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

MineExplorer: Evaluating Open-World Exploration of MLLM Agents in Minecraft

Multimodal large language models (MLLMs) have shown strong capabilities in perception, reasoning, and action generation. However, their ability to sustain exploration in dynamic open worlds remains unclear. Existing embodied and game-based benchmarks often compress interaction into short-horizon tasks or entangle success with domain-specific game mechanics. In this paper, we introduce MineExplorer benchmark for evaluating open-world exploration capabilities of MLLM agents in Minecraft. We first filter atomic tasks whose solutions rely heavily on Minecraft-specific knowledge to better reflect general open-world reasoning. Then we organize the benchmark around a ReAct-style capability formulation and compose atomic tasks into implicit multi-hop tasks. To further construct reliable instances, MineExplorer uses a multi-agent synthesis workflow that jointly designs task graphs, sandbox scenes, and rule-based milestone evaluators. Human evaluation shows that the multi-agent synthesis workflow produces significantly more reliable instances than a single-agent baseline. Experiments with advanced MLLM agents show that open-world exploration remains challenging, as strong models can handle many single-hop tasks but degrade sharply when hidden prerequisites must be coordinated over longer trajectories. Further analysis finds that task difficulty tracks agent completion, and larger models or thinking modes do not consistently translate into better performance. Code and dataset are available at https://github.com/Jometeorie/MineExplorer.

02.
medRxiv (Medicine) 2026-06-22

A Plasmodium vivax controlled human infection and transmission model to evaluate interventions across the life cycle

Background Plasmodium vivax is an underappreciated cause of malaria disease burden. No reproducible and standardized full life-cycle controlled human malaria infection (CHMI) model to accelerate development of novel interventions is available. Methods This transmission-CHMI trial was conducted in Nijmegen, Netherlands. Healthy, malaria-naive adults were sequentially enrolled into three cohorts of four and inoculated with the asexual blood-stage isolate PvW1. Primary endpoint was proportion of oocyst-positive laboratory-reared Anopheles stephensi mosquitoes. The sequential design allowed for adaptations between cohorts. At parasitemia >10 parasites/microL or symptom onset, participants received oral gametocyte-sparing treatment (GST): mepacrine (Cohort 1 and 3; 100 mg at 0, 8 16 hours, then once daily for 3 days) or piperaquine (Cohort 3; 480 mg single-dose). Transmission was assessed by direct skin feeding (DSF) and membrane feeding assay (DMFA) with and without enrichment of gametocytes. End-of-study treatment was atovaquone-proguanil (1000/400 mg once daily for 3 days). The trial was registered: NL-OMON57011. Findings Participants were enrolled between September 17, 2024 and March 25, 2025, all (12/12) developed parasitemia and transmitted PvW1 to mosquitoes. No serious adverse events occurred. Most adverse reactions were related to malaria. Mepacrine and piperaquine reduced asexual parasitemia while preserving gametocytemia and transmission. Peak transmission occurred within 3 days after GST and depended on the parasite developmental cycle, with highest gametocyte-infectivity ~48 h post ring-stage. In Cohort 3, mosquito infection reached 100% in all transmission assays. Median peak oocyst counts were 24 (IQR: 14-31) for DSF, 17 (12-19) for DMFA, and 150 (116-199) for enriched DMFA. A two-fold increase in pre-GST maximal parasitemia was associated with 20 additional oocysts (95% CI 8,6-32) in enriched DMFA. Sporozoites were viable in primary human hepatocytes. Interpretation A PvW1 transmission-CHMI is reproducible and safe, enabling P. vivax sporozoite production, relapse models and evaluation of transmission-blocking interventions.

03.
Nature Biotechnology 2026-06-23

Mapping and engineering the human cell–cell interactome

Efforts to systematically understand how cell interactions tune tissue-level function have motivated transformative advances in single-cell transcriptomics and spatial profiling. Although these technologies can measure molecular states in individual cells and their spatial mapping within tissues, they also reveal that there exists a fundamental knowledge gap of how cells influence each other in context. In this Perspective, we propose an initiative to map and engineer the human cell–cell interactome: a functional atlas of how all major human cell types communicate. We highlight how recent innovations can make this vision achievable. As a first moonshot, we propose the ‘Billion Cell×Cell Project’, which systematically characterizes the outcomes of defined cell–cell dyads across diverse cell types and conditions. We envision this multistage initiative will produce progressively deeper insights and unlock additional avenues for therapeutic discovery. We call on the scientific community to join us in building the tools, datasets and models that will decode and rewrite the language of life between cells. Di Carlo and colleagues discuss technologies required to map and engineer the human cell–cell interactome and the therapeutic avenues such an atlas could unlock.

