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01.
bioRxiv (Bioinfo) 2026-06-19

Children's DNA Methylation and Family Dynamics in a Congo Basin Subsistence Community: Links with Parental Conflict and Fathers' Caregiving

Family environments may contribute to children's long-term health through biological processes, including epigenetic regulation such as DNA methylation (DNAm). However, most studies in this area focus on Euro-American populations while also rarely including fathering data. The current study investigated children's blood DNAm associations with positive (father caregiving) and negative (parental conflict) family dynamics in a smaller-scale subsistence society living in the Congo Basin rainforest. We measured DNAm from dried blood spots of 54 children (mean age=8.48 years) and conducted three epigenome-wide association studies aimed at discovering differential co-methylated regions (CMRs) associated with family dynamics. Via path models, we investigated the health implications and shared contribution of family factors of the identified CMRs. Differential DNAm associated with family dynamics was localized to genes related to stress, immunology, development, and aging, thus possibly linking to children's physical health and were simultaneously connected to other family factors such as number of siblings. Our findings suggested similarities in biological embedding of family factors across socio-ecologically diverse contexts.

02.
arXiv (CS.CV) 2026-06-19

Contour-Constrained Deformable Registration with Parameter Characterization for Head and Neck Surgical Guidance

With 890,000 annual new cases globally, head and neck squamous cell carcinoma has one of the highest recurrence rates among solid malignancies. Although frozen section analysis is the standard of care for intraoperative margin assessment, accurately relocating detected positive margins on the resection bed remains challenging due to imprecise alignment between resected specimens and their resection bed, compounded by post-resection mucosal tissue shrinkage. We present a biomechanics-driven deformable registration framework that corrects post-resection tissue deformation to provide intraoperative guidance. Our approach registers 3D specimen meshes to intraoperative resection bed point clouds using a deformable registration approach based on regularized Kelvinlet basis functions. The registration matches surface point clouds, fiducial landmarks, and boundary contour constraints that directly penalize perpendicular distance-to-agreement between specimen and resection bed boundaries. Across nine specimens from skin, buccal mucosa, and tongue sites, the overall mean target registration error was $11.11 \pm 4.07$ mm using rigid registration, which decreased to $8.20 \pm 2.68$ mm (26.19\% reduction) using deformable registration without contour constraint. The proposed contour-constrained deformable registration further reduced the error to $5.62 \pm 2.28$ mm, a 49.41\% reduction relative to rigid registration. We observed the largest reduction in the most clinically challenging tongue specimens. We also performed a systematic two-stage parameter search to characterize the relative importance of surface alignment, fiducial correspondences, contour constraint, and strain energy regularization. This search revealed that contour weighting dominates registration accuracy for tissue types with large lateral deformation, while the algorithm operates over a broad range of parameter combinations.

03.
medRxiv (Medicine) 2026-06-24

The role of Mediterranean diet adherence, smoking and their interactions in epigenetic age acceleration: A cross-sectional analysis of the Airwave cohort.

Background: Epigenetic clocks are markers of biological aging that may vary in their sensitivity to environmental stressors and lifestyle modifiers. To evaluate the utility of these biomarkers as sensors of the human exposome, we investigated how they respond to two powerful and opposing exposures: smoking, a source of oxidative stress, and the antioxidant-rich Mediterranean diet. Objectives: We assessed the sensitivity of eleven epigenetic clocks to diet and smoking and evaluated whether Mediterranean diet adherence modifies associations between smoking and epigenetic aging. Methods: We analysed 928 participants (mean age 41 years, 59% male) from the Airwave Health Monitoring Study. Linear regression models assessed associations between Mediterranean Diet Score (MDS) and epigenetic age acceleration (EAA), alongside smoking status and blood cotinine. Interaction terms between smoking status and MDS were included to detect dietary attenuation of smoking-related EAA. Models were adjusted for demographic, socioeconomic, lifestyle, and psychological covariates. Results: Higher MDS was associated with lower EAA for GrimAge ({beta} = -0.07 SD; 95% CI: -0.13, -0.01) and Bernabeu ({beta} = -0.08 SD; 95% CI: -0.14, -0.02) after false discovery rate correction. Smoking was strongly associated with increased EAA, particularly for GrimAge, Bernabeu, and DunedinPACE. Among current smokers, effect sizes were greater in those with lower dietary adherence (e.g. GrimAge: 1.79 SD, 95% CI: 1.54, 2.04) compared with those with higher adherence (1.35 SD, 95% CI: 1.01, 1.68; P_interaction < 0.001). Similar attenuation patterns were observed for Bernabeu. Higher intake of fruits, vegetables, and whole grains contributed most to the attenuation of smoking-related EAA. Conclusions: Our findings indicate that certain epigenetic clocks effectively capture the tension between harmful and protective exposures within the exposome. Rather than suggesting that diet neutralises the risks of tobacco, these results demonstrate that specific clocks are sensitive enough to monitor how lifestyle factors modify molecular responses to environmental toxins. This highlights the value of second-generation clocks in quantifying biological resilience.

