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01.
arXiv (CS.AI) 2026-06-24

InSight: Self-Guided Skill Acquisition via Steerable VLAs

arXiv:2606.24884v1 Announce Type: cross Abstract: Vision-language-action (VLA) models can learn manipulation skills from demonstrations, but their capabilities are bounded by the skills in the training data. We present InSight, a framework that unlocks autonomous skill acquisition by rendering VLAs steerable at the primitive-action level (e.g., "move gripper to the bowl", "lift upward", "pour the bottle"). InSight consists of two primary stages: (1) an automated segmentation pipeline that partitions demonstrations into labeled primitives via VLM plan decomposition and end-effector poses to enable VLA primitive steerability, and (2) a VLM-guided data flywheel that identifies missing primitives required to accomplish a novel task, autonomously attempts demonstrations of the missing primitives with VLM-proposed low-level control, and automatically labels, stores, and integrates successful demonstrations into the VLA training set. We evaluate InSight across simulation and real-world manipulation tasks, including block flipping, drawer closing, sweeping, twisting, and pouring, without any human demonstrations of these target skills. Once learned, these primitives can be composed to execute novel, long-horizon tasks without additional human demonstrations. Our findings demonstrate that primitive steerability provides a practical foundation for continual skill acquisition in VLA policies. Project website: https://insight-vla.github.io.

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

Formal Verification of Learned Multi-Agent Communication Policies via Decision Tree Distillation

arXiv:2606.19632v1 Announce Type: cross Abstract: Multi-agent reinforcement learning (MARL) enables agents to develop coordination strategies through emergent communication, but neural policies lack the formal safety guarantees required for safety-critical robotic deployment in drone swarms and autonomous vehicle fleets. We present the first end-to-end framework for safety verification of learned multi-agent communication policies through policy abstraction: neural policies are distilled into interpretable decision trees, then formally verified, with empirical validation confirming that verified safety properties transfer to original networks. Our four-stage pipeline consists of domain-specific feature extraction from agent observations, decision tree distillation achieving 97.9% +/- 1.2% fidelity to neural policies, automated translation to PRISM probabilistic model checker specifications with complete feature-to-state-variable correspondence, and compositional verification of Probabilistic Computation Tree Logic (PCTL) properties via pairwise decomposition with union-bound aggregation and empirical neighbor modeling. Evaluating Vector-Quantized Variational Information Bottleneck (VQ-VIB) policies for multi-drone coordination with 5-7 agents, we verify 18 temporal logic properties across safety, liveness, and cooperation, achieving 88.9% property satisfaction with all five safety thresholds satisfied (0.3% collision probability vs. 1% threshold). Monte Carlo validation of original neural policies confirms that verified safety properties transfer with

03.
medRxiv (Medicine) 2026-06-16

Recurrence After Hepatic Hydatid Cyst Surgery: Scolicidal Agent Application Technique and the Effect of Cystopiliary Fistula

Objective: This study aimed to evaluate long-term outcomes in patients who underwent surgical treatment for hepatic hydatid cyst (HCC) disease and, in particular, to investigate the effect of scolicidal agent (SA) application method and the presence of cystobiliary fistula (CBF) on the development of recurrence. Materials and Methods: This single-center, retrospective study included 197 patients who underwent surgical treatment for HCC disease. Hypertonic saline was used as SA in all patients and was classified as intracystic or pericystic application according to the application method. The presence of CBF was evaluated according to intraoperative and postoperative findings. Patients were followed for 86 months, and the development of recurrence was identified by radiological methods. Comparisons were made between the groups with and without recurrence in terms of SA application method and the presence of CBF. Results: The median age of the patients was 38 years, and the median follow-up period was 86 months. SA application was performed into the cyst in 51.3% of the patients and around the cyst in 48.7%. The presence of CBF was detected in 49.7% of the patients. No statistically significant difference was found between the recurrent and non-recurrent groups in terms of SA application method (p = 0.344). Similarly, no significant relationship was found between the presence of CBF and the development of recurrence (p = 0.721). Conclusion: This study showed that the SA application method and the presence of CBF are not determinants of recurrence in HCC disease. It is thought that recurrence rates can be kept low with appropriate surgical technique and effective biliary tract management.