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

LLM Parameters for Math Across Languages: Shared or Separate?

Large language models (LLMs) exhibit substantial cross-lingual variation in mathematical reasoning performance, but it remains unclear whether these differences reflect language-specific parameters or a shared mechanism that manifests differently by language. We present a cross-lingual mechanistic analysis of mathematical reasoning in LLMs, enabling us to localize and compare model parameters that support mathematical reasoning across languages. We find that the extracted math-associated parameters exhibit partial cross-lingual overlap, with the strongest overlap concentrated in intermediate model layers. We further observe that English consistently produces the largest set of math-relevant parameters, whereas lower-resource languages reveal smaller sets of relevant parameters. These results suggest that math-related behavior in multilingual LLMs is neither fully language-invariant nor fully language-specific, but instead exhibits partial cross-lingual parameter overlap with systematic language-dependent differences.

05.
arXiv (CS.CV) 2026-06-18

Physics-IQ Verified

Video generative models ( VGMs) have become a new frontier that can be used not just for video generation but for a multitude of downstream tasks, including world modeling. To advance these tasks, a good video model must understand the physical reality of the world. Evaluating this understanding is an emerging field and has led to the Physics-IQ benchmark, which quantifies this explicitly by comparing model-generated videos to real-world videos of physical experiments. In this work, we present a systematic audit of the Physics-IQ benchmark, expose shortcomings and propose three solutions that sharpen how we can measure physical understanding of VGMs. Specifically, we improve prompt and ground-truth quality to reduce the influence of confounding factors and further introduce a sample-level scoring system that weights each sample and metric equally. Our resulting benchmark, Physics-IQ Verified, refines 57.6\% of all samples and improves over 34.8\% of prompts. In a comparison study using six image-to-video generative models, we observe moderate but meaningful ranking changes (Kendall's $\tau = 0.46$). We hope Physics-IQ Verified advances the community by providing a more reliable signal toward physically accurate VGMs. The code for the benchmark can be accessed at https://github.com/google-deepmind/physics-iq-benchmark

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

Influence-Guided Concolic Testing of Transformer Robustness

arXiv:2509.23806v2 Announce Type: replace-cross Abstract: Concolic testing for neural networks alternates concrete execution with constraint solving to search for inputs that flip model decisions. We present a concolic tester for Transformer classifiers that uses SHAP estimates to rank pending path predicates by their impact on the current prediction. To support self-attention with multiple heads in execution backed by SMT solving, we implement attention semantics in pure Python that are compatible with the solver and make the softmax boundary explicit by concretizing exponentiation arguments. We evaluate our method on CIFAR-10 across three compact Transformer classifiers, ResNet18, and VGG16 under a one-pixel budget and a 900s horizon. Across the 500 model–input pairs in this matched comparison, our method achieves 60% success, compared with 15% for a differential evolution baseline that treats the model as a black box. In the primary two-layer Transformer branch-ordering study, SHAP-based predicate prioritization raises success from 56% to 60% and reduces median attack time by 51%. These results show that influence-guided path exploration can make concolic testing a practical way to find adversarial examples in Transformer models.

07.
medRxiv (Medicine) 2026-06-12

Integrative Mechanisms of Early Clinical and Research Training (ECART) in Orthopaedic Medical Education: A Qualitative Single-Case Study

