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01.
arXiv (CS.AI) 2026-06-19

Simulation of Language Evolution under Regulated Social Media Platforms: A Synergistic Approach of Large Language Models and Genetic Algorithms

arXiv:2502.19193v2 Announce Type: replace-cross Abstract: Social media platforms frequently impose restrictive policies to moderate user content, prompting the emergence of creative evasion language strategies. This paper presents a multi-agent framework based on Large Language Models (LLMs) to simulate the iterative evolution of language strategies under regulatory constraints. In this framework, participant agents, as social media users, continuously evolve their language expression, while supervisory agents emulate platform-level regulation by assessing policy violations. To achieve a more faithful simulation, we employ a dual design of language strategies (constraint and expression) to differentiate conflicting goals and utilize an LLM-driven GA (Genetic Algorithm) for the selection, mutation, and crossover of language strategies. The framework is evaluated using two distinct scenarios: an abstract password game and a realistic simulated illegal pet trade scenario. Experimental results demonstrate that as the number of dialogue rounds increases, both the number of uninterrupted dialogue turns and the accuracy of information transmission improve significantly. Furthermore, a user study with 40 participants validates the real-world relevance of the generated dialogues and strategies. Moreover, ablation studies validate the importance of the GA, emphasizing its contribution to long-term adaptability and improved overall results.

02.
arXiv (quant-ph) 2026-06-12

Approximability limits for bounded-degree max-LINSAT and implications for decoded quantum interferometry

arXiv:2606.13570v1 Announce Type: new Abstract: For general max-k-XORSAT with $k \geq 3$, no polynomial-time algorithm can do substantially better than random guessing on worst-case instances unless $\mathsf{P} = \mathsf{NP}$: approximating beyond the random-assignment value of $1/2$ is $\mathsf{NP}$-hard. The picture changes when each variable appears in at most $D$ constraints. In that bounded-degree setting, polynomial-time algorithms can provably beat the random baseline by an additive amount of order $1/\sqrt{D}$. For Boolean instances, this scaling is known to be optimal: the matching hardness result is due to Trevisan, while the corresponding algorithmic guarantee was established by Barak et al. Whether the same holds over general finite fields, and what it implies for quantum algorithms, has not been established. We make this connection explicit and extend the hardness to max-E$k$-LINSAT$(q,r)$ with bounded degree $D$ and over arbitrary finite fields $\mathbb{F}_q$, proving that it is $\mathsf{NP}$-hard to exceed $r/q + \mathcal{O}_{q,r}(1/\sqrt{D})$. These results provide the complexity-theoretic benchmark for the bounded-degree instances targeted by decoded quantum interferometry (DQI), QAOA, and classical heuristics. Any quantum advantage on bounded-degree instances is therefore confined to the constant prefactor. We further show that in the context of DQI and on $(k,D)$-regular instances, this prefactor is sensitive to the nature of the decoder: DQI with classical decoders faces an information-theoretic $1/\sqrt{D \log D}$ barrier that prevents it from matching the hardness scaling, while DQI with quantum decoders is compatible with the $1/\sqrt{D}$ scaling – identifying quantum decoding as the key ingredient for matching the complexity-theoretic scaling with DQI.

03.
PLOS Computational Biology 2026-06-05

StPedf: Cell trajectory inference of spatial transcriptomics via spatial proximity embedding and spatial density-adaptive fusion

作者:

by Yuan Zhang, Ziyan Sun, Zhixin Shi, Mengdi Nan, Yuhan Fu, Qing Ren, Jie Gao Spatial transcriptomics is transforming our multidimensional understanding of cellular spatial organization and its functional mechanisms in processes such as development and disease by systematically resolving the spatial heterogeneity of gene expression within tissues. To delve deeper into the dynamic processes underlying spatial expression patterns, spatial trajectory inference integrates genetic and spatial information to reconstruct the spatial developmental trajectories of cells within tissues. This approach reveals the patterns of differentiation and dynamic changes as cellular states evolve continuously along spatial axes. However, existing methods often struggle to uniformly model the complex, nonlinear interactions between high-dimensional gene expression and spatial coordinates. Here, we introduce StPedf, whose core lies in employing a neural network with a masking mechanism to capture complex nonlinear interactions between high-dimensional genes and spatial positions. It further leverages spatial proximity information as a guiding cue, dynamically and adaptively adjusting the embedding of gene and spatial information and the weighting of spatial proximity information based on spatial density. This enables trajectory inference guided by spatial information. This enables optimal transport to derive intercellular transition matrices, reconstruct cellular differentiation trajectories, and construct pseudo-spatiotemporal maps. StPedf demonstrates superior performance over existing methods on five structurally distinct simulated datasets. Using StPedf, we successfully mapped distinct lineages in the spatial trajectories of telencephalon regeneration in the Ambystoma mexicanum, multiple malignant lineages expanding within primary tumors, and developmental spatial trajectories and pseudo-spatiotemporal maps in human dorsolateral prefrontal cortex (DLPFC). StPedf significantly enhances the accuracy and interpretability of spatial trajectory inference, providing critical technical support for revealing the dynamic patterns of cellular fate transitions within tissue microenvironments.

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

Towards Scalable Customization and Deployment of Multi-Agent Systems for Enterprise Applications

Large language model (LLM)-based multi-agent systems demonstrate strong performance on complex reasoning and task execution, enabling broad enterprise applications. However, production deployment remains challenging due to domain-specific customization requirements and high latency and inference costs in agentic workflows. We propose a unified framework for customization and efficient deployment of multi-agent systems in real-world settings. The first stage, Agentic Model Customization, combines continual pretraining, supervised fine-tuning, and preference optimization to adapt a compact model to specialized domains while retaining strong agentic capabilities. The second stage, Inference Optimization, integrates speculative decoding and FP8 quantization with targeted calibration to enable cost-efficient serving with minimal quality loss. Across enterprise workloads, our framework enables rapid domain adaptation and achieves a 4.48x speedup in throughput while maintaining performance and improving robustness on long-tail scenarios.

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

The Magic Barrier before Thermalization

arXiv:2510.11681v2 Announce Type: replace Abstract: We investigate the time dependence of anti-flatness in the entanglement spectrum, a measure for non-stabilizerness and lower bound for non-local quantum magic resource, on a subsystem of a linear SU(2) plaquette chain during thermalization. Tracing the time evolution of a large number of initial states, we find that the anti-flatness exhibits a barrier-like maximum during the time period when the entanglement entropy of the subsystem grows rapidly from the initial value to the microcanonical entropy. The location of the peak is strongly correlated with the time when the entanglement exhibits the strongest growth. This behavior is found for generic highly excited initial computational basis states and persists for coupling constants across the ergodic regime, revealing a universal structure of the entanglement spectrum during thermalization. We conclude that quantitative simulations of thermalization for nonabelian gauge theories require quantum computing. We speculate that this property generalizes to other quantum chaotic systems, a conjecture supported by analogous behavior observed in real-time simulations of the mixed-field Ising model.

07.
medRxiv (Medicine) 2026-06-11

Population-scale detection of methylation outliers from long-read genome sequencing

Background: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. Methods: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. Results: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. Conclusions: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

08.
arXiv (CS.LG) 2026-06-17

Operator Boosting Produces Pareto-Efficient PDE Surrogates

arXiv:2606.17460v1 Announce Type: new Abstract: Neural operators are widely used as surrogate solution maps for partial differential equations (PDEs), but full-size models can be costly to store, deploy, and evaluate in many-query scientific workflows. This work introduces Operator Boosting, a stagewise residual-learning framework for constructing compact neural-operator surrogates directly, rather than training a large model and compressing it afterward. Starting from the empirical mean predictor in normalized output coordinates, the method trains a sequence of tiny same-family neural operators on residual fields and incorporates each correction through validation-selected shrinkage. We instantiate the framework with Fourier neural operators (FNOs), DeepONets, and convolutional neural operators (CNOs), and compare boosted tiny stacks against full-size monolithic baselines across one-, two-, and three-dimensional PDE benchmarks from PDEBench, APEBench, and The Well. Across 30 dataset-architecture pairs, 21 show positive mean accuracy gains and 17 have positive confidence intervals, while all boosted stacks reduce trainable parameter count by approximately 72-95%. Best-model comparisons show empirical Pareto improvements on 7 of 10 completed PDE benchmarks, including two-dimensional Navier-Stokes, shallow-water dynamics, Darcy flow, one-dimensional transport and reaction systems, and three-dimensional compressible Navier-Stokes. These results show that Operator Boosting often improves the empirical accuracy-parameter Pareto frontier of neural PDE surrogates, while also exposing PDE- and architecture-dependent regimes where residual boosting fails to offset compression.

