducibility, and interactivity. The framework decomposes the pipeline into five fully decoupled layers – Data, Preprocessing, Model, Recourse Method, and Evaluation – governed by abstract interfaces and a dynamic registry. To address the reproducibility gap in prior benchmarks, we introduce a four-tier classification system in which every integrated method is validated by an automated test suite against its originally reported results. We further provide an interactive web interface for flexible, configuration-driven comparison across methods, datasets, and model architectures. Our framework currently integrates 28 state-of-the-art recourse methods and, to our knowledge, constitutes the first recourse benchmark to explicitly enforce method-level reproducibility through automated, quantitative testing.

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arXiv (CS.LG) 2026-06-25

KIGNet: Physics-Motivated Multi-Graph Representation Learning for Explainable Jet Tagging

arXiv:2512.07420v3 Announce Type: replace-cross Abstract: Jet identification plays a central role in analyzing data from high-energy collider experiments. While deep learning has improved jet classification, it often lacks interpretability. We introduce the Kinematic Interaction Graph Network (KIGNet), a graph neural network that integrates kinematic variables into jet classification by constructing four graph representations per jet, each weighted by a distinct variable: angular separation ($\Delta$), relative transverse momentum ($k_T$), momentum fraction ($z$), and invariant mass squared ($m^2$). Three of these ($\Delta$, $k_T$, $z$) are motivated by the Lund jet plane, grounded in perturbative QCD factorization; the fourth ($m^2$) adds complementary mass-scale sensitivity for heavy-flavor identification. Using Gradient-weighted Class Activation Mapping (Grad-CAM), we determine which variables dominate classification. Angular separation and relative transverse momentum account for about 76% of the total Grad-CAM attribution (40.72% and 35.67%), with momentum fraction and invariant mass contributing the remaining 24%. This hierarchy is consistent with the soft-collinear structure of QCD radiation in the training data, showing that the network learns physically interpretable representations rather than spurious correlations. On the JetClass dataset, KIGNet achieves a macro-accuracy of 95.07%, macro-AUC of 96.61%, and macro-AUPR of 81.52%, relative improvements of 2.45%, 3.40%, and 19.11% over the state-of-the-art baseline. On the Aspen Open Jets dataset of real CMS collision data, KIGNet produces substantially more structured latent representations than the baseline, reducing the Davies-Bouldin Index by 52.15% ($0.8395 \rightarrow 0.4017$) and increasing the Dunn Index by 42.33% ($0.0189 \rightarrow 0.0269$), confirming that physics-informed kinematic encoding generalizes beyond idealized simulation to experimental detector conditions.