Background: Early clinical exposure and student participation in research are important components of medical training. They may support learning motivation, evidence literacy, and self-directed learning. In many programmes, however, clinical training and research training remain separated. Few studies have explained, within a real teaching team, how learners turn clinical phenomena into researchable questions and how research participation can reshape their clinical understanding. Early Clinical and Research Training (ECART) is a clinical-research integration approach developed by an orthopaedic team at the Second Hospital of Shandong University. Methods: We conducted a theory-informed, interpretivist qualitative single-case study. The case was an orthopaedic clinical-research team at the Second Hospital of Shandong University. Participants included medical undergraduates, academic degree graduate students, professional degree graduate students, clinical teachers, and research platform leads. We used purposive sampling with maximum variation. Data were collected through semi-structured interviews and de-identified teaching documents. Data were analysed using the framework method and were interpreted with a Context-Activity-Mechanism-Outcome (CAMO) logic. Results: The analysis showed that ECART was not simply early entry into the clinic or early entry into the laboratory. It was a team-based learning process centred on real medical problems. Four themes were identified. First, early clinical exposure helped learners make real problems visible and nameable, rather than merely increasing exposure. Second, clinical-research connection followed different pathways. Professional degree graduate students often started from clinical uncertainties in residency training and case management, and moved toward evidence-informed small projects. Academic degree graduate students often started from literature gaps, experimental findings, and mechanistic hypotheses, and then used clinical feedback to calibrate meaning. Third, research training, through literature reading, group meetings, experimental design, data review, and mentor questioning, helped learners move from completing tasks to explaining problems. Fourth, sustained ECART depended on a tiered team ecology formed by clinical teachers, research mentors, research platforms, and senior peers. Based on these findings, we refined the ECART programme theory: real medical problems are translated through explanation, searching, experimentalisation, and feedback-based reinterpretation into research questions that learners can understand, discuss, and test. This process supports problem formation, evidence awareness, mechanistic reasoning, translational judgement, and career clarification. Conclusion: ECART is best understood as a clinical-research integrated learning ecology that emerges from real team practice, rather than as a fixed standardised course. Its educational value lies in a recurring cycle of real problems, research translation, multi-source feedback, and clinical reinterpretation. This framework may inform the design, evaluation, and contextual adaptation of clinical-research integration pathways in medical education.

08.
medRxiv (Medicine) 2026-06-10

A Three-Tier Operational Benchmark for Evaluating Large Language Models on Hospital Medication Safety

Objective. To introduce PsiBench, a clinically validated medication-safety benchmark for evaluating large language models (LLMs) against the standards used to certify hospital computerized provider order entry (CPOE) and electronic health record (EHR) systems, and a non-overlapping three-tier evaluation framework separating highest-stakes discrimination, the operational CDS regime, and category-correct alerting. Materials and Methods. PsiBench comprises 492 medication-safety scenarios across 11 safety categories, created by clinical pharmacology experts whose work underpins an annualized testing procedure used by more than 2,000 U.S. hospitals. The three-tier framework partitions the scenarios non-overlappingly: Discrimination (98 scenarios, 50 fatal vs 48 deception, near-balanced 51%/49%); Operational (394 scenarios, 261 serious unsafe plus 133 safe including 41 Excessive Alerts reclassified as operational negatives); and Attribution (311 alert-required scenarios). We evaluated 40 frontier LLMs from 10 providers over 3 runs per scenario at temperature 0.2 (or the provider default where temperature is not configurable), yielding 59,040 evaluations conducted April 21-23, 2026. Results. Headline binary performance on the full benchmark spans a wide range across the 40 models: F1 78.5%-92.3%, accuracy 65.4%-89.8%, sensitivity 81.4%-100.0%, specificity 6.1%-81.8%. Leading models by F1 (o4-mini 92.3%; o3 92.2%) pair high sensitivity with meaningful specificity; three models saturate sensitivity at 100% but fall below 25% specificity, indistinguishable from a naive always-alert classifier. The wide spread on a single headline metric motivates tier-specific analyses, developed in a separate clinical paper. Discussion and Conclusion. PsiBench and the three-tier framework operationalize a rigorous evaluation rubric for LLM medication safety, grounded in two decades of national hospital audit experience. The framework generalizes to any binary medication-safety classifier (rule-based, conventional ML, or LLM-driven), supporting tier-aware model selection and post-deployment surveillance.

09.
arXiv (CS.AI) 2026-06-16

Imperfect Visual Verification for Code Edition : A Case Study on TikZ

arXiv:2606.15693v1 Announce Type: cross Abstract: LLMs have significantly advanced code generation, enabling the synthesis of functional programs. While recent systems achieve strong performance on many coding benchmarks, tasks involving programs such as TikZ that generate visual artifacts remain challenging, in particular on visual code customization. Unlike generation from scratch, customization requires localized, semantics-preserving edits: the model must locate relevant code, modify it according to the instruction, and preserve the remaining structure and rendering. Approaches based on post-hoc iterative refinement/correction where a verifier provides feedback to guide corrections, have shown promise. However, in the case of programs with a visual outcome such as in TikZ, where correctness is harder or likely impossible to formalize and evaluate automatically, deterministic verifiers do not exist. Hence, developers can only rely on imperfect verifiers. In this paper, we conduct an empirical study to answer:to what extent can iterative refinement remain effective when the verifier itself is unreliable?} We use TikZ as a focused case study that isolates the core difficulties of the problem (weak code structure, fine-grained visual semantics, and difficult feature localization) in a controlled and challenging setting. We define visual code customization as an iterative editing problem with an imperfect oracle, and introduce a framework for analyzing such iterative refinements. We conduct a large-scale study and evaluate multiple LLM-based and tool-augmented visual verifiers within iterative refinement pipelines, and perform extensive manual annotation of refinement trajectories to assess verifier behavior and feedback quality. Our findings show that even imperfect verifiers can determine with moderate accuracy whether visual instructions are applied to code, achieving F1-scores up to 0.815. Feedback improves iterative refinement, especially for weaker models, adding 11–20 perfect customizations for Qwen3-vl-30b-a3b-Instruct, while stronger models like Gemini-3 gain fewer improvements (+5) but benefit more from accurate verification that prevents premature acceptance. Feedback is effective only when it precisely identifies image issues, provides actionable guidance, addresses all relevant problems, and remains grounded in the original instruction.