04.
arXiv (CS.LG) 2026-06-18

A finite-element-inspired bipartite graph learned simulator for manufacturability assessment in large-deformation sheet forming

arXiv:2605.22845v2 Announce Type: replace-cross Abstract: Explicit dynamic finite element (FE) simulations are widely used for large deformation engineering analysis, but repeated simulations remain costly during design space exploration and optimisation. In explicit FE analysis, nodal kinematics and element level deformation measures evolve through coupled node element updates. This motivates graph learned simulators that approximate one step FE state transitions and roll them out autoregressively. However, many mesh based graph surrogates are node centred, which makes element level variables and native nodal elemental exchange less direct to represent. This work proposes CAttBiGNN, a cross attention based bipartite graph neural network for coupled nodal elemental learning. The graph represents FE mesh nodes and elements as distinct entities linked by directed node element edges, enabling nodal displacement increments and element level deformation states to be predicted on their native discretisation domains. An edge aware cross attention processor uses geometric edge embeddings to modulate directional node element message passing. For larger graphs, CAttBiUGNN combines the bipartite processor with graph downsampling and upsampling to improve long-range information propagation. The method is evaluated on dome shaped cold forming and corner shaped hot forming benchmarks. Comparisons with node centred baselines and bipartite and attention ablations show improved accuracy and balance in nodal displacement and elemental thinning prediction during autoregressive rollout. The results indicate that the proposed finite element inspired learned simulator can support manufacturability oriented field prediction and efficient design space exploration in large deformation sheet material forming.

05.
medRxiv (Medicine) 2026-06-23

Intrapartum Oxytocin and Maternal Outcomes Following Vaginal and Unscheduled Cesarean Delivery

Objective To examine whether intrapartum synthetic oxytocin exposure for labor induction or augmentation is associated with breastfeeding and postpartum depressive and traumatic stress symptoms. Methods We studied 1,296 postpartum women who delivered at a single tertiary care center, with assessments from the third trimester through approximately two months postpartum. Intrapartum oxytocin exposure was obtained from electronic medical records. Outcomes included exclusive breastfeeding, postpartum depression, and childbirth-related traumatic stress. Analyses were stratified by delivery mode and adjusted for key maternal and obstetric covariates. Results Overall, 63.3% of participants received intrapartum oxytocin. Among participants with vaginal delivery, oxytocin exposure was associated with lower exclusive breastfeeding at two months after adjustment (58.2% vs 70.3%; adjusted RR 0.86, 95% CI 0.76- 0.97; p = 0.02), but not with postpartum mental health outcomes. Among participants with unscheduled cesarean delivery, oxytocin exposure was independently associated with higher immediate postpartum depressive symptoms (F = 4.97, p = 0.03), acute childbirth-related stress (F = 4.56, p = 0.03), and two-month childbirth-related posttraumatic stress symptoms (F = 4.30, p = 0.04), but not two-month depressive symptoms. Conclusion Intrapartum oxytocin exposure was associated with lower exclusive breastfeeding after vaginal delivery and modestly higher childbirth-related distress after unscheduled cesarean delivery. These findings suggest that oxytocin exposure may mark or contribute to postpartum vulnerability in specific delivery contexts.

