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

ADORE: Iterative Query Expansion with Retrieval-Grounded Relevance Feedback

LLM-based query expansion improves retrieval by enriching the original query with additional context. Yet most methods remain generation-driven, producing plausible pseudo-documents or expansions without checking how the target corpus responds. This can introduce retrieval drift, amplify misleading vocabulary, or miss terms that distinguish relevant from non-relevant documents. We argue that effective expansion requires retrieval-grounded feedback, not just single-pass generation or unverified iteration. We introduce ADORE (ADapt, Observe, Relevance Evaluate), an iterative framework that turns retrieval outcomes into feedback for the next expansion. At each round, an LLM generates pseudo-passages, a retriever exposes the corpus response, and a relevance assessor evaluates retrieved documents against the original query. These judgments identify what to reinforce, what remains undercovered, and what to suppress. Across TREC Deep Learning, BEIR, and BRIGHT, ADORE consistently outperforms strong query expansion baselines with notable improvements across nearly all evaluation settings, improving average nDCG@10 by 24.5% over BM25 and 3.6% over the strongest prior query expansion method on BEIR, and by 122.9% over BM25 and 9.2% over the best query expansion baseline on BRIGHT. Our code and data are publicly available.

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

APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization

arXiv:2606.12991v1 Announce Type: new Abstract: Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity. However, the de novo design of cyclic peptides remains challenging because methods must identify pocket-adaptive cyclization patterns and linkage sites while simultaneously controlling drug-relevant properties. This challenge is particularly pronounced for recent generative models trained predominantly on linear peptide data, which may fail to capture cyclization-specific constraints. To address the limitation, we introduce APCyc, a target-aware de novo cyclic peptide generation framework that explicitly models cyclization and jointly optimizes multiple essential physicochemical properties. By using an expanded residue vocabulary and explicitly encoding cyclization-site and linkage-type information, APCyc learns cyclization-aware representations and leverages Bayesian posterior guidance to steer sampling toward cyclic peptides satisfying multiple property objectives. Experimental results demonstrate that our model learns target-dependent cyclization preferences, and enables effective and controllable multi-property optimization for cyclic peptide design. The source code of this paper is available at https://github.com/HKUSTGZ-ML4Health-Lab/APCyc.

03.
arXiv (quant-ph) 2026-06-15

An integrated ultrahigh vacuum cluster tool for diamond surface science and single nitrogen-vacancy center measurements

arXiv:2606.13961v1 Announce Type: new Abstract: We present a custom-designed ultrahigh vacuum (UHV) cluster tool developed for studying shallow nitrogen-vacancy (NV) centers in diamond, enabling in situ diamond surface preparation, characterization, and single NV center dynamics measurements within a single connected platform. The system combines a surface science chamber for controlled surface modification and analysis with a cryogenic confocal microscope chamber dedicated to NV spin and optical measurements. This integrated approach enables a direct correlation between diamond surface chemistry and the resulting NV spin and charge properties. The instrument provides a versatile platform for systematic studies of surface-induced decoherence mechanisms and charge dynamics for shallow NV centers, and establishes a pathway toward reproducible surface engineering for quantum sensing applications.

04.
arXiv (quant-ph) 2026-06-15

Experimental violation of a Bell-like inequality for causal order

arXiv:2506.20516v2 Announce Type: replace Abstract: Quantum mechanics is compatible with scenarios where physical processes happen in an indefinite order. In theory, this feature could be detected through violations of inequalities on the observed correlations, analogous to Bell inequalities. However, experimental demonstrations of such violations have been missing until recently due to the complexity of the required setup. Here we report an experimental violation of a Bell-like inequality involving the correlations of four parties, one of which is spacelike separated from the others. Our demonstration employs 3 km fiber spools to simulate spacelike separation, and achieves high-speed operations in photonic time-bin encoding, nanosecond synchronization, and accurate temperature stabilization. These experimental advances enable a violation by 5.7 standard deviations and open a path towards a certification of indefinite order in conditions that guarantee spacelike separation with existing state-of-the-art devices. However, the certification is not device-independent, as it relies on knowledge about the setup to exclude bidirectional signaling–a loophole inherent to implementations in classical acyclic spacetimes, which may be resolved in future quantum-spacetime tests.