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

Spatially Selective Self-Training for Unsupervised Building Change Detection

Unsupervised building change detection aims to learn building-change masks from unlabeled bi-temporal remote sensing images. Existing label-free methods often follow a discrepancy-to-mask paradigm, directly using temporal differences, frozen foundation-model responses, prompt-based outputs, or post-processing results as final change maps. Although these strategies provide annotation-free cues, they do not learn a task-specific building-change detector and remain vulnerable to the gap between generic temporal discrepancies and building-defined structural changes. In practice, such discrepancies are often noisy and task-irrelevant, as appearance shifts, registration errors, and non-building modifications can produce strong but misleading responses. To address this problem, we propose SST-CD, a spatially selective self-training framework that reformulates fully label-free building change detection as end-to-end detector learning under noisy pseudo supervision. SST-CD uses temporal discrepancies as candidate pseudo labels and trains the detector only on spatially reliable pixels, whose reliability is estimated by a local consistency criterion that filters inconsistent regions from supervision. To further stabilize noisy self-training, a lightweight feature adapter recalibrates bi-temporal features, while a prototype-based decoder produces compact change and no-change representations. Experiments on LEVIR-CD, WHU-CD, and DSIFN-CD show that SST-CD achieves F1 scores of 83.08%, 91.69%, and 86.60%, respectively, outperforming existing unsupervised and label-free baselines.

11.
arXiv (CS.AI) 2026-06-15

Minim: Privacy-Aware Minimal View for Agents via Trusted Local Sanitization

arXiv:2606.13949v1 Announce Type: new Abstract: Modern LLM-powered autonomous agents increasingly rely on rich user interface (UI) state observations to achieve reliable action grounding in complex digital environments. However, many deployments transmit the full UI state to remote inference servers even when most elements are irrelevant to the current task, which can leak sensitive but unnecessary context such as authentication codes, private notifications, and background application states. We propose MINIM, a trusted local broker that performs privacy-aware minimization on the client side before any observation leaves the device. Grounded in Contextual Integrity (CI), MINIM learns a dual-score representation for each UI element by predicting an inherent sensitivity score (s) and a task-conditioned necessity score (n). These scores drive a ternary disclosure policy that keeps essential elements, abstracts sensitive attributes when needed, and removes task-irrelevant content. We optimize a CI-aware objective that penalizes necessity errors more strongly on high-risk content, enabling aggressive pruning while preserving task-critical information. Experiments on real-world UI observations derived from WebArena show that MINIM substantially reduces task-irrelevant sensitive leakage while preserving task-critical semantic context and the interactive affordances required for reliable agent actions.

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

Extensible Fluxonium Architecture Using Tunable Couplers with Low Shunt Capacitance

arXiv:2606.01647v2 Announce Type: replace Abstract: Fluxonium qubits have demonstrated high-fidelity operations and long coherence times in small-scale systems, highlighting their promise for quantum computing. However, large-scale integration into a high-performance two-dimensional (2D) qubit array remains the central challenge for practical applications. In this work, we introduce an extensible architecture for scaling up fluxonium qubits in 2D grids. To address the key challenges, namely achieving controllable strong interaction and high connectivity for qubits featuring small shunting capacitors (footprints), we propose using low-shunt-capacitance couplers to enable tunable interactions between fluxonium qubits. When embedded into 2D square lattices, large couplings can be achieved even with relatively small coupling capacitances, thus enabling multiple connections with sufficient capacitance budget. We further propose coupler realizations based on generalized flux qubit circuits, specifically the quarton and the fluxonium, and demonstrate that both enable fast, high-fidelity gates with low spectator errors, while supporting multiple connections on 2D grids.