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

Weaving Multi-Source Evidence for Biomedical Reasoning: The BioMedHop Benchmark and BioWeave Framework

Biomedical question answering (QA) increasingly requires reasoning over interacting entities, where supporting evidence is scattered across biomedical knowledge graphs, literature documents, and web-accessible resources. However, existing biomedical QA benchmarks mainly focus on exam-style knowledge, literature comprehension, or short-range multi-hop inference, leaving source-conditioned graph reasoning and evidence topology construction underexplored. To fill this gap, we introduce BioMedHop, a multi-source graph-grounded benchmark for evaluating biomedical reasoning over structured evidence topologies. BioMedHop contains 10,045 instances across KG, document, web, and hybrid evidence settings, covering shared-neighbor matching, intersection reasoning, path-based reasoning, and counting, with option-based, open-ended, and numeric count renderings. To support this benchmark, we further propose BioWeave, a source-aware reasoning framework that retrieves biomedical KG paths, gathers supporting clues from documents and web sources, assembles them into a unified evidence graph, and verifies answers through entity-level evidence support. Comprehensive experiments show that BioWeave achieves the best overall performance among compared methods on BioMedHop, outperforming the strong hybrid baseline ToG-2 by 10.5% in the overall average. Moreover, BioWeave consistently improves different LLM backbones and enables smaller models, such as Qwen3-4B, to achieve reasoning performance comparable to GPT-4-Turbo.

10.
arXiv (CS.CL) 2026-06-16

A Large-Scale Multi-Dimensional Empirical Study of LLMs for Conversation Summarization

Despite the significant advancement of LLMs in conversation summarization, their evaluation remains limited by insufficient scenarios, input lengths, and sample sizes. Furthermore, existing benchmarks often omit frontier reasoning systems and efficient small models, or lack fine-grained, multi-dimensional assessments. To bridge these gaps, we propose OmniCSEval, a unified benchmark comprising 1,800 diverse conversations across six real-world scenarios, featuring context lengths ranging from 128 to 32k tokens. For fine-grained evaluation, we employ a bidirectional fact-checking framework that integrates key fact matching to assess completeness and conciseness, alongside summary fact verification to evaluate faithfulness. To ensure reliable assessment, we establish a human-LLM collaborative pipeline for key fact extraction and a multi-LLM consensus verifier for summary fact decomposition. Leveraging this framework, we evaluate 28 LLMs across four distinct categories grouped by reasoning capability and model scale. Our extensive empirical study reveals critical insights regarding the cross-scenario challenges current LLMs continue to face, the impacts of reasoning and scale, and the efficiency and adaptability of reasoning models. We also provide guidance for system selection in real-world deployments.

11.
arXiv (CS.AI) 2026-06-19

Creativity Reconsidered: Generative AI and the Problem of Intentional Agency

arXiv:2601.15797v2 Announce Type: replace Abstract: Many theorists maintain that conscious intentional agency is a necessary condition of creativity. We argue that this requirement, which we call the Intentional Agency Condition (IAC), should be abandoned. We motivate this by highlighting the problems this criterion encounters in the face of recent advances in generative AI, which is ostensibly creative despite being incapable of intentional agency. We present two corpus analyses to illustrate the rapidly increasing tendency of people to predicate creativity to generative AI. In response to this predicament, theorists of creativity have proposed a range of conflicting solutions, which we critically evaluate. We find that none of these satisfyingly resolves the initial predicament, and we therefore propose a novel approach. Our claim is that ascriptions of creativity are dependent on what we call creative ability. This solution explains why intentional agency is important for judgements of creativity, without being a necessary condition. Our approach thereby accommodates AI creativity without dismissing the intuition that perceived intentions are of key importance for ascriptions of creativity.