05.
Nature (Science) 2026-06-12

An innovative technology boosts image quality for protein structures

After years of effort, two research teams have developed ‘laser phase plate’ systems that could help cryo-electron-microscopy users to generate high-quality structures for a broad range of proteins. After years of effort, two research teams have developed ‘laser phase plate’ systems that could help cryo-electron-microscopy users to generate high-quality structures for a broad range of proteins.

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

Reinforcement Learning-Guided Retrieval with Soft Fusion for Robust Multimodal Imitation Learning under Missing Modalities

arXiv:2606.15514v1 Announce Type: cross Abstract: Robotic systems perceive the world through multiple input modalities – including visual camera streams and natural language instructions – and must select appropriate actions based on these signals. However, assuming the permanent availability of all input devices is unrealistic, as sensors may fail, become occluded, or drop out entirely during deployment. Robust handling of such missing-modality scenarios is therefore essential for real-world robot operation. This paper introduces RL4IL, a reinforcement learning guided method for imitation learning that selects the most suitable action for a given observation by identifying the most relevant expert demonstrations from a training library. A reinforcement learning policy, trained via Proximal Policy Optimisation over Breadth-First Search candidate sets, ranks candidate demonstrations and a soft cross-attention fusion head aggregates their action signals to produce the final prediction. When a modality is missing at inference time, a dedicated per-modality RL retrieval policy identifies donor demonstrations from the training library, and a soft imputation head reconstructs the missing embedding via cross-attention over the top-ranked donors – without requiring any retraining of the system. Experiments on three LIBERO benchmark suites demonstrate that RL4IL substantially outperforms state-of-the-art imitation learning methods under sensor dropout conditions, while requiring no policy network training. The code can be found at https://github.com/h-ismkhan/Reinforcement-Learning-via-kNN-for-Robotic-Learning-with-Missing-Camera

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

LoopCoder-v2: Only Loop Once for Efficient Test-Time Computation Scaling

arXiv:2606.18023v1 Announce Type: cross Abstract: Looped Transformers scale latent computation by repeatedly applying shared blocks, but sequential looping increases latency and KV-cache memory with the loop count. Parallel loop Transformers (PLT) alleviate this cost through cross-loop position offsets (CLP) and shared-KV gated sliding-window attention, making loop count a practical design choice. We therefore study PLT loop-count selection through a gain–cost view: an extra loop may refine representations, but CLP also introduces a positional mismatch at each loop boundary. We instantiate this study by training LoopCoder-v2, a family of 7B PLT coders with different loop counts, from scratch on 18T tokens, followed by matched instruction tuning and evaluation. Empirically, the two-loop variant delivers broad gains over the non-looped baseline across code generation, code reasoning, agentic software engineering, and tool-use benchmarks, improving SWE-bench Verified from 43.0 to 64.4 points and Multi-SWE from 14.0 to 31.0 points. In contrast, variants with three or more loops regress, revealing a strongly non-monotonic loop-count effect. Our diagnostics show that loop 2 provides the main productive refinement, while later loops yield diminishing, oscillatory updates and reduced representational diversity. Because the CLP-induced mismatch remains roughly fixed as refinement gains shrink, the offset cost increasingly dominates. This gain–cost trade-off explains PLT's saturation at two loops and provides diagnostics for loop-count selection.