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

VeriGraph: Towards Verifiable Data-Analytic Agents

LLM-based agents have demonstrated strong capabilities in data-intensive analytical tasks, yet their outputs are rarely verifiable: a reliance on linear text trajectories makes their reasoning difficult to audit. In particular, deterministic computations over raw data and semantic deductions over natural-language claims are often entangled in an unstructured stream, leaving numerical conclusions hard to reproduce and qualitative judgments hard to inspect. To address this, we propose VeriGraph, a traceable neuro-symbolic reasoning framework that enables agents to construct an explicit heterogeneous evidence directed acyclic graph (DAG) during execution. VeriGraph introduces three evidence-expansion primitives, namely computational, grounding, and derivational expansion, to connect raw data, interpreter variables, computed results, and natural-language claims in a unified graph. Under this formulation, structural traceability is reduced to graph reachability from raw data sources to terminal claims, while semantic support is measured by claim-level evidence evaluation. To improve graph construction, we further design a graph-based policy optimization strategy with a composite reward that jointly supervises answer correctness, computational integrity, and derivational coherence. Experiments on four benchmarks show that VeriGraph-8B achieves the highest overall score among all baselines. More importantly, VeriGraph produces auditable evidence graphs with substantially stronger claim grounding, achieving a 87.61\% Grounding Rate under our claim-level evidence support evaluation. These results suggest that explicit evidence-graph construction is a promising path toward verifiable data-analytic agents. Our code is available at https://github.com/ignorejjj/VeriGraph.

14.
arXiv (CS.CV) 2026-06-12

GEASS: Gated Evidence-Adaptive Selective Caption Trust for Vision-Language Models

Vision-Language Models (VLMs) hallucinate objects that are not present, and a growing line of work tries to curb this by feeding the model its own generated caption as auxiliary evidence – assuming that a caption, once available, is something to consume. We show this fails: naively appending a caption can lower accuracy rather than raise it, dropping Qwen2.5-VL-3B$^\dagger$ on HallusionBench by nearly ten points. To understand why, we build GD-Probe, a diagnostic set that pairs a global and a detail question on the same image, so that any difference in caption effect is attributable to the question alone. Caption utility proves to be a per-query property: the same caption helps global questions and harms detail ones, through a single mechanism – an embedded caption competes with the image for attention and pulls the model's evidence onto its own text – whose sign is set by whether the caption covers the queried content. Crucially, this regime is readable from quantities the decoder already emits, with no attention access or grounding. We turn this into GEASS (Gated Evidence-Adaptive Selective Caption Trust), a training-free, logit-level module that decides per query how much of the caption to trust, gating it by the clean path's confidence, weighting it by the entropy reduction it induces, and raising the evidence bar when the two pathways disagree. Across four VLMs and two benchmarks (POPE and HallusionBench), GEASS improves over both vanilla inference and contrastive decoding under a single fixed setting, adding only two forward passes and no parameters.

15.
medRxiv (Medicine) 2026-06-22

Maternal-Fetal immune networks and viral signatures in the healthy amniotic cavity

The intrauterine environment has traditionally been viewed as a privileged site protected by the placental barrier. However, emerging evidence suggests that early in utero microbial exposure may prime the developing fetal immune system. Here, using target-enriched metagenomics and high-dimensional proteomics, we characterized the intra-amniotic viral landscape and immune networks in 114 healthy pregnancies including both normal and anomalous fetuses. We identify a sparse yet heterogeneous human viral signature in 26% of samples, predominantly composed of Herpesviridae, Polyomaviridae, and Picornaviridae. Although viral reads abundance was associated with fetal abnormalities, viral detection generally did not induce overt inflammatory activation, supporting a state of immune homeostasis within the amniotic cavity. Instead, viral presence was associated with subtle and selective immune modulation, including altered inducible antimicrobial peptide expression (HBD-2 and HBD-3), coupled with an attenuation of regulatory cytokines. Our results further reveal that the amniotic immune environment is primarily governed by gestational age, transitioning from a Th1-predominant "alert" phase to innate-readiness preceding parturition. These findings suggest that fragments of viral genetic material within the amniotic cavity may contribute to fetal immune instruction without triggering overt inflammation, providing a foundational framework for understanding how "silent" viral-exposure during gestation influences the developmental origins of neonatal immunity.