04.
bioRxiv (Bioinfo) 2026-06-19

FeatureMSEA: Metabolic Feature-based Metabolite Set Enrichment Analysis

Liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics detects thousands of metabolic features, but converting these chemical signals into metabolite set-level biological knowledge remains challenging. This is because most features lack unambiguous metabolite identities. Conventional metabolite set enrichment analysis (MSEA) generally requires identified metabolites and metabolite-level ranked inputs, leaving much of the untargeted feature space unused. Here, we present FeatureMSEA, a feature rank-based framework for metabolite set enrichment directly from metabolic features with ambiguous annotations. FeatureMSEA integrates multi-evidence feature-to-metabolite annotation, feature rank-based enrichment scoring, permutation-based inference, and iterative leading-edge-guided annotation refinement, with an optional LLM-assisted module for post-enrichment interpretation. In null comparisons of randomly split healthy samples, FeatureMSEA detected no significant metabolite sets, whereas metabolite-set spike-in simulations showed recovery of implanted signals. In a cerebrospinal fluid metabolomics study of Huntington's disease, FeatureMSEA identified dysregulated metabolite sets related to amino acid metabolism, mitochondrial energy metabolism, and neuroactive signaling. MS/MS-based annotation analysis further showed that FeatureMSEA refinement reduced annotation ambiguity and prioritized chemically consistent candidate metabolites. In summary, FeatureMSEA provides a general framework for extracting metabolite set-level biological insights from LC-MS untargeted metabolomics in which confident metabolite identification remains incomplete.

05.
medRxiv (Medicine) 2026-06-11

Polygenic risk scores associate with asthma phenotypes and proteomic analyses implicate IL1R1 in two family-based studies

Despite its high prevalence and the discovery of hundreds of genetic associations, the genetic determinants and heterogeneous manifestations of asthma remain incompletely understood. Incorporating polygenic risk scores (PRS) into asthma research offers a powerful approach to quantify inherited susceptibility, refine risk profiles, and advance mechanistic understanding of disease development. For this study, we leveraged whole-genome sequencing (WGS) data from two family-based cohorts of childhood asthma - the Genetics of Asthma in Costa Rica Study (GACRS) and the Childhood Asthma Management Program (CAMP) - to examine the transmission profiles of externally derived asthma PRS and their associations with clinical phenotypes in children with asthma. To further elucidate molecular mechanisms, we integrated large-scale external genome-wide association study (GWAS) summary statistics and genetic prediction models of protein abundance in a two-step proteome-wide association study (PWAS) of asthma. Our findings provide robust evidence supporting the validity of externally derived asthma PRS (asthma PRS association p-value p={10}^{-24} [GACRS and CAMP trios combined] for the Global Biobank Meta-analysis Initiative [GBMI]) and reveal consistent associations with spirometry measures and atopy markers across both studies, as 13 of 21 traits (62%) were significantly associated with the GBMI-PRS in the meta-analysis after multiple-testing correction. Moreover, the results of the integrative proteomic analysis implicate IL-1 signaling in the etiology of asthma, reinforcing the candidacy of IL1R1 antagonists for drug repurposing.

06.
arXiv (math.PR) 2026-06-11

Heat kernel estimates for Markov processes with blowing-up jump kernels

arXiv:2512.24807v2 Announce Type: replace Abstract: In this paper, we establish sharp two-sided heat kernel estimates for a large class of purely discontinuous symmetric Markov processes on closed subsets $F$ of $\mathbb{R}^d$, whose jump kernels blow up on a Borel subset $\Sigma$ of $F$. We assume that $F\setminus \Sigma$ is a $\kappa$-fat set and is dense in $F$. To the best of our knowledge, this is the first work establishing sharp heat kernel estimates for jump processes whose jump kernels blow up on part of the state space. The jump kernels under consideration take the form $J(x,y)=|x-y|^{-d-\alpha}{\mathcal B}(x,y)$, where $\alpha\in (0,2)$ and the function ${\mathcal B}(x,y)$ blows up at a subset $\Sigma$ of $F$. A fundamental obstacle is that the tails of the jump measures are not uniformly bounded, and hence standard techniques in heat kernel analysis do not provide a priori off-diagonal estimates. To overcome this difficulty, we develop a new approach based on weighted integral estimates for the heat kernel that are sensitive to both the blow-up behavior of the jump kernel and the geometry of $F\setminus \Sigma$. Examples of processes falling within our general framework include traces of isotropic $\alpha$-stable processes in $C^{1,\rm Dini}$ sets, processes in Lipschitz sets arising in connection with the nonlocal Neumann problem, and a large class of resurrected self-similar processes in the closed upper half-space.