08.
arXiv (CS.LG) 2026-06-18

Riemannian MeanFlow for One-Step Generation on Manifolds

arXiv:2603.10718v3 Announce Type: replace Abstract: Flow Matching enables simulation-free training of generative models on Riemannian manifolds, yet sampling typically still relies on numerically integrating a probability-flow ODE. We propose Riemannian MeanFlow (RMF), extending MeanFlow to manifold-valued generation where velocities lie in location-dependent tangent spaces. RMF defines an average-velocity field via parallel transport and derives a Riemannian MeanFlow identity that links average and instantaneous velocities for intrinsic supervision. We make this identity practical in a log-map tangent representation, avoiding trajectory simulation and heavy geometric computations. For stable optimization, we decompose the RMF objective into two terms and apply conflict-aware multi-task learning to mitigate gradient interference. RMF also supports conditional generation via classifier-free guidance. Experiments on spheres, tori, SO(3), and SE(3) demonstrate competitive one-step sampling with improved quality-efficiency trade-offs and substantially reduced sampling cost.

09.
bioRxiv (Bioinfo) 2026-06-24

Systematic benchmarking of multi-modal approaches for tumor-naive ctDNA detection and quantification

Longitudinal monitoring of circulating tumor DNA (ctDNA) has emerged as a promising framework for characterizing treatment response dynamics in cancer. Scalable tumor-naive approaches for quantifying ctDNA often involve whole-genome sequencing (WGS) or DNA methylation profiling, but their comparative performance and capacity for complementary integration remain poorly understood. Here we systematically benchmarked tumor-naive WGS- and methylation-based ctDNA quantification methods using plasma from 150 patients with colorectal, lung and breast cancer. Using paired high-depth WGS and EM-seq data, we generated 40,000 in silico samples and evaluated detection accuracy, limits of detection (LoD) and quantification (LoQ) across cancer types and sequencing depths (0.1x-30x). We further assessed single- and multimodal method combinations, identifying conditions under which integrated approaches enhance analytical performance for detection and quantification relative to single modalities. This benchmark delineates key performance trade-offs and provides a practical framework to support method development and guide future research applications in ctDNA-based biomarker studies.

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

To Intervene or Not: Guiding Inference-time Alignment with Probabilistic Model Blending

The wide deployment of LLMs has made model alignment necessary to make newly trained models safely and effectively respond to user instructions. Among different methods, inference-time alignment is often cheaper as it intervenes (i.e., offers guidances) only during output generation. Existing proposals apply guidances extracted from certain aligned models without properly assessing their reliability. Nonetheless, our systematic evaluation reveals that guidance effectiveness varies drastically across models; since ineffective guidances lead to further confusion and thus further interventions, the resulting excessive interventions typically indicate poor performance. To make interventions more effective and thus more efficient, we introduce BlendIn, an inference-time alignment framework that shifts from binary decisions to creating hybrid distributions integrating both models' knowledge. BlendIn stabilizes inference-time alignment by performing quality-aware alignment and proportionally weighting each model's contribution based on reliability. Compared with existing works, it preserves beneficial guidance while downweighting unreliable suggestions. BlendIn provides both diagnostic signals and mitigation strategies for misaligned guidance, achieving consistent and up to 50% performance improvement on challenging model pairs. Our code is available at: https://github.com/DecayingSeart/BlendIn.

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

FineDialFact: A benchmark for Fine-grained Dialogue Fact Verification

Large language models are known to produce hallucinations - factually incorrect or fabricated information - which poses significant challenges for many natural language processing applications, such as dialogue systems. As a result, detecting hallucinations has become a critical area of research. Current approaches to hallucination detection in dialogue systems primarily focus on verifying the factual consistency of generated responses. However, these responses often contain a mix of accurate, inaccurate or non-verifiable facts, making the use of a single factual label overly simplistic and coarse-grained. In this paper, we introduce a benchmark, FineDialFact, for fine-grained dialogue fact verification, which involves verifying atomic facts extracted from dialogue responses. To support this, we construct a dataset based on publicly available dialogue datasets and evaluate it using various baseline methods. Experimental results demonstrate that methods incorporating Chain-of-Thought reasoning can enhance performance in dialogue fact verification. Despite this, the best F1-score achieved on the HybriDialogue, an open-domain dialogue dataset, is only 0.74, indicating that the benchmark remains a challenging task for future research. We release our dataset and code at https://github.com/XiangyanChen/FineDialFact.