16.
medRxiv (Medicine) 2026-06-19

Specific epigenetic age acceleration measures are associated with oral health outcomes in U.S. adults

Objectives: Oral health conditions impact a significant proportion of the global population. Chronological age is a known risk factor; however, characterization of epigenetic age remains limited and is expected to provide additional insight into biological mechanisms. Materials and Methods: The National Health and Nutrition Examination Survey (NHANES) was used to analyze the effect of epigenetic age measures of DunedinPoAm, and epigenetic age acceleration (EAA) of Horvath, Hannum, Weidner, Lin, VidalBralo, PhenoAge, GrimAge, and GrimAge2, on various oral health outcomes from survey and examination results. Univariable and multivariable logistic regression were performed, adjusting for sex, race-ethnicity, education, poverty income ratio categories, and dental insurance coverage status. Results: DunedinPoAm was associated with the last dental appointment being for an existing issue (p=0.0093), poor general oral condition (p=0.0226), limiting food due to teeth problems (p=0.0031), and recommendation to see a dentist within the next two weeks (p=0.0171). EAAs for PhenoAge, GrimAge, and GrimAge2, were associated with a smaller number of oral health outcomes, whereas EAAs for Horvath, Hannum, Weidner, Lin, and Vidal-Bralo showed no associations. Conclusions: In a representative U.S. population, DunedinPoAm was most consistently positively associated with different adverse oral health outcomes compared with other epigenetic aging measures. Tracking specific epigenetic ages such as DunedinPoAm, EAA GrimAge, EAA GrimAge2, and PhenoAge, may aid in additional monitoring of oral health outcomes. Understanding specific aging-related CpGs associated with oral health may aid in elucidating underlying molecular mechanisms.

17.
arXiv (math.PR) 2026-06-11

Convergence of a Critical Multitype Bellman–Harris Process with One Infinite-Mean Lifetime

arXiv:2606.11511v1 Announce Type: new Abstract: We study a critical multitype Bellman–Harris branching particle system in $\mathbb R^N$ with a finite type space $\mathbb K=\{1,\dots,K\}$. Particles of type $i$ move according to a symmetric $\alpha_i$-stable process and reproduce according to a critical offspring law whose mean matrix is irreducible and stochastic. The lifetime distribution of type $1$ is assumed to have infinite mean with regularly varying tail $$ 1-F_1(t)\sim c_1t^{-\gamma},\, 0 \frac{\gamma}{\beta}, $$ and a local increment condition on the heavy lifetime distribution, we prove convergence of the system to a Poisson random measure concentrated on the infinite-mean type.

18.
arXiv (quant-ph) 2026-06-24

Teleportation-based quantum state tomography

arXiv:2511.18621v2 Announce Type: replace Abstract: We explicitly show that the quantum teleportation protocol can be employed to completely reconstruct arbitrary two- and three-qubit density matrices. We also extend the present analysis to n-qubit density matrices. The only quantum resources needed to implement the teleportation-based quantum state tomography protocol are the ability to make Bell measurements and the ability to prepare a few different single qubit states to be teleported from Alice to Bob.

19.
bioRxiv (Bioinfo) 2026-06-23

Multi-Scale Machine Learning for Antibody-Antigen Binding Affinity Prediction Using Deep Mutational Scanning and Structural Features

Predicting how mutations alter antibody-antigen binding affinity is essential for antibody engineering and vaccine design, yet current methods generalize poorly to unseen complexes. We present a multi-scale machine learning framework integrating 93 descriptors across four modalities: physicochemical, structural, ESM-2 protein language model, and solvent-accessible surface area (SASA)/{Delta}{Delta}G_fold features. Under leave-one-complex-out deep mutational scanning (LOCO-DMS) cross-validation on AbAgym (36,541 mutations, 68 experiments, 13 pathogens), gradient boosting achieved MCC = 0.206; a confidence-stratified ensemble reached MCC = 0.374 (83.5% accuracy, 25.5% coverage). No single modality exceeds the majority baseline alone; only multi-scale fusion succeeds. Boltzmann ceiling analysis shows 45.9% of mutations are near-neutral (|{Delta}{Delta}G| < k_BT), bounding theoretical maximum MCC at 0.473; our method achieves 79.1% of this limit. Five deep learning architectures benchmarked under LOCO-DMS showed self-attention matching gradient boosting (MCC = 0.200). Cross-pathogen transfer failed systematically (mean 46.7%), confirming universal binding predictors remain an open challenge.