07.
arXiv (CS.AI) 2026-06-24

Evaluating the Interpretability of Sparse Autoencoders with Concept Annotations

arXiv:2606.24716v1 Announce Type: cross Abstract: Sparse autoencoders (SAEs) are increasingly used to extract interpretable concepts from vision and vision language models, yet existing evaluation methods largely rely on proxy metrics or qualitative inspection rather than measuring semantic correspondence. We present a human-grounded evaluation framework that quantifies alignment between SAE latents and human-annotated concepts, without requiring user studies, and validate this matching through targeted attribute perturbations. To enable this intervention-style evaluation in vision, we construct synCUB and synCOCO, synthetic benchmarks of paired images that differ in exactly one attribute. We introduce Fully-Binary Matching Pursuit (FBMP), a coalition-based matching procedure that supports many-to-one mappings between SAE latents and annotated concepts, and consistently outperforms one-to-one baselines. For functional validation, we propose a Targeted Attribute Perturbation Alignment Score (TAPAScore), which tests whether matched concepts respond selectively and in the expected direction under targeted image-level attribute perturbations. Under sanity checks, our matching and TAPAScore are the only evaluated metrics that reliably distinguish trained SAEs from untrained ones. Across SAEs trained on CLIP and DINOv2 embeddings, we find that increased overcompleteness can reduce perturbation alignment, indicating a reduction in interpretability. Our evaluation framework suggests that moderate dictionary sizes provide the best trade-off, yielding the most interpretable SAEs. Code and datasets are available at https://github.com/JonasKlotz/sae-concept-eval.

08.
medRxiv (Medicine) 2026-06-17

Short-term relaxation after cervical rotatory manipulation is more closely associated with somatosensory input than cracking sound: a randomized controlled EEG study

Background Cervical rotatory manipulation is commonly used for neck-related symptoms and is often accompanied by a cracking sound. This sound is frequently regarded as a sign of successful manipulation, but whether it contributes substantially to the immediate relaxation response remains unclear. Objective This study examined whether short-term relaxation after cervical rotatory manipulation is more closely related to manipulation-associated sensory input than to the cracking sound cue alone. Methods In this single-session, three-arm, parallel randomized controlled study, 54 healthy volunteers were allocated to cervical rotatory manipulation, sham manipulation, or sham manipulation plus simulated cracking sound. Subjective outcomes were assessed before and after intervention, including positive affect, negative affect, comfort, and satisfaction. Eyes-closed resting-state electroencephalography was recorded before and after intervention. Prespecified neural outcomes included frontal alpha power, frontal alpha/beta ratio, occipital individual alpha frequency, and alpha-band fronto-parietal and fronto-temporal functional connectivity. Results Cervical rotatory manipulation produced greater improvements in positive affect, comfort, and satisfaction than sham manipulation or sham manipulation plus simulated cracking sound, whereas negative affect remained generally stable across groups. These subjective responses were accompanied by short-term electroencephalography changes, particularly in frontal alpha/beta and alpha-band fronto-parietal and fronto-temporal functional connectivity. Changes in frontal alpha/beta ratio were positively associated with changes in positive affect. In contrast, simulated cracking sound alone did not reproduce the full subjective or electroencephalography response observed after real manipulation. Conclusions The immediate relaxation response after cervical rotatory manipulation appears to be more closely related to manipulation-associated sensory input than to the cracking sound cue alone. These findings provide preliminary neurophysiological evidence for distinguishing real manipulation effects from sound-related contextual cues.

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

Persona-Pruner: Sculpting Lightweight Models for Role-Playing

Language Models (LMs) have shown remarkable potential as role-playing chatbots, delivering consistent, stylized interactions when given a specification of a character or user persona. However, applying these capabilities to real-world applications (e.g., ecosystems with numerous NPCs interacting simultaneously) exposes a critical inefficiency due to the excessive computational cost. In this paper, we question the necessity of dedicating a full, generalist model to a single persona, hypothesizing that a specific character identity relies on only a fraction of the model's total capacity. We observe that naively pruning LMs often severely degrades the role-playing performance for a specific persona; it does not distinguish between redundant knowledge and essential character traits. We propose Persona-Pruner, a framework that sculpts a lightweight role-playing model by isolating persona-specific sub-networks from a single description. Our experiments consistently show that Persona-Pruner preserves role-playing performance substantially more effectively than existing state-of-the-art LLM pruning techniques, reducing the performance drop from the dense model by up to 93.8% over the strongest baseline on RoleBench in LLM-as-a-judge score, while still maintaining general LLM capabilities. Code is available at https://github.com/jsu-kim/Persona-Pruner.