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

Priors Persist Through Suppression: A Stroop Paradigm for Lexical Override

作者:

Glossaries, technical specifications, and system prompts routinely ask language models to use familiar words in unfamiliar ways. When this works, the local rule does not install the new meaning on top of the old one; the pretrained prior keeps operating underneath, and its strength still shows through. We test this with a Stroop-style paradigm: a remapping rule (doctor means forest) pitted against the query word's lexical-prior distractor (hospital), with matched neutral controls. Across 11 open-weight models spanning four families and 1B-9B parameters, lexical-prior strength predicts interference even after item-level controls for answer prior, frequency, tokenization, and prompt wording. Activation patching on five aligned models locates a source-position triplet (definition subject, definition target, query word) that nearly fully recovers the conflict effect (aggregate $R \in [0.92, 1.06]$); a definition-target swap shows the triplet performs binding rather than identity matching. Dissociation experiments isolate target preservation as the binding-specific signature: distractor suppression occurs under matched, swap, and item-mismatched conditions alike, whereas target logit collapse occurs only when the definition-target position is corrupted. Behavior and mechanism converge on the same channel: the prior's strength both predicts which overrides fail and marks where the causal repair lands.

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

Beyond Scalar Distances: Semantic Attribute Gradients from Frozen MLLMs for Visual Embeddings

Vision encoders for retrieval are typically trained with class-label supervision: each training pair reduces to a scalar that uniformly pushes the embedding apart or pulls it together, as if every visual attribute either differed or matched. A multimodal large language model (MLLM), shown the same pair, can articulate those attributes and use them to predict whether the images share a class. We propose SAGA, a framework that turns this language-grounded, attribute-aware perception into a training signal for the encoder itself. Specifically, we use Group Relative Policy Optimization (GRPO) to reward the MLLM for correct predictions on the vision encoder's tokens. Since correct predictions require those tokens to expose the specific attributes that differ or match between the pair, the gradient pushes the encoder to encode them, replacing the uniform pair-level scalar with attribute-resolved supervision. An auxiliary attention-distillation loss anchors the encoder's embedding to tokens the MLLM attended to, and a standard metric-learning loss shapes the embedding geometry for nearest-neighbour retrieval. The MLLM is frozen throughout and discarded at inference, matching the deployment cost of a metric-learning baseline. SAGA improves Recall@1 by 3 to 6 points over state-of-the-art baselines on CUB-200-2011, Cars-196, FGVC-Aircraft, and iNaturalist Aves on zero-shot image retrieval.

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

Direction-Conditioned Policies via Compositional Subgoal Scoring for Online Goal-Conditioned Reinforcement Learning

arXiv:2606.16515v1 Announce Type: cross Abstract: Hamilton-Jacobi-Bellman theory implies that the optimal goal-conditioned action depends on the goal only through the gradient of the goal-reaching distance at the current state, yet standard online GCRL still conditions the actor on the raw goal – a signal that is geometrically uninformative when the goal is far from the data distribution. We propose Direction-Conditioned Policies (DCP), a fully online method that decomposes goal-reaching into two components sharing one InfoNCE representation $\psi$: a subgoal-scoring step that selects a visited state $z_t$ aligned with the final goal $g$ in $\psi_g$, and a direction-conditioned actor that consumes the unit direction $d_t$ and magnitude $r_t$ from $\psi(s_t)$ to $\psi(z_t)$. The two components train jointly, factor cleanly at deployment (subgoal scoring is removed, while direction conditioning remains with $g$ in place of $z_t$), and admit independent modification at the same $(d_t,r_t)$ interface. We prove three results. First, direction sufficiency under HJB: the optimal action under control-affine dynamics depends on the goal only through the value gradient. Second, a quantitative bound showing that, under mild conditions on the learned representation and assuming the scoring rule returns an on-path $z_t$, the actor's conditioning input at training and at deployment coincide up to representation error and geodesic slack. Third, a controllable-subspace characterization of when directional conditioning fails. Across nine environments, DCP improves over Contrastive RL on most final metrics, with the largest gains on manipulation and obstacle-interaction tasks; a qualitative analysis of the learned $\psi$-distance landscape shows the contrastive representation behaves as an online quasimetric encoding environment topology, and the single failure case (AntSoccer) localizes to a learned-gradient pathology that the theory anticipates.