12.
arXiv (CS.CV) 2026-06-17

Detail++: Training-Free Detail Enhancer for Text-to-Image Diffusion Models

Recent advances in text-to-image (T2I) generation have led to impressive visual results. However, these models still face significant challenges when handling complex prompt, particularly those involving multiple subjects with distinct attributes. Inspired by the human drawing process, which first outlines the composition and then incrementally adds details, we propose Detail++, a training-free framework that introduces a novel Progressive Detail Injection (PDI) strategy to address this limitation. Specifically, we decompose a complex prompt into a sequence of simplified sub-prompts, guiding the generation process in stages. This staged generation leverages the inherent layout-controlling capacity of self-attention to first ensure global composition, followed by precise refinement. To achieve accurate binding between attributes and corresponding subjects, we exploit cross-attention mechanisms and further introduce a Centroid Alignment Loss at test time to reduce binding noise and enhance attribute consistency. Extensive experiments on T2I-CompBench and a newly constructed style composition benchmark demonstrate that Detail++ significantly outperforms existing methods, particularly in scenarios involving multiple objects and complex stylistic conditions.

13.
arXiv (CS.CL) 2026-06-15

Beyond Perplexity: UTF-8 Validity in Byte-aware Language Models

Byte-level tokenization enables language models to handle any Unicode input, but models can generate invalid UTF-8 sequences when encountering rare or unseen characters. We investigate the relationship between training scale and UTF-8 generation reliability with a 355M parameter model trained on 80B tokens from a balanced multilingual corpus of English, Japanese, Korean, and Chinese. We introduce multiple evaluation protocols that isolate UTF-8 structural validity from language modeling. UTF-8 validity convergence lags perplexity by a roughly a factor of two: perplexity stabilizes after 2.1B tokens, but UTF-8 validity requires 4.2B tokens. In context-free generation, rare characters achieve higher structural validity than common characters, suggesting over-specialization of frequent character representations. Through experiments, we observed that reliable UTF-8 generation is a distinct capability requiring evaluation beyond perplexity.

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

Adversarial Attacks Leverage Interference Between Features in Superposition

Why do adversarial examples exist, and why do they transfer between models? Existing explanations appeal to high-dimensional geometry, non-robust patterns in the input, and decision boundary structure, but none provides a representation-level mechanism that explains why specific perturbations succeed and why attacks transfer between models. In this paper, we show that adversarial vulnerability can stem from efficient information encoding in neural networks. Specifically, vulnerability can arise from superposition - the phenomenon where networks represent more concepts than they have dimensions, forcing non-orthogonal representation and thus interference. This interference causes perturbations targeting one representation to affect others, creating vulnerabilities determined by interference patterns. In synthetic settings with precisely controlled superposition, we establish that superposition suffices to create adversarial vulnerability. The resulting attacks are predictable: PGD-discovered perturbations align with theoretically optimal perturbations derived from the interference geometry. Models trained on similar data develop similar interference patterns, explaining attack transferability. We then show that successful attacks on image classifiers exhibit the structure predicted by our proposed mechanism. These findings reveal that adversarial vulnerability can be a byproduct of networks' representational compression, complementing existing explanations based on data properties or architectural factors.

15.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

16.
arXiv (CS.CL) 2026-06-19

What sentiment analysis can't see: Measuring whether customers were helped, and what went wrong, across 70,000 support conversations