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

Quantifying mandibular positioning error and simulated temporomandibular joint-space changes in patient-specific occlusal splints

Patient-specific occlusal positioning splints can be regarded as physical realisations of planned mandibular transformations. However, the achieved mandibular pose may differ from the planned one because of acquisition, registration, fabrication, and positioning errors. This study presents a transformation-based biomedical engineering framework for quantifying mandibular positioning accuracy and propagating the resulting error to a simulated temporomandibular joint configuration. Multimodal 3D data, including CBCT, facial motion acquisition, and dental scans, were integrated in a common coordinate system. Positioning splints corresponding to selected mandibular poses were designed and fabricated, and their realised positions were evaluated using repeated scans of plaster models. Discrepancies between planned and achieved positions were represented as rigid-body error transformations and analysed in SE(3), together with surface-distance metrics. The estimated transformations were propagated to CBCT-derived TMJ structures to quantify changes in condyle-fossa distance maps. The results demonstrate a systematic translational component and anisotropic variability of mandibular positioning error, with measurable propagation to simulated TMJ-space changes. The proposed framework provides an objective method for documenting planned and achieved mandibular configurations and for analysing positioning uncertainty in patient-specific splint workflows.

11.
arXiv (CS.AI) 2026-06-18

Target-confidence Recourse Using tSeTlin machines: TRUST

arXiv:2606.18832v1 Announce Type: cross Abstract: Counterfactual explanations are widely used to provide algorithmic recourse in high-stakes decision-making systems. Most existing methods seek the smallest change to an input that flips a model's decision. However, decision-makers often rely not only on predicted labels but also on confidence thresholds and risk margins. Counterfactuals that barely cross a decision boundary can be fragile and unstable under noise or model variation. In this paper, we propose Target-confidence Recourse Using tSeTlin machines (TRUST), a framework in which users explicitly specify the desired prediction confidence for recourse. Rather than generating counterfactuals and evaluating confidence afterward, TRUST directly searches for minimal changes that satisfy a user-defined confidence target, enabling comparison of recourse options in terms of cost, confidence, and robustness. We instantiate TRUST using a Probabilistic Tsetlin Machine (PTM) combined with Bayesian optimization. The probabilistic clause-based structure of PTM links prediction confidence to the stability of decision rules. We show that counterfactuals satisfying the same rules can still differ substantially in reliability depending on how securely they satisfy those rules, revealing whether decisions are supported by robust or fragile clause activations. Experiments on synthetic and real-world datasets demonstrate that target-confidence counterfactuals produce more robust and interpretable recourse than conventional boundary-based approaches. Across multiple benchmarks, TRUST achieves perfect robustness while maintaining low recourse cost, including an L2 distance of 0.10 on the Haberman dataset at 0.92 confidence. By explicitly controlling confidence and exposing rule-level stability, TRUST provides actionable recourse for high-stakes decision support.

12.
bioRxiv (Bioinfo) 2026-06-14

Transposable elements as evolutionary substrates of proteindisorder in the human proteome

Intrinsically disordered regions (IDRs) are central contributors to protein function, evolution and human disease, yet the evolutionary routes that seed new disordered segments within pre-existing proteins are still poorly understood. Sequence insertions provide a powerful mechanism for disorder expansion, but the genomic donors of inserted IDR and its long-term conformational fate remain largely unknown. Transposable elements (TEs), abundant mobile genetic elements with distinctive compositional biases, represent compelling candidates for generating disorder within proteins. Here, we systematically mapped TE-derived segments across human proteins and isoforms, and we found that these insertions are strongly enriched in intrinsic disorder. The structural consequences of their insertion are shaped by TE class and family, reflecting the sequence biases of the elements from which they originate. Recent, Primate specific insertions preferentially generate disordered segments, whereas older insertions more frequently occupy ordered structural contexts, revealing an age-dependent transition in the conformational state of TE-derived sequences. TE-containing isoforms are expressed at lower levels than TE-free isoforms, particularly when insertions are young and disorder-rich, suggesting that intrinsic disorder may constrain the cellular tolerance of newly exonized sequences. These findings identify TEs as a major evolutionary mechanism linking genome mobility to the emergence of new disordered conformational ensembles in the human proteome.