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

The Culture Funnel: You Can't Align What isn't in the Data

Current cultural alignment approaches focus on inference-time interventions, assuming models already contain sufficient cultural knowledge. We argue modern LLM pipelines suffer from a cultural data funnel. Using a multidimensional tagging framework across pretraining, fine-tuning, alignment, and reasoning datasets, we show explicit cultural signals decline sharply during post-training, while geographically concentrated, task-specialized data dominates. Multilinguality enhances geographic diversity of cultural knowledge but does not ensure balanced representation. Our tags improve downstream cultural benchmark performance, demonstrating that advances require shifting focus in training data pipelines. To facilitate future research, we release our culturally tagged dataset with 5.6M samples at https://huggingface.co/datasets/CohereLabs/CultureMarkers.

10.
Nature (Science) 2026-06-10

Improved quantum processor logical error rates via correction and detection

作者:

Performing quantum algorithms for critical problems in physics and chemistry requires substantially lower error rates than the physical error rates of present quantum computers. Achieving such low logical error rates requires quantum error correction1,2 and physical error rates below a critical threshold value3–8. We experimentally demonstrate on a trapped-ion quantum charge-coupled device (QCCD)9,10 improvements in logical error rates ranging from 11× to 800× compared with several physical circuit baselines, including quantum computation on multiple qubits. Our results hinge on two quantum error correction code constructions optimized for an ion-trap processor: a 12-qubit code encoding two qubits inspired by Knill11 and a 16-qubit tesseract colour code encoding four qubits12,13. These constructions are combined with a scalable method of error detection and post-selection to achieve reduced logical error rates. Our results show that state-of-the-art quantum devices are already able to make use of fault tolerance and error correction to strongly suppress errors in non-trivial quantum circuit computations. Experimental demonstration of quantum error-correcting codes combined with error detection and post-selection applied to a trapped-ion quantum processor shows improvements in logical error rates ranging from 11× to 800× compared with several physical circuit baselines.

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

A Framework for Evaluating Agentic Skills at Scale

Agent skills – structured, reusable knowledge artifacts that augment LLM agent capabilities – have been rapidly adopted in industry, yet their cross-domain impact and use across commercial and open-source models remain under-studied, and no reusable methodology exists for evaluating an individual skill. In this work, we present an evaluation framework that lets a skill author construct realistic tasks to rigorously assess the aspects of a skill that matter most to them, and that estimates skill utility by solving those tasks. Further, we apply our evaluation approach at scale to 500 real-world skills, generating 1,000 tasks derived from the skills' content, along with instruction-following and goal-completion scoring rubrics. Using these metrics, we evaluate how 19 agent-model configurations, both proprietary and open-source, perform on the tasks. Our results show that models vary widely in how closely they adhere to the instructions encoded in skills, leading to substantial differences in their performance gains. Furthermore, we show that access to a skill significantly changes model behavior compared to the no-skill setup, providing an essential mechanism for encoding opinionated workflows into LLM agents. We release our evaluation dataset to support future work on agent skills.

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

When Does Language Matter? Multilingual Instructions Reveal Step-wise Language Sensitivity in Vision-Language-Action Models

Vision-Language-Action (VLA) models have shown strong performance in language-conditioned robotic manipulation, yet their robustness to linguistic variation remains poorly understood. In this work, we present the first systematic multilingual evaluation of VLA models by translating the LIBERO benchmark into ten languages, revealing severe performance degradation under non-English instructions, with success rates dropping by 30-50%. Through fine-grained analysis of task executions, we find that language influence is highly non-uniform across steps: certain steps exhibit strong language dependence and dominate overall task failure, while others are largely language-agnostic. Based on this insight, we propose a step-wise inference-time intervention that aligns representations according to step language sensitivity, substantially improving performance under linguistic variation. Our results indicate that language robustness in VLA models is fundamentally a step-wise control problem, highlighting the importance of temporally structured analysis for reliable embodied agents.