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

SoftSkill: Behavioral Compression for Contextual Adaptation

arXiv:2606.20333v1 Announce Type: new Abstract: Agent skills are commonly deployed as natural-language Markdown files that encode answer policies, evidence-use habits, and task procedures. These files are readable and portable, but they are consumed indirectly: for each task instance, a frozen language model must translate a long textual artifact into generation-time behavior. This paper asks whether a natural-language skill can instead initialize a compact continuous context object, refined by a trainable soft delta while the base model remains frozen. We propose SoftSkill, a frozen-backbone method that tunes such soft skills with next-token prediction and deploys them as latent behavioral priors at inference time. In our main single-round setting, a length-32 SoftSkill prefix on Qwen3.5-4B improves over no-skill prompting by 8.3 points on SearchQA, 42.1 points on LiveMath, and 1.3 points on DocVQA. Relative to SkillOpt, SoftSkill improves accuracy by 5.2 points on SearchQA and 12.5 points on LiveMath, while replacing hundreds to thousands of Markdown skill tokens with a few virtual tokens. We further study agentic execution as a harder boundary case, where sparse trajectory imitation provides useful signal but does not yet robustly compress long-horizon procedural behavior. More broadly, the results suggest that some task skills are better treated not as additional Markdown to be reinterpreted at inference time, but as compact latent controls over how a frozen model enters the task.

21.
arXiv (CS.CL) 2026-06-12

LLM-based Embeddings: Attention Values Encode Sentence Semantics Better Than Hidden States

Sentence representations are foundational to many Natural Language Processing (NLP) applications. While recent methods leverage Large Language Models (LLMs) to derive sentence representations, most rely on final-layer hidden states, which are optimized for next-token prediction and thus often fail to capture global, sentence-level semantics. This paper introduces a novel perspective, demonstrating that attention value vectors capture sentence semantics more effectively than hidden states. We propose Value Aggregation (VA), a simple method that pools token values across multiple layers and token indices. In a training-free setting, VA outperforms other LLM-based embeddings, even matches or surpasses the ensemble-based MetaEOL. Furthermore, we demonstrate that when paired with suitable prompts, the layer attention outputs can be interpreted as aligned weighted value vectors. Specifically, the attention scores of the last token function as the weights, while the output projection matrix ($W_O$) aligns these weighted value vectors with the common space of the LLM residual stream. This refined method, termed Aligned Weighted VA (AlignedWVA), achieves state-of-the-art performance among training-free LLM-based embeddings, outperforming the high-cost MetaEOL by a substantial margin. Finally, we highlight the potential of obtaining strong LLM embedding models through fine-tuning Value Aggregation.

22.
medRxiv (Medicine) 2026-06-18

Hospital staff views on the visibility, role and impact of Acute Learning Disability Liaison Services in Wales: a service evaluation

People with a learning disability experience marked health inequalities. In Wales, Acute Learning Disability Liaison Services (ALDLS) are delivered by specialised learning disability services, and all roles within them are undertaken by Learning Disability Liaison Nurses (LDLN). These services aim to enable access to, and delivery of, secondary care by supporting reasonable adjustments, facilitating communication, and coordinating care for people with learning disability during hospital encounters. However, independent evidence of the impact of ALDLS on patient care remains limited. This evaluation tries to address this evidence gap by examining hospital staff perceptions of the visibility, role, and impact of ALDLS across Welsh Health Boards, with the aim of informing service design and development and improving secondary care access and care for people with learning disability. The service evaluation used a qualitative approach involving interviews and a focus group with hospital staff across the seven Welsh Health Boards who had experience working with or interacting with ALDLS staff to care for patients with learning disability. Findings cover six key areas including i) visibility and delivery of ALDLS, ii) Barriers and challenges to effective ALDLS delivery, iii) Enablers of effective ALDLS delivery, iv) Positive impacts for patients with learning disability, v) Negative impacts and unintended consequences when the service is absent or limited, and vi) Participants recommendations for future improvements of ALDLS. To synthesise the findings, we developed an overview diagram, which illustrates how ALDLS may influence care quality in acute hospitals. The overview places the liaison service at the centre, showing how organisational enablers and barriers shape its delivery, and how its core functions support improvements in safety, timeliness, effectiveness, efficiency, equity, and patient-centred care. From the findings we have identified recommendations for practice and policy. These include that ALDLS should be recognised as a core, safety-critical component of acute hospital care for people with a learning disability, rather than an optional add-on. In practice, services should be more visibly embedded within routine pathways, with consistent site-based presence, clear referral criteria, early identification through electronic flagging and notification systems, and routine involvement in multidisciplinary planning for complex admissions and procedures. At policy level, ALDLS provision should be recognised within equality and patient safety frameworks as an essential service requiring sustained investment, national minimum configuration standards, adequate staffing, and better-integrated digital systems to support continuity, equitable access, and person-centred care.