13.
arXiv (CS.LG) 2026-06-18

Learning from Your Own Mistakes: Constructing Learnable Micro-Reflective Trajectories for Self-Distillation

arXiv:2606.18844v1 Announce Type: new Abstract: Self-distillation improves reasoning in large language models by using the model's own rollouts as training signal, typically through implicit logit-level alignment that minimizes KL divergence toward a privileged target distribution. However, because this supervision is generated via uncontrolled sampling, it provides no diagnostic insight into the model's specific errors or corrective guidance for its individual failure patterns. Consequently, the model learns to imitate a privileged distribution rather than receiving fine-grained corrections that pinpoint where and why its reasoning fails. In this paper, we propose Trajectory-Augmented Policy Optimization (TAPO), which advances self-distillation from implicit distributional alignment to explicit trajectory construction. During RL training, the model produces both correct and incorrect rollouts to the same query, and TAPO leverages this contrastive structure to construct micro-reflective corrections, new training trajectories that retain the model's erroneous reasoning up to the point of failure, then insert a natural-language diagnosis and corrected reasoning guided by a correct reference from the same sampling group. Since each trajectory is anchored in the learner's own prefix and solutions, the corrective signal preserves the model's on-policy distribution to a greater extent than the position-wise alignment imposed by KL-based methods. To integrate these trajectories, TAPO introduces difficulty-aware candidate selection at the model's capability boundary and decoupled advantage estimation to prevent gradient contamination. Experiments on AIME 2024, AIME 2025, and HMMT 2025 show that TAPO achieves consistent improvements over GRPO under the same number of training steps. Further analysis demonstrates that TAPO strengthens both first-pass reasoning and error-correction effectiveness.

14.
arXiv (CS.AI) 2026-06-15

FactoryLLM: A Safe and Open-Source AI Playground for Evaluating LLMs in Smart Factories

arXiv:2606.14119v1 Announce Type: new Abstract: Fault diagnostics and recovery in smart factories is challenging because critical information is dispersed across manuals of multiple machines which are interconnected through the manufacturing process. Large Language Models (LLMs) can provide a promising approach. In this paper, we propose FactoryLLM, a safe and open-source AI playground designed for evaluating different LLM-based retrieval-augmented generation (RAG) models by analysing documents from multiple machines across the manufacturing process. FactoryLLM enables the user to configure the LLM, and assess performance when reasoning over multiple documents, through a dual evaluation setup using both RAGAS and NVIDIA's LLM-as-a-Judge metrics. FactoryLLM is safe because it allows users to run local or open-source LLMs without sharing sensitive industrial data, providing a controlled environment for experimentation. We demonstrate the efficacy of FactoryLLM through a case study which involves an Autonomous Intelligent Vehicle and its Mobile Planner software, evaluating three LLMs across 30 maintenance queries derived from approximately 600 pages of cross-machine documentation. The results suggest that FactoryLLM is effective in cross-machine document reasoning: every model achieved a groundedness score above 0.88. The full code and documentation for community to test FactoryLLM with their manufacturing specific scenarios are publicly available.

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

PVminerLLM2: Improving Structured Extraction of Patient Voice via Preference Optimization

Motivation: Patient-generated text contains critical information on patients' lived experiences, social context, and care engagement, but remains largely unstructured, limiting its use in patient-centered outcomes research. Prior work introduced the PV-Miner benchmark and PVMinerLLM models for structured extraction. However, supervised fine-tuning (SFT) alone struggles with rare, fine-grained, and unevenly distributed errors, particularly in token-critical structured outputs. Results: We present PVminerLLM2, an improved set of LLMs for structured patient voice extraction that applies preference optimization to address token-critical errors beyond the reach of supervised fine-tuning. Our method introduces (i) a preference objective with token-level gated stabilization term that prevents degradation of absolute token likelihood under preference optimization, and (ii) confusion-aware preference pair construction to better capture low-separation distinctions. We further incorporate token-importance weighting and inverse-frequency reweighing to address token imbalance and class skew. Across multiple model sizes, PVMinerLLM2 consistently outperforms strong baselines, achieving gains of up to 4.43% (Code), 3.50% (Sub-code), and 1.55% (Span), and outperforms baseline LLM trained with existing preference optimization methods. Availability and Implementation: The supplementary material, code, evaluation scripts, and trained models for PVminerLLM2 are publicly available at: https://github.com/Data-Mining-Lab-Yale/PVminerLLM2

16.
medRxiv (Medicine) 2026-06-17

Adverse Childhood Experiences Reorganise the Brain-Personality Network Across the Psychosis Spectrum