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

HoloRec: Holistic Encoding and Interleaved Reasoning for Generative Recommendation

arXiv:2606.15331v1 Announce Type: cross Abstract: Generative recommendation models that formulate the task as sequence generation overcome the objective fragmentation problem of traditional cascade architectures, yet existing approaches still suffer from flat semantic representations lacking hierarchical structure for multi-step reasoning and an externally constructed chain-of-thought (CoT) that requires expensive annotations and remains disconnected from the generation objective. We propose HoloRec, an endogenous chain-of-thought recommendation mechanism that unifies representation, reasoning, and generation by constructing a hierarchical semantic encoding matrix via multi-granularity nested residual quantization optimized by a holistic reconstruction loss. HoloRec supports two inference modes: a non-thinking mode that uses lightweight multi-granularity supervised alignment for fast prediction, and a thinking mode that employs an interleaved reasoning scheme to generate CoT steps on the fly, directly embedding reasoning into the generation process without external data. Experiments on multiple public recommendation datasets demonstrate that HoloRec consistently outperforms baselines, with especially significant gains in sparse scenarios, and the thinking mode achieves better accuracy than the non-thinking mode with only modest inference overhead.

14.
arXiv (quant-ph) 2026-06-15

Extending Covariant Fluctuation Theorems into Quantum Regime through Quasiprobability Approach

arXiv:2606.14519v1 Announce Type: cross Abstract: The covariant formulation of stochastic thermodynamics requires treating the stochastic work as a 4-vector, posing significant challenges for quantum systems due to the non-commutativity. We introduce a new quasiprobability distribution for the work 4-vector, which combines the Wigner and Margenau-Hill quasiprobabilities. This extends the covariant fluctuation theorems from classical to quantum regime. We illustrate our findings with a scalar field driven by classical particles with a generalized version of trace formula. Our work establishes a quasiprobability approach to studying relativistic quantum thermodynamics in a covariant way.

15.
arXiv (CS.CV) 2026-06-24

MambaRaw: Selective State Space Modeling for Efficient 4K Raw Image Reconstruction

In-camera JPEG previews are ubiquitous in raw image formats and provide an sRGB reference at negligible storage cost. Although existing metadata-based reconstruction frameworks can exploit this side information when recovering raw images, their context models often become computationally expensive especially at high resolution, eg, 4K raw image, given that attention mechanisms scale quadratically with feature maps, hindering its practical application. To address these limitations, we propose MambaRaw, a JPEG-conditioned metadata-based raw image reconstruction framework that uses State Space Models (SSMs) to estimate entropy parameters efficiently. Our key contribution comprises a Spatial-Energy Coupled Context Modeling mechanism with two lightweight modules: (1) TileMambaBlock, which performs Mamba-style selective scanning only on information-dense tiles to improve the efficiency; and (2) Energy-Aware Refinement (EAR), an identity-initialized residual module that enhance feature representation to match the long-tail energy distribution of raw signals. Extensive experiments on three camera datasets (Sony, Olympus, Samsung) show consistent improvements over strong metadata-based baselines and set a new state of the art for JPEG-guided raw reconstruction with great efficiency. Notably, at low metadata bitrates, MambaRaw increases PSNR by 1.2–1.4 dB and reduces end-to-end coding latency by about 9%. Code is released at https://github.com/Peizeli1/MambaRaw.

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

Quantum Annealing Enhanced Reinforcement Learning for Accurate Remaining Useful Lifetime Prediction