Most companies read their customer support data at scale using sentiment analysis, which measures how customers sound rather than whether they were satisfied with the result. We tested a richer alternative on 70,450 support conversations from a leading online fundraising platform: alongside tone, we used GPT-5.4 to estimate each customer's satisfaction and to flag whether they reported a concrete problem, then validated all three readings against the 1-to-5 ratings customers left on the conversations they rated. The satisfaction estimate tracked those ratings far better than sentiment did, correlating at 0.47 against 0.36 and flagging unhappy customers with far fewer false alarms. The structured read also sees what sentiment cannot: tone and satisfaction disagree in 44% of conversations, a single "Neutral" label hides everything from quietly satisfied customers to ones who quietly gave up, and the largest group of all is "tolerated friction," customers who are satisfied but still reporting a fixable problem, a standing issue that no sentiment-based dashboard can surface. The broader finding is that LLM-based annotation can capture far more than the tonality of a customer's language, offering strong potential for new business metrics grounded instead in the customer's state (whether they were satisfied) and the cause of their problem extracted directly from the raw textual data of interactions and feedback.

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

SHIFT: Semantic Harmonization via Index-side Feature Transformation for Multilingual Information Retrieval

arXiv:2606.18801v1 Announce Type: cross Abstract: With the rapid expansion of massive multilingual corpora, Multilingual Information Retrieval (MLIR) has emerged as a critical technology for global information access. MLIR enables users to retrieve semantically relevant documents from multilingual text collections using a single-language query. However, recent multilingual dense retrieval models often exhibit a strong preference for documents in the same language as the query. This leads to severe language bias, where top-ranked results are dominated by documents of specific languages, even when documents in other languages contain more semantically relevant information. To address this issue, we propose SHIFT, a training-free method applicable in the indexing stage. Specifically, SHIFT utilizes parallel translation pairs to estimate a relative language vector for each target language with respect to a source language. Subsequently, SHIFT corrects the language-specific offset by subtracting this relative language vector from document embeddings during indexing. Our comprehensive evaluation across four MLIR benchmarks and diverse dense retrieval models confirms that SHIFT can effectively mitigate language bias and enhance MLIR performance.

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

Surrogate Assisted Pedestrian Protection Design via a Foundation Model Orchestrated Workflow

arXiv:2606.17577v1 Announce Type: new Abstract: AI-driven engineering workflows face particular challenges in crash safety design: unlike aerodynamics, crash events involve highly nonlinear contact dynamics, material nonlinearity, and discrete state transitions that are difficult to capture with data-driven surrogate models. To the best of our knowledge, we present the first foundation model–orchestrated workflow for crash safety design that enables surrogate-assisted exploration for pedestrian protection, reducing evaluation time from hours per CAE simulation to seconds. The workflow integrates four components: (1) a surrogate trained on CAE crash simulations to predict pedestrian leg injury metrics from design parameters, achieving an average $R^2=0.87$ and providing distribution-free conformal prediction intervals; (2) multiobjective evolutionary search (NSGA-II) to discover diverse feasible parameter sets under user-specified constraints; (3) a morphing-based geometry generator that maps parameters to topology-preserving 3D shapes; and (4) a natural-language interface in which an LLM orchestrates the workflow and a vision–language model supports semantic comparison of generated designs. In an automotive front-bumper case study, the workflow produces 35 distinct safety-compliant alternatives from a single exploration, a process that would require weeks with conventional CAE iteration. These results suggest that foundation models can serve as integration layers between ML surrogates and physics-based simulation, helping bring AI capabilities to safety-critical engineering domains.

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

Wisdom of Committee: Diverse Distillation from Large Foundation Models and Domain Experts

arXiv:2402.14035v4 Announce Type: replace-cross Abstract: Knowledge distillation from foundation models to compact domain models is challenging due to substantial gaps in capacity, architecture, and modality. For example, in our experiments, distilling from a 76M-parameter language model to a 2M-parameter recommender closes less than 40% of the performance gap between the undistilled student and the teacher. We show that introducing domain-specific experts – which share the student's architectural characteristics – alongside the foundation model as a diverse teacher committee significantly improves transfer. However, standard multi-teacher methods fail to exploit this diversity: naively combining heterogeneous teachers can degrade performance below single-teacher distillation. To address this, we propose DiverseDistill, an interactive distillation framework that employs a learnable Question-Answer mechanism to generate teacher-conditioned queries and align heterogeneous teacher outputs into the student's representation space. Unlike methods requiring gradient-based co-optimization or architectural modification of teachers, DiverseDistill operates with frozen teachers using only forward-pass inference through their intermediate layers: no parameter updates, no co-training, and no architectural surgery. A dynamic teacher importance mechanism further reduces training cost by filtering low-relevance teachers per sample (e.g., ~30% fewer forward passes with no quality loss for recommendation tasks), while the entire Distillation Module is discarded after training, adding zero inference overhead. Evaluations on recommendation (38x compression) and vision (3.6x compression) tasks demonstrate that DiverseDistill recovers 73-114% of the teacher-student performance gap, consistently outperforming all single- and multi-teacher baselines.