Exposure to adverse childhood experiences is a pervasive risk factor for psychosis, exhibiting a linear relationship across the psychosis spectrum from subclinical schizotypal traits to schizophrenia spectrum disorders. While this association is often conceptualised within the vulnerability-stress framework, the systemic mechanisms through which childhood trauma reconfigures the brain-personality interactome remain poorly understood. We examined clinical, neuropsychological, and neuroimaging data from a sample of low- and high-schizotypy individuals, and patients with a diagnosis of schizophrenia spectrum disorder (N=120). Our aim was to map how trauma reconfigures interactions between neurobiology and schizotypal phenomenology. We adopted a mixed graphical model approach to jointly estimate conditional dependencies between childhood trauma, regional brain morphometry, and schizotypal traits across the psychosis spectrum. Our results show that childhood trauma reconfigures the brain-personality network, shifting it from a state driven by cognitive processes to one anchored in emotional (limbic) reactivity. This transition is marked by the increased influence of impulsive traits and a significant strengthening of connections within the salience network. These changes converge with a reduced thickness of the frontal executive regions, the brain's control centres, identified in our models. Collectively, our results suggest a structural phenomenological decoupling, where trauma conditioned affective circuits may bypass weakened top-down regulatory controls. These findings highlight the necessity of using integrative frameworks to capture how trauma fundamentally reshapes the relationship between the brain and schizotypal personality.

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

Projected random forests and conformal prediction of circular data

arXiv:2410.24145v3 Announce Type: replace-cross Abstract: We apply conformal prediction techniques to regression problems with circular responses, producing prediction sets with adaptive arc length and finite-sample coverage guarantees for any circular predictive model under the assumption of data exchangeability. Leveraging the high performance of existing predictive models designed for linear responses, we analyze a general projection procedure that converts any linear-response regression model into one suitable for circular responses. When random forests are used as base models in this projection procedure, we leverage the random forest out-of-bag mechanism to eliminate the need for a separate calibration sample in the construction of prediction sets. On synthetic and real datasets, the resulting projected random forest model produces more efficient out-of-bag conformal prediction sets, with shorter median arc length, than the split conformal prediction sets generated by two existing alternative models.

18.
medRxiv (Medicine) 2026-06-16

Presurgical immune biomarkers associated with pain intensity and pain interference recovery after total knee arthroplasty: findings from the PRIME-KNEE study

Chronic postsurgical pain (CPSP) prevalence after total knee arthroplasty (TKA) is >20%. Circulating immune biomarkers are known factors of musculoskeletal pain but poorly understood as CPSP predictors. This prospective, longitudinal study of 203 patients s/p TKA tested presurgical plasma biomarkers associated with 6-month CPSP, using promising approaches from geriatrics biomarker research: expected recovery differential (ERD; resilience outcome) and penalized, machine-learning regularization modeling (elastic net and LASSO regression). Forty-nine presurgical candidate biomarkers were considered. CPSP was operationalized using ERDs built around PROMIS pain intensity and pain interference, which quantified the difference between observed and expected recovery after accounting for demographic, comorbidity, reserve, and perioperative factors. Plasma/ERDs from ~130 patients revealed 13 biomarkers with the highest selection stability criteria, and either positive or negative (+/-) associations with ERDs. Interleukin (IL) 5 (-) and Lipopolysaccharide-Binding Protein (LBP; +) were associated with both ERDs. Unique associations with pain intensity ERD included Cytomegalovirus-Specific IgG Negative (CMV IGg-; -), Macrophage Inflammatory Protein-1 Beta (MIP1b; -), IL12p70 (-, Cluster of Differentiation 30 (sCD30;-), Interferon alpha 2a (IFN2a;+), and Leukemia Inhibitory Factor (LIF;+). Unique associations with pain interference ERD included Lipopolysaccharide (LPS;-), Activin A (-), IL8 (-), Serum Amyloid A (SAA;-), and IL7 (+). Protein-protein interaction analyses and topology motifs suggest a centralized network with higher-than-expected connectivity, involving IL5, IL7, IL8, MIP1{beta}, and IFN2a, among others. This study proposes rigorous yet feasible approaches to expedite pain biomarker research, and introduces presurgical biomarkers t0 consider in future TKA-CPSP biosignature derivation.