arXiv:2606.18503v1 Announce Type: new Abstract: Remaining useful life (RUL) estimation is central to predictive maintenance, where an unplanned failure can cost far more than the asset itself. Statistical degradation models miss the strong nonlinearity of real systems, and data-driven models often converge to suboptimal solutions in high-dimensional, non-convex search spaces. We propose a Quantum Annealing enhanced Q-Learning (QAQL) framework that couples the sampling behaviour of quantum annealing with the sequential decision making of Q-learning. Each Q-value update is encoded as a small quadratic unconstrained binary optimization (QUBO) whose ground state is the greedy action; rather than acting as a deterministic optimizer, the annealer returns a distribution over near-optimal actions across many reads, and this stochastic action selection supplies the exploration that curbs premature convergence on nonlinear degradation trajectories. The QUBO is solved on the D-Wave Advantage system using minor embedding, with the annealer woven into the reinforcement-learning loop rather than bolted on after training. We validate QAQL on two public benchmarks: the NASA C-MAPSS turbofan engine datasets and a device-fleet predictive maintenance dataset. Averaged over many independent runs and across six error metrics, QAQL outperforms the classical and quantum baselines considered in this study, with statistically significant improvements. The results indicate that quantum annealing is a usable, not merely theoretical, optimizer inside a reinforcement-learning loop for industrial predictive-maintenance applications.

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

Point-Identification of a Robust Predictor Under Latent Shift with Imperfect Proxies

arXiv:2603.15158v2 Announce Type: replace Abstract: Addressing the domain adaptation problem becomes more challenging when distribution shifts across domains stem from latent confounders that affect both covariates and outcomes. Existing proxy-based approaches that address latent shift rely on a strong completeness assumption to uniquely determine (point-identify) a robust predictor. Completeness requires that proxies have sufficient information about variations in latent confounders. For imperfect proxies the mapping from confounders to the space of proxy distributions is non-injective, and multiple latent confounder values can generate the same proxy distribution. This breaks the completeness assumption and observed data are consistent with multiple potential predictors (set-identified). To address this, we introduce latent equivalent classes (LECs). LECs are defined as groups of latent confounders that induce the same conditional proxy distribution. We show that point-identification for the robust predictor remains achievable as long as multiple domains differ sufficiently in how they mix proxy-induced LECs to form the robust predictor. This domain diversity condition is formalized as a cross-domain rank condition on the mixture weights, which is substantially weaker assumption than completeness. We introduce the Proximal Quasi-Bayesian Active learning (PQAL) framework, which actively queries a small, targeted set of diverse domains that satisfy this rank condition. PQAL can recover the point-identified predictor, demonstrates robustness to varying degrees of shift and outperforms previous methods on synthetic data and semi-synthetic dSprites, IHDP, ACS Folktables datasets.

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

Learning High Coverage Discriminative Parsimonious Rulesets

arXiv:2606.14156v1 Announce Type: cross Abstract: Learning systems based on IF-THEN rule representations readily offer interpretability, making them a crucial focus in contemporary AI research. A key objective for such rule sets is to achieve both high discriminative power and interpretability. While existing state-of-the-art algorithms implicitly prioritize predictive accuracy, they often fall short on one or more quality metrics that ensure interpretability, such as coverage and parsimony of rule sets. Motivated by this, this paper propose the development of CDPR, which aims to create highly accurate and interpretable rule sets for classification problems. To the best of our knowledge, this represents the first attempt to establish such an approach. In this study, we introduce two algorithms rooted in submodular maximization, which not only provide provable guarantees on coverage but also yield rule sets that are both discriminative and parsimonious. We empirically demonstrate that rule sets learned through our approaches achieve higher accuracy and interpretability and has more than a 2.5-fold improvement in average coverage rates when compared to the next best algorithm.

19.
arXiv (quant-ph) 2026-06-11

Towards the implementation of a quantum classifier

arXiv:2606.10150v2 Announce Type: replace Abstract: In this work, we investigate the use of a quantum circuit as a binary classification model in the context of quantum machine learning. We call this model, binary quantum classifier. First, we describe fundamental concepts of quantum computing and introduce the computational tool used: Qibo, an open-source framework for efficient quantum simulations and quantum hardware control. Then, we describe how to design a binary quantum classifier for the classification of images and small arrays of variables by showing how to input data in the circuit, defining a quantum circuit model Ansatz with trainable parameters and a loss function, and implementing multiple minimizers. We test our quantum classifier with two data sets. The first one is the MNIST data set which is composed of handwritten digits (reduced to only handwritten zeros and handwritten ones for binary classification). We study the behavior of different minimizers by increasing the number of layers of the Ansatz. The second data set represents two different high energy collisions that can occur at colliders such as LHC (CERN). Due to in-time proton-proton interactions known as pile-up, we distinguish two different data sets: "without pile-up" and "with pile-up". These collisions can be represented by images of size 32x32 or by six high-level variables that we call features. By increasing the size of the training data set and the number of layers of the Ansatz, we search for the best minimizer. Splitting the data set in training set and test set, we compute: ROC curve, AUC score, confusion matrices and test set accuracy. For "with pile-up" images, we compare the results obtained with the quantum classifier with a small convolutional neural network. We conclude that is possible to build a binary quantum classifier with a quantum circuit and we highlight its performances and limitations in comparison with classical technologies.