20.
Nature (Science) 2026-06-10

Whole-genome duplication shaped cell-type evolution in the vertebrate brain

作者:

The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show one-to-one homology with amphioxus. Moreover, ohnologues, particularly those from the first WGD, were more important than small-scale duplication paralogues for vertebrate cell-type evolution. To explore whether ohnologues are mechanistically important for this process, we predicted ancestral cell-type states and compared them to amphioxus and experimentally investigated macroglia. The findings indicate that ohnologues had a role in early vertebrate cell-type diversification. Moreover, by examining paralogue expression across cell types and species, we show that expression changes were mainly driven by dosage selection and subfunctionalization. We also link ohnologues to cellular diversity at different anatomical and cell-type scales. Our findings demonstrate the importance of WGDs for the evolution of early vertebrate brain complexity and highlight that the resultant ohnologues continued to capacitate cell-type evolution long after they were formed. Analyses of brain single-cell transcriptomes from human, mouse, lizard, lamprey and amphioxus reveal that duplicated genes (ohnologues) played a pivotal part in early vertebrate cell-type diversification.

21.
Nature (Science) 2026-06-22

Why heritage sites are at risk in a warming world — and how to save them

As rising seas and intensifying disasters threaten historic sites worldwide, new ways to understand, preserve and adapt these places are needed urgently. As rising seas and intensifying disasters threaten historic sites worldwide, new ways to understand, preserve and adapt these places are needed urgently.

22.
medRxiv (Medicine) 2026-06-12

Metastatic Patterns and Treatment Characteristics of Triple-Negative Breast Cancer in Nigeria: A Retrospective Cohort Study

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. It is associated with limited targeted treatment options, early relapse, and a high propensity for visceral metastasis. Data describing metastatic patterns and treatment characteristics of TNBC in Nigeria remain limited. Methods: This retrospective descriptive cohort study included 869 patients with TNBC managed at the Medserve-LUTH Cancer Center, Lagos University Teaching Hospital, Nigeria between June 2019 and June 2024. Demographic, clinicopathologic, metastatic, and treatment-related data were extracted from electronic medical records. Descriptive statistics were used to summarize patient characteristics, metastatic patterns, and treatment profiles. Associations between metastatic disease and selected clinicopathologic and treatment variables were explored using Pearsons chi-square test. Complete-case analysis was applied throughout. Results: The mean age at presentation was 52.09 {+/-} 12.26 years. Most patients were married (79.1%), postmenopausal (64.3%), and of Yoruba ethnicity (56.8%). Advanced disease predominated, with Stage III and Stage IV disease accounting for 42.9% and 35.6% of cases, respectively. Invasive ductal carcinoma was the most common histologic subtype (77.0%), while Grade II tumours constituted 51.3% of graded cases. Surgery was performed in 73.1% of patients, predominantly mastectomy (70.9% of surgical procedures). Chemotherapy was administered to 83.2% of patients, most commonly anthracycline-based regimens (41.8%), while radiotherapy was delivered to 63.5% of patients, with hypofractionated schedules of 42-43 Gy in 15-16 fractions accounting for 47.2% of radiotherapy courses. Metastatic disease was documented in 32.9% of evaluable patients. Lung metastasis was the most frequent site (62.5%), followed by bone (46.3%), regional lymph node invasion (38.5%), liver (23.0%), and brain (22.6%). Tumour grade and histologic subtype were not significantly associated with metastatic disease, whereas radiotherapy exposure demonstrated a significant association with metastatic status ({chi}{superscript 2} = 10.35, p = 0.001). Conclusion: TNBC in this Nigerian cohort was characterized by advanced-stage presentation, invasive ductal predominance, extensive use of multimodality treatment, and substantial visceral metastatic burden. Lung metastasis was the most common metastatic site. These findings provide contemporary real-world data on TNBC in Nigeria and highlight the continuing need for earlier diagnosis, timely referral, and sustained investment in comprehensive cancer care services.