19.
bioRxiv (Bioinfo) 2026-06-22

Multivariate Random Forests for Cross-Modal Multi-Omics Integration

Multi-omics studies are widely used across many areas of biomedical research. In many diseases, some signals are shared across data types, while others are strongest in a single omics layer. Current multi-omics clustering methods often either merge all data types into a single representation, which can blur biology that is strong in one layer, or rely on linear structure that may miss more complex relationships across data types. We introduce multiRF, a random-forest-based method that handles complex data types and separates shared and modality-specific structure for multi-omics data. multiRF learns sample similarities across omics layers from multivariate random forests, combines them across data types, and uses the resulting weights to estimate the part of each omics layer that is predictable from the others. The remaining residual is treated as modality-specific signal, allowing shared and modality-specific similarities to be clustered separately. In simulations, multiRF recovered shared clusters as well as or better than established integrative methods while more reliably separating modality-specific signal under nonlinear data structures. In TCGA head and neck squamous cell carcinoma, the shared component aligned with the main subtype structure across established reference classifications, while gene- and miRNA-specific components revealed additional immune and developmental biology. In the ADNI cohort with matched blood DNA methylation and structural MRI, the shared cross-modal aging signal was associated with future conversion to mild cognitive impairment or Alzheimer's disease, and a DNAm-specific residual signal showed exploratory additional information. These results show that multiRF can recover a common disease axis while retaining biologically meaningful signals specific to one data type. multiRF is available as an open-source R package at https://github.com/novawz/multiRF.

20.
bioRxiv (Bioinfo) 2026-06-12

Computational Design of Optimal Sequences for Targeted Hypermutagenesis Using Recombination-Coupled Diversity-Generating Retroelements

Diversity-generating retroelements (DGRs) are natural systems that accelerate evolution via targeted hypermutation at adenines. We previously developed DGRec, a system combining DGRs and recombineering for programmable mutagenesis in Escherichia coli. We here address two important issues with DGRec: the dependence of mutagenesis efficiency on the dgrRNA secondary structure and the variability of the reverse-transcription biases with sequence context and position. First, we introduce and validate a method to recode non-functional templates, i.e. with low mutagenesis efficiency, into highly functional ones through synonymous mutations. Second, we develop a Long Short-Term Memory (LSTM) model to predict DGRec mutational profiles for any given template sequence. By integrating this LSTM model with our recoding method, we establish a comprehensive workflow for customized directed evolution, enabling researchers to precisely fine-tune DGRec in vivo mutagenesis to their engineering needs.

21.
arXiv (CS.CV) 2026-06-24

DivRL: Disentangled Self-Similarity Rewards for Diverse Subject-Driven Generation

Subject-driven image generation faces an "Identity-Diversity Paradox", where strong identity preservation often leads to rigid and low-diversity outputs. We propose a post-training framework called DivRL that jointly optimizes identity consistency and structural diversity simultaneously by leveraging disentangled visual features from a robust similarity model. Specifically, we introduce a Negative Self-Similarity Measure (nSSM) to quantify structural diversity, and Visual Semantic Matching (VSM) to evaluate identity consistency. We propose an "Explore-and-Suppress" strategy that treats VSM as a gated constraint: the model freely explores structurally diverse configurations, and only samples that violate the identity threshold are penalized via a quadratic hinge loss. This converts identity preservation from a competing objective into a feasibility constraint, allowing nSSM and VSM to improve jointly. Experiments demonstrate that our method effectively pushes the model to generate both consistent and diverse images and improves structural diversity while maintaining comparable identity consistency through a gated optimization formulation.

22.
arXiv (math.PR) 2026-06-17

Non-asymptotic Tail Bounds for the Kostlan–Shub–Smale Field: Tensor PCA and Spherical $k$-Spin Complexity

arXiv:2606.17665v1 Announce Type: cross Abstract: This paper builds a hierarchy of explicit, non-asymptotic tail bounds for the supremum of the Kostlan–Shub–Smale (KSS) random field on the sphere, and applies it to two problems: Spiked Tensor PCA and the landscape of the spherical $k$-spin model. For Tensor PCA, we study the non-asymptotic statistical limits of estimating a rank-$R$ symmetric signal tensor of order~$k\ge 3$ and dimension~$d\ge 3$ from a single Gaussian observation at signal-to-noise ratio~$\lambda$, through the profile maximum likelihood estimator, the MLE restricted to normalized rank-$R$ tensors of coherence at least~$\kappa$. Our analysis uses a single reduction: a deterministic geometric inequality (the Tube Method) and a rank-reduction step bound the estimation error by the supremum of the canonical KSS field, which the Kac–Rice formula turns into a Gaussian integral against the expected absolute characteristic polynomial of a shifted Gaussian Orthogonal Ensemble, controlled in turn by the four explicit tail bounds of our hierarchy (three from a Mehta–Fyodorov representation, one from a Ben Arous–Dembo–Guionnet large deviation). The same reduction yields two results, each with explicit constants. For estimation, a finite-$(k,d)$ error bound recovers the asymptotically optimal rate~$\sqrt{d\log k}$ of Perry, Wein and Bandeira, with explicit dependence on the rank~$R$ and the coherence~$\kappa$. For the landscape, a two-sided non-asymptotic bracketing of the annealed complexity of the spherical $k$-spin Hamiltonian recovers the Auffinger–Ben Arous–\v{C}ern\'y complexity function in the high-dimensional limit.