20.
medRxiv (Medicine) 2026-06-23

A pharmacometric grey zone reconciles high metronidazole resistance rates with bismuth quadruple therapy efficacy in Helicobacter pylori

Summary Background Metronidazole (MET) resistance in Helicobacter pylori (H. pylori) exceeds 50-60% globally, yet MET-containing bismuth quadruple therapy (BQT) achieves &gt90% eradication in MET-resistant infections. We hypothesise this discordance stems from a structural limitation of two-fold dilution: a pharmacometric grey zone between the 128 and 256 &microg/mL breakpoints where treatable isolates are systematically misclassified as high-level resistance. Methods In a real-world cohort of 4610 treatment-na&iumlve children (2019-2024), checkerboard assays determined the bismuth-MET synergy factor (SF). Population PK/PD modelling simulated gastric MET exposure (AUC

21.
arXiv (CS.AI) 2026-06-25

Supervised Post-training of Speech Foundation Models for Robust Adaptation in Speech Deepfake Detection

arXiv:2606.25328v1 Announce Type: cross Abstract: Large speech foundation models have shown strong potential for speech deepfake detection, but direct fine-tuning is limited by a mismatch between self-supervised pre-training objectives and spoof-specific artifacts. To address this, we propose a mix-frame post-training strategy to create localized spoof-oriented perturbations and use frame-level supervision to encourage the SSL model to learn local inconsistencies that are critical for robust spoof detection. On ASVspoof5, we achieve state-of-the-art EER 4.50% for a single model without data augmentation. On ASVspoof2021 LA/DF, it further achieves only 0.16\% absolute EER gap between LA and DF, indicating strong and balanced robustness across distinct distortion conditions. These results show that supervised post-training provides an effective and practical way to adapt speech foundation models for robust deepfake detection.

22.
bioRxiv (Bioinfo) 2026-06-11

Calibrated Uncertainty Quantification for Patient-Level AML Drug Sensitivity Prediction Using Split Conformal Prediction

Accurate prediction of ex vivo drug sensitivity in acute myeloid leukemia (AML) patients from transcriptomic data is a critical challenge for precision oncology. Existing computational approaches have explored uncertainty quantification in cancer drug response prediction primarily using cell line data, while patient-level AML models typically rely on heuristic confidence measures rather than statistically calibrated uncertainty estimates. Here, we present a framework applying split conformal prediction to patient-level AML drug response modeling using the BeatAML 2.0 cohort. We trained Elastic Net and XGBoost regressors on bulk RNA-seq gene expression profiles from 318 AML patients, analyzing 34,764 patient-drug observations across 122 compounds. Baseline models achieved median Pearson R values of 0.291 (Elastic Net) and 0.281 (XGBoost) across 122 drugs. Wrapping these models with split conformal prediction yielded well-calibrated prediction intervals across three confidence levels: empirical coverages of 81.4%, 90.7%, and 95.5% against nominal targets of 80%, 90%, and 95%, respectively. Analysis of prediction interval widths revealed substantial drug-class-specific uncertainty patterns, with HDAC and BCL-2 inhibitors exhibiting markedly higher uncertainty than MDM2 inhibitors, suggesting a potential association between transcriptomic predictability and drug mechanism of action, although several drug classes were represented by only a small number of compounds. Predictive uncertainty was not significantly associated with ELN2017 molecular risk classification (Kruskal-Wallis p=0.395) or NPM1 mutation status (p=0.788). These results demonstrate that statistically valid uncertainty quantification can be achieved for patient-level AML drug response prediction despite substantial biological heterogeneity. to the best of our knowledge, no published study has applied split conformal prediction to patient-level ex vivo drug sensitivity prediction in the BeatAML cohort, providing a principled alternative to heuristic confidence scoring approaches. Keywords: Acute myeloid leukemia (AML); Ex vivo drug sensitivity; Conformal prediction; Uncertainty quantification; Precision oncology; BeatAML; Transcriptomic biomarkers; Machine learning.