23.
medRxiv (Medicine) 2026-06-22

AI-Assisted Longitudinal Analyses of Environmental and Psychosocial Determinants of Subjective Cognitive Difficulties

作者:

Short-term environmental exposures have been linked to cognitive and behavioral outcomes, although many reported associations may reflect broader geographic and contextual differences. Using longitudinal data from the All of Us Research Program (2018–2024), we linked daily weather and air-pollution exposures to repeated attention-related and subjective cognitive outcomes. Associations were evaluated using pooled, fixed-effects, lagged, and event-study analyses. Additional machine-learning analyses were conducted to explore potential heterogeneity and latent psychosocial structure. Replication analyses were performed using the 2024 Behavioral Risk Factor Surveillance System (BRFSS). Several environmental exposure measures showed small associations with cognitive outcomes in pooled analyses, but most attenuated substantially after accounting for within-location temporal variation. Mediation, sensitivity, and machine-learning analyses yielded similar conclusions. In contrast, mental-health burden, loneliness, and social functioning were consistently associated with subjective cognitive difficulty and exhibited substantially larger effect sizes than environmental exposures. Similar patterns were observed in BRFSS. Exploratory AI-assisted analyses yielded findings broadly consistent with the primary longitudinal analyses. These findings suggest that short-term environmental perturbations may have limited associations with cognitive outcomes after accounting for within-location variation, whereas psychosocial factors appear to be more consistently associated with subjective cognitive burden.

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

DifferAD-R1: A Difference-Guided IndustrialAnomaly Localization with Multimodal LargeLanguage Models

Industrial anomaly localization aims to accurately identify and localize abnormal regions in industrial products, addressing the critical challenge of detecting unseen defect categories in real-world scenarios. Traditional closed-set methods often suffer from poor cross-scenario generalization, while existingMultimodal Large Language Model (MLLM)-based approachesface two core limitations: they either adopt QA-style paradigmsmisaligned with the practical demands of localization, or relyon standard optimization techniques such as Group RelativePolicy Optimization (GRPO), which fails to deliver effectivelearning signals for subtle defects. To tackle these issues, thispaper proposes DifferAD-R1, an MLLM-augmented reinforcement learning framework tailored for industrial anomaly localization. We design a Difference-Guided dual-image paradigm,which reformulates the localization task as a one-shot difference grounding problem to effectively explore cross-scenarioanomalies. A Dual-Consistency Localization Reward is developedfor hard-to-detect anomalies, enhancing optimization stabilityand robustness. Additionally, we integrate a difficulty-awarestrategy with adaptive reweighting and group-wise resamplingto prioritize learning on challenging instances. To facilitateevaluations in real-world industrial settings, we construct theAD-DualDiff dataset, comprising 13K paired images across 20categories. Experimental results demonstrate that DifferADR1 significantly outperforms existing baselines and achievescompetitive performance compared to large-scale models likeQwen3-VL (235B parameters). Our code is publicly availableat: https://github.com/Rong2026/work-1.

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

3D-CBM: A Framework for Concept-Based Interpretability in Generative 3D Modeling

This research introduces a framework for incorporating Concept Bottleneck Models (CBMs) into 3D generative architectures to address the inherent 'semantic gap' in deep geometric learning. As deep models become central to 3D content creation, explainability shifts from a peripheral feature to a fundamental requirement for trust and accountability in safety-critical domains such as healthcare and manufacturing. CBMs provide an intrinsic interpretability solution by constraining latent representations to align with human-defined concepts, yet their application to unstructured 3D data remains largely unexplored. We design, implement, and validate a formal 3D-CBM architecture that maps raw geometric inputs, including point clouds and meshes, into a multi-tiered taxonomy of interpretable primitives and functional attributes. The framework further identifies strategic datasets, such as PartNet and ShapeNet, specialized for concept-based supervision. Experimental results from a 3D part-manipulation proof-of-concept experiment demonstrate the framework's efficacy, achieving a concept prediction accuracy of 88.8\% and a Chamfer Distance of 0.0115. Critically, the model enables precise test-time intervention, allowing for the interactive correction of structural errors. This work establishes a foundation for semantically-steerable 3D generation and invites further exploration into collaborative human-in-the-loop design systems.