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

Bioacoustic Geolocation: Species Sounds as Geographic Signals

arXiv:2505.18726v3 Announce Type: replace-cross Abstract: Can we determine someone's geographic location solely from the sounds they hear? Are acoustic signals enough to localize within a country, state, or even city? In this work, we tackle the challenge of global-scale audio geolocation, with a particular focus on wildlife and natural sounds. We posit that bioacoustic signals contain informative geolocation cues because of well-defined geographic ranges of species. To test this hypothesis, we benchmark image geolocation and soundscape mapping methods, design oracles and species-centric baselines, and propose a hybrid approach that combines species range prediction with retrieval-based geolocation. We further ask whether geolocation improves with species-diverse recordings and spatiotemporal aggregation across neighboring samples. Finally, we extend our study to multimodal geolocation with case studies from movies that combine both audio and visual content. Our results highlight the potential of incorporating bioacoustic signals into geospatial tasks, motivating future work on species recognition and audio geolocation.

24.
arXiv (quant-ph) 2026-06-16

Towards Quantum Limited Spatial Resolution of NV-Diamond Magnetometry

arXiv:2508.13438v2 Announce Type: replace Abstract: Optically addressable ensembles of solid-state defects, such as nitrogen vacancy (NV) centers, are a leading modality for imaging-based magnetometry, thermometry and strain sensing. However, monitoring the fluorescence of individual defects within a sub-diffraction ensemble remains an outstanding challenge that currently limits access to atomic-scale features and dynamics. For compact clusters of NVs, we formulate imaging-based atomic sensing as a low-dimensional multiparameter estimation task in which one seeks to localize each defect and quantify the field strength in its immediate vicinity. In this work, we employ optical spatial mode demultiplexing (SPADE) to enhance localization and brightness estimation accuracy at sub-diffraction scales. Specifically, we develop a two-stage sensing protocol that augments direct imaging by projecting the incoming optical field onto point spread function (PSF)-adapted, i.e., PAD spatial modes and Yuen-Kennedy-Lax (YKL) spatial modes enabling efficient extraction of emitter positions and brightnesses. The YKL-SPADE measurement employed for brightness estimation is shown to be quantum-optimal in the case of two emitters and establishes a new connection between quantum detection and estimation theories. We numerically evaluate the statistical performance of our protocol for sub-diffraction optically detected magnetic resonance (ODMR) and Rabi sensing experiments. Compared to conventional focal plane intensity measurements, our protocol improves emitter localization accuracy by 6$\times$ and brightness estimation accuracy by 2$\times$ for tightly confined ensembles, residing well below the diffraction limit.

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arXiv (CS.AI) 2026-06-16

MiroBench: Benchmarking Realism in Agentic Simulation of Real-world Discussions

arXiv:2606.14715v1 Announce Type: cross Abstract: LLM agents are increasingly used to simulate real world interactions, but it remains unclear whether simulated behaviors preserve the content patterns and interaction dynamics of real human behaviors. Existing evaluations remain fragmented, which makes it difficult to compare systems or measure progress. In this paper, we focus on Reddit discussions as a concrete first step toward evaluating real-world social simulation. Reddit threads provide public, topic-grounded, multi-party interactions where people share experiences, debate, seek advice, express emotion, and collectively respond to products, events, and social issues. These discussions offer an observable window into broader social behavior, making them a useful setting for testing whether LLM agents can reproduce not only fluent text, but also the distributional patterns and interaction dynamics of real online communities. We introduce MiroBench, a benchmark for Reddit discussion simulation built from 4,292 real Reddit threads. MiroBench uses statistical tests to compare generated and real discussions across four major aspects: repetition and semantic uniformity, narrative content, toxicity and aggression, and structural complexity. Experiments across five domains and five models show that current simulators remain distributionally mismatched with real Reddit threads, while a lightweight prompt-based improvement procedure provides only limited gains. MiroBench offers a concrete benchmark for measuring, diagnosing, and improving realism in LLM-based social simulation.