23.
arXiv (CS.CL) 2026-06-25

Scaling Laws for Agent Harnesses via Effective Feedback Compute

Agent harnesses shape language-model performance by controlling tool use, feedback, verification, memory, and repair. Yet raw test-time expenditure, such as tokens, tool calls, wall time, or cost, cannot distinguish useful feedback from redundant or unstable interaction. We introduce Effective Feedback Compute (EFC), a trace-level scaling coordinate for informative, valid, non-redundant, and retained feedback. We further define Estimated-EFC, NRS-EFC, harness efficiency $\eta$, and task-demand normalization for realistic traces and heterogeneous tasks. Across synthetic, real, held-out, and prospective evaluations, EFC-based coordinates outperform raw-compute baselines and SAS. Oracle-EFC/$D_{\mathrm{task}}$ reaches $R^2=0.99$ in controlled scaling, and NRS-EFC/$D_{\mathrm{task}}$ reaches $R^2=0.93$ on real traces where raw compute has near-zero or negative fit. Finally, \ours uses EFC as a companion control layer for existing harnesses, improving mean pass rate from $61.2\%$ to $68.2\%$ while reducing mean raw cost from $213.8$ to $85.1$ under matched settings. These results suggest that harness scaling depends on durable, task-sufficient feedback rather than raw computation alone.

24.
arXiv (CS.CV) 2026-06-19

Exploring Multi-Modal Large Language Models and Two-Stage Fine-Tuning for Fashion Image Retrieval

Composed image retrieval retrieves a target image using a composed query of a reference image and a modified text description. In the fashion domain, this task requires understanding subtle attribute variations such as color, pattern, and texture. However, existing approaches face limitations due to scarce annotated data and simplistic negative sampling. We propose a novel framework that integrates a multi-modal large language model (LLaVA) to generate attribute-aware triplets and introduces a two-stage fine-tuning strategy to enhance contrastive learning. We leverage pretrained vision-language models, such as CLIP-ViT/B32, to generate and concatenate sentence-level prompts with the relative caption and to scale the number of negatives using static representations. Experimental results demonstrate enhanced compositional reasoning and improved fine-grained retrieval behavior, underscoring the feasibility and potential of the proposed framework for fashion retrieval.

25.
arXiv (CS.CL) 2026-06-16

State-Grounded Multi-Agent Synthetic Data Generation for Tool-Augmented LLMs

Training tool-augmented LLM agents requires large corpora of multi-turn, tool-grounded conversational data that is expensive to annotate, privacy-constrained in production settings, and largely absent from public datasets. We present StateGen, a synthetic data generation platform that produces scored, reasoning-trace-rich training conversations by orchestrating a four-role LLM loop: a persona-conditioned user simulator, an agent under test, a state-grounded tool simulator, and a multi-axis LLM judge. The key architectural contribution is an authoritative state manager that maintains a structured world-state object across turns, enforcing a backend-is-truth invariant that eliminates the dominant class of tool-call hallucinations by construction. StateGen extends naturally to hierarchical multi-agent settings by declaring sub-agents as tools, all sharing a single state object. We report results on 64,698 evaluated conversations across three production corpora: tool-call hallucination scores reach 9.66/10, the system supports persona-driven variation via a 23-dimensional trait vector, and a cleanly separated train and golden evaluation set split confirms the data is not memorization bait (per-criterion gap analysis). Comparison with eight external systems shows that no single publicly available platform combines multi-turn generation, state-grounded tool simulation, hierarchical multi-agent support, and built-in judge scoring.