12.
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.

13.
arXiv (quant-ph) 2026-06-12

QuBE/Qubex: an integrated hardware-software system for superconducting qubit experiments with broadband control

arXiv:2606.13010v1 Announce Type: new Abstract: Achieving high-fidelity operation in large-scale superconducting qubit systems requires not only control hardware with broad frequency coverage, low crosstalk, and tight synchronization but also software that coordinates system configuration, experiment execution, and data analysis. Here we present an integrated qubit-control system that combines broadband microwave hardware with a pulse-level software stack for scalable superconducting qubit experiments. The hardware provides broadband microwave coverage, including an instantaneous span of up to 1.6 GHz from a control output, while the software reduces setup and calibration overhead through automated configuration and built-in experiment workflows. We validate the system on a 64-qubit fixed-frequency transmon chip through full-chip frequency identification and representative demonstrations, including multi-unit far-detuned cross-resonance calibration and benchmarking that yields a measured two-qubit gate fidelity of 98.34%, and multilevel readout beyond the computational subspace. By disclosing the hardware architecture and releasing the software stack as open source, this work provides an inspectable hardware-software foundation for scalable superconducting qubit control experiments.

14.
arXiv (quant-ph) 2026-06-16

Hardy and Cabello Arguments in Spatial and Temporal Frauchiger-Renner Scenarios

arXiv:2606.15467v1 Announce Type: new Abstract: We investigate Hardy- and Cabello-type logical structures within spatial and temporal extensions of the Frauchiger–Renner (FR) framework, embedding these constructions directly into the FR multi-observer architecture. In the spatial multi-observer scenario, both Hardy and Cabello contradictions arise, with the Cabello construction yielding the stronger violation,$\(\Delta_Cabello^{\max}=0.1078\)$, which exceeds the maximal Hardy probability $\(P_{H}^{\max}=\frac{5\sqrt{5}-11}{2}\approx 0.09017\)$. We then develop a sequential temporal FR protocol based on coherent multi-observer measurements performed on a single spin-$\tfrac12$ system. In this temporal setting, the Hardy contradiction disappears identically due to dynamical constraints imposed by sequential state updates, whereas a finite Cabello-type violation survives, \(\Delta_Cabello^{\max}\approx 0.0674\). Our results establish a fundamental structural distinction between spatial entanglement and temporal multi-observer correlations in FR-type logical scenarios, and demonstrate that certain observer-independent description failures persist even without spacelike separation.

15.
arXiv (quant-ph) 2026-06-19

Majorana bound states in a hybrid Kitaev ladder with long-range pairing

arXiv:2606.19963v1 Announce Type: new Abstract: We investigate an inter-leg coupled hybrid Kitaev ladder composed of two parallel superconducting chains with distinct pairing interactions. The upper chain of the ladder hosts conventional $p$-wave pairing, while the lower chain exhibits long-range pairing that decays algebraically with distance. We demonstrate that the mutual influence of long-range pairing exponent, chemical potential, and inter-leg coupling strength gives rise to a rich topological phase diagram characterized by multiple Majorana zero modes and massive Dirac modes. In particular, we show that the inter-leg coupling renormalizes the effective energy scales, leading to a systematic shift of the topological phase boundaries and enabling controlled tuning of the Majorana modes. Furthermore, we identify a transition from a two Majorana zero mode phase to a phase encapsulating four Majorana zero modes, as the long-range pairing exponent is varied. This transition is accompanied by a crossover regime in which Majorana zero modes coexist with massive Dirac modes, reflecting hybridization between edge and bulk excitations. This ladder thus provides a minimal and attractive platform for realizing the impact of a long-range pairing on topological phases. Our results highlight the potential of long-range hybrid systems for engineering tunable topological states relevant for quantum information applications.