23.
arXiv (CS.LG) 2026-06-12

Majority-of-Three is Optimal

arXiv:2606.13614v1 Announce Type: cross Abstract: We give a short proof that the majority vote of three independent consistent classifiers is an optimal learner in the realizable PAC setting. This proves optimality for the simplest voting scheme, while simplifying both the algorithmic structure and the probabilistic analysis of previous voting learners, including the algorithm of S. Hanneke and the analysis of bagging by K. Green Larsen.

24.
bioRxiv (Bioinfo) 2026-06-21

OracleScreen-LILRB4: Machine Learning-Guided Discovery of Myeloid Immune Checkpoint Binders Validated in Patient-Derived Cells

The identification of small molecule modulators of immune checkpoint proteins remains a significant challenge in drug discovery due to the flat, featureless nature of protein-protein interaction interfaces and the characteristically low hit rates observed in conventional high-throughput screening campaigns. Here we report OracleScreen-LILRB4, an ensemble machine learning framework trained on quantitative biophysical screening data from two structurally diverse compound libraries (19,800 compounds total) screened against the myeloid immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3). By formulating binding prediction as a regression task targeting continuous {Delta}Fnorm values rather than binary hit classifications, OracleScreen-LILRB4 achieved a mean Spearman R of 0.61 and ROC-AUC of 0.86 under scaffold-aware cross-validation. Prospective virtual screening of a 45,760-member compound library and experimental validation of the top 200 predictions yielded a 28.5% hit rate, representing a 15.0-fold enrichment over baseline, with 16 compounds demonstrating nanomolar-affinity LILRB4 (ILT3) engagement. Lead compounds ORS-22 and ORS-14 restored anti-tumor immune activity across patient-derived colorectal cancer and acute myeloid leukemia co-culture systems, reversing SCG2-mediated immunosuppression and recovering cytotoxic T-cell function. These findings establish OracleScreen-LILRB4 as an effective computational framework for accelerating small molecule discovery against non-enzymatic immune checkpoint targets.

25.
arXiv (CS.LG) 2026-06-15

Gradient boosting for extremes: sampling theory and application to insurance

arXiv:2606.14268v1 Announce Type: cross Abstract: We develop a statistical learning theory for gradient boosting applied to the estimation of covariate-dependent Generalized Pareto (GP) distributions in the context of Peaks-over-Threshold modeling. After an orthogonal reparametrization of the GP likelihood that diagonalizes its Fisher information matrix, we cast the estimation problem within the Empirical Risk Minimization (ERM) framework and derive non-asymptotic error bounds for the boosting estimator. Our analysis accounts for three distinct sources of error in the process: statistical fluctuations, the approximation bias inherent to the asymptotic nature of the GP model-controlled under second-order regular variation-and the approximation error associated with the finite number of boosting iterates, making explicit the resulting bias-variance trade-off. We illustrate the practical benefits of the reparametrization through simulations, showing that it significantly reduces gradient correlation during training and improves convergence stability. The methodology is applied to a medical malpractice insurance dataset from the Texas Department of Insurance, comprising over 18 000 closed claims. The gradient boosting approach yields a good fit for the tail of settlement cost distributions and reveals that the number of days to settlement is the dominant predictor of tail heaviness, consistent with earlier findings in the reserving literature.