16.
arXiv (CS.AI) 2026-06-12

Fault Lines: Navigating Ethics and Responsible AI Where National Policy Meets Local Practice in Public Sector Transformation

arXiv:2606.13039v1 Announce Type: cross Abstract: The UK government has adopted a pro-AI stance to help transform public service delivery in the face of severe financial pressures, but the path to translate this vision into responsible AI practice remains ill-defined. While UK policy is often set at the national level, local authorities are responsible for most public service delivery, and the rapid advance of AI-first narratives in the public sector is exposing fault lines in knowledge and practice at this national-local interface. This paper examines how responsible AI is interpreted and implemented at the interface between the UK's central government and local authorities, taking the high-stakes area of Special Educational Needs and Disabilities (SEND) as a case study. We present a thematic analysis of 17 semi-structured interviews with policymakers, practitioners, and third-sector professionals to identify barriers and enabling conditions for responsible AI where national policy meets local practice. We identify five interconnected challenges facing local authorities: shadow usage of AI and data privacy risks, market-government asymmetry in AI provision, insufficient workforce readiness, a lack of standardised definitions and measurements, and gaps in human accountability. For each, participants proposed actionable steps, from strengthening data protection frameworks and rebalancing the market-government relationship to enhancing workforce capacity. Our examination of SEND brings these challenges into sharper focus, showing how high-stakes decisions affecting vulnerable children and families intensify tensions around accountability, fairness, and human oversight, exposing the limits of a principle-based regulatory approach. We argue that responsible public sector AI requires both national policy adjustments and structural reforms to institutional capacity, values, and governance mechanisms at the local level.

17.
arXiv (CS.LG) 2026-06-16

Circuit Tracing in Autoregressive Protein Language Models

arXiv:2606.16044v1 Announce Type: new Abstract: Protein language models (pLMs) can generate novel protein sequences with properties beyond those observed in nature, yet the mechanisms underlying protein generation remain poorly understood. Existing mechanistic interpretability methods based on sparse autoencoders and transcoders primarily focus on protein representation learning models and do not capture the computation required for autoregressive generation. Here, we introduce ProGenMech, a mechanistic interpretability framework for generative protein language models that extends cross-layer transcoders (CLTs) to ProGen3, a sparse Mixture-of-Experts model trained for both causal generation and span infilling. Unlike per-layer approaches, CLTs reconstruct each layer using sparse latent variables from all preceding layers, enabling faithful recovery of inter-layer generative computation. We further develop a zero-shot circuit discovery framework to identify sparse latent circuits responsible for protein generation and fitness prediction. In causal generation and zero-shot fitness estimation tasks, ProGenMech outperforms local transcoder baselines in recovering ProGen3's probability distribution and functional scoring behavior, while matching the original model's generative distribution in span infilling tasks. Moreover, the recovered circuits reveal biologically meaningful motifs and functional regions associated with conserved sequence patterns and protein fitness landscapes, establishing a foundation for interpretable and steerable protein generation.

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

Information Leakage Detection through Approximate Bayes-optimal Prediction

arXiv:2401.14283v4 Announce Type: replace-cross Abstract: In today's data-driven world, the proliferation of publicly available information raises security concerns due to the information leakage (IL) problem. IL involves unintentionally exposing sensitive information to unauthorized parties via observable system information. Conventional statistical approaches rely on estimating mutual information (MI) between observable and secret information for detecting ILs, face challenges of the curse of dimensionality, convergence, computational complexity, and MI misestimation. Though effective, emerging supervised machine learning based approaches to detect ILs are limited to binary system sensitive information and lack a comprehensive framework. To address these limitations, we establish a theoretical framework using statistical learning theory and information theory to quantify and detect IL accurately. Using automated machine learning, we demonstrate that MI can be accurately estimated by approximating the typically unknown Bayes predictor's log-loss and accuracy. Based on this, we show how MI can effectively be estimated to detect ILs. Our method performs superior to state-of-the-art baselines in an empirical study considering synthetic and real-world OpenSSL TLS server datasets.

19.
arXiv (quant-ph) 2026-06-15

All about quantum error correction: distillation, mitigation, self-correction and beyond

作者:

arXiv:2606.14034v1 Announce Type: new Abstract: In this work, it is shown that many quantum error-manipulating techniques, such as distillation, error mitigation, and dynamical decoupling, are special cases of the most general framework for quantum error correction. This unifying perspective is achieved by extending quantum error correction to include state-adaptive and channel-adaptive settings, as well as multi-stage coding scenarios. Based on this insight, a model of self-correcting quantum memory is also proposed. This work clarifies the relationship among these techniques and illustrates, through explicit constructions, how the unified perspective can guide the design of reliable quantum information systems.

20.
medRxiv (Medicine) 2026-06-17

Deep learning for interactive and automated inner retinal layer segmentation in OCT images of patients with retinitis pigmentosa using limited training data

Purpose: New therapeutic strategies such as optogenetics have created a need for accurate tracking of inner retina degeneration in Retinitis pigmentosa (RP) patients. We introduce two tailored deep learning models to segment the RNFL (retinal nerve fibre layer), GCIPL (ganglion cell inner plexiform layer), INL (inner nuclear layer), CFT (central foveal thickness) and RPE (retinal pigment epithelium) in RP: The first is based on a Segment Anything Model (SAM), the second on nnU-Net. To our knowledge, SAM has not yet been applied to retinal layers in OCT data. Methods: SD-OCT images of a retrospective cohort of 37 RP patients were included. Data for four training cycles were prepared semi-automatically in MATLAB, then assessed and corrected by three expert graders. 1,700 segmented B-Scans from two open datasets were used for pretraining. For post-processing, semantic retinal boundary detection was developed. The final models, OCT-SAM and nnU-Net, were trained on 228 annotated RP scans. Detected layer thicknesses were validated against manual segmentation at 90 random points in 30 OCT B-Scans. Finally, OCT-SAM was tested on three RP cases with retrospective, longitudinal OCT data. Results: nnU-Net achieved a precision, recall and F-1 score of 0.96 while OCT-SAM performance resulted in slightly lower values of 0.93, 0.8 and 0.85, respectively. OCT-SAM measurements had low bias and good agreement with manual annotations, confirming reliability. Conclusions: OCT-SAM enabled fast data annotation and tool integration, whereas nnU-Net provided the best segmentation performance. OCT-SAM demonstrated longitudinal reproducibility and detected RP-characteristic pathologies and degenerative changes. Future work will extend OCT-SAM to 3D OCT segmentation.

21.
bioRxiv (Bioinfo) 2026-06-11

GermRL: Alleviating The Germline Bias In Autoregressive Antibody Language Models Through Reinforcement Learning

Antibodies are powerful therapeutics whose antigen specificity arises from sequence diversity shaped during development. Recently, language models trained on large antibody repertoire datasets have enabled the generation and screening of novel candidates, but these models retain a strong germline bias. As AI adoption increases in therapeutic workflows, it is crucial to develop models that harness the diversity of antibodies necessary for the discovery of mutations that encode desirable properties. Previous work explored the germline bias in masked antibody language models, yet the bias in generative autoregressive language models has not yet been addressed. Here, we present GermRL, a lightweight and modular reinforcement learning (RL) framework capable of alleviating the germline bias in pre-trained antibody autoregressive language models through group relative policy optimization (GRPO). GermRL achieves consistent one-shot generation of antibodies that satisfy specified mutation thresholds from germline while maintaining structural plausibility. Under the lowest and highest mutation thresholds tested (5 and 35 mutations from germline), GermRL scores 0.992 and 0.950 pass@1, respectively, compared to 0.398 and 0.034 for the pre-trained language model. Within GermRL, we introduce a key pair of modifications to GRPO that increase training efficiency by discouraging reward hacking under our antibody application. Furthermore, comparison of RL generated and natural antibody sequences reveals how RL based optimization can explore alternative evolutionary mutational patterns and residue compositional strategies while preserving key global properties of natural antibodies, including identifiable germline assignments, embedding-level similarity and comparable developability profiles. Thus, RL-trained generative models optimized to promote antibody mutations through diversity from germline provide a promising framework for navigating the antibody sequence landscape, enabling exploration of novel yet biologically plausible candidates for therapeutic design.

23.
medRxiv (Medicine) 2026-06-17

Multi-strain Probiotics Alter Gut Microbiota and Estrobolome Pathways in Primary Dysmenorrhea

Background: Exact cause of primary dysmenorrhoea is unknown but recent evidence uncovers a potential link between gut dysbiosis and benign gynaecological disorder via disruption of estrobolome. Methods: A randomized controlled trial to investigate the effects of multi-strain oral probiotics on primary dysmenorrhoea has been conducted. This is a secondary analysis comparing the stool microbiome in women with primary dysmenorrhoea and those without (control), and the effects of treatment with probiotics versus placebo. Results: Although microbial richness and evenness were comparable between groups (alpha diversity, p > 0.05), gut microbial community composition differed significantly (Bray Curtis PERMANOVA, p = 0.015), characterised by reduced Bifidobacterium adolescentis and Blautia and enrichment of Faecalibacterium in dysmenorrhoea, alongside condition-specific core taxa. Post-intervention analysis revealed significant shifts in microbial community structure between pre- and post-treatment groups (PERMANOVA, F = 2.11, p = 0.005), with probiotic supplementation inducing more consistent and directed microbiome changes than placebo, without altering alpha diversity (p > 0.05). Functional prediction showed no significant difference in overall beta glucuronidase pathway abundance (p > 0.05); however, dysmenorrhoea was associated with higher abundance of beta glucuronidase producing taxa (MaAsLin2, q < 0.05) that were differentially modulated by probiotic treatment. Conclusion: This discovery provides evidence on the microbial disruption in primary dysmenorrhoea as well as the benefit of probiotics to modulate the intestinal microbiota to improve the condition.

24.
medRxiv (Medicine) 2026-06-16

Cross-sectional study of the association between depressive symptoms and attentional bias to emotional stimuli in patients with acute stroke: Study protocol

Post-stroke depression affects approximately 30% of patients after stroke and is associated with delayed recovery in activities of daily living, reduced rehabilitation effectiveness, and poorer quality of life. Attentional bias modification may provide a low-burden, nonpharmacological approach for patients in the acute phase of stroke. However, before such an intervention can be implemented in clinical practice, it is necessary to clarify whether attentional bias is present in patients with acute stroke and depressive symptoms, whether cognitive function influences the manifestation of this bias, and which task and stimulus formats are most appropriate for assessment. This multicenter, cross-sectional observational study will enroll patients with acute stroke between 7-30 days after stroke onset. Depressive symptoms will be assessed using the depression subscale of the Hospital Anxiety and Depression Scale. Attentional bias will be measured under four task conditions based on the dot-probe task and the cue-target task, using face and word stimuli. Secondary assessments will include cognitive function, anxiety symptoms, activities of daily living, health-related quality of life, and clinical background variables. The aims of this study are to investigate the association between depressive symptoms and attentional bias in patients with acute stroke, compare attentional bias characteristics across task and stimulus types, and examine the potential influence of cognitive function on this association. The findings are expected to provide an empirical basis for designing future attentional bias modification protocols targeting post-stroke depression in the acute phase. This study has been registered with the UMIN Clinical Trials Registry (UMIN000059166).

25.
arXiv (CS.CV) 2026-06-17

m2sv: A Scalable Benchmark for Map-to-Street-View Spatial Reasoning

Vision–language models (VLMs) achieve strong performance on many multimodal benchmarks but remain brittle on spatial reasoning tasks that require aligning abstract overhead representations with egocentric views. We introduce m2sv, a scalable benchmark for map-to-street-view spatial reasoning that asks models to infer camera viewing direction by aligning a north-up overhead map with a Street View image captured at the same real-world intersection. We release m2sv-20k, a geographically diverse benchmark with controlled ambiguity, along with m2sv-sft-11k, a curated set of structured reasoning traces for supervised fine-tuning. Despite strong performance on existing multimodal benchmarks, the best evaluated VLM achieves only 65.2% accuracy on m2sv, below human annotators who reach 72.0% on average (and 95% for an expert) with strong inter-annotator agreement ($\kappa$ up to 0.76). While supervised fine-tuning and reinforcement learning yield consistent gains, cross-benchmark evaluations reveal limited transfer. Beyond aggregate accuracy, we systematically analyze difficulty in map-to-street-view reasoning using both structural signals and human effort, and conduct an extensive failure analysis of adapted open models. Our findings highlight persistent gaps in geometric alignment, evidence aggregation, and reasoning consistency, motivating future work on grounded spatial reasoning across viewpoints.