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Efficient and safe transduction of cochlear outer hair cells in adult mice with AAV2.7m8-Myo15

This study identifies AAV2.7m8-Myo15 as a safe and efficient vector for transducing cochlear outer hair cells in adult mice via posterior semicircular canal injection. These insights overcome age-related transduction barriers and suggest potential gene therapy strategies for sensorineural hearing loss.
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MultiPhishGuard: An Explainable and Adaptive Multi-Agent LLM System for Phishing Email Detection

arXiv:2505.23803v2 Announce Type: replace-cross Abstract: Phishing email detection faces significant challenges due to evolving adversarial tactics and heterogeneous attack patterns. Traditional approaches, such as rule-based filters and denylists, often struggle to keep pace, leading to missed detections and security risks. While machine learning methods have improved detection performance, they remain limited in adapting to novel and rapidly changing phishing strategies. We present MultiPhishGuard, an LLM-based multi-agent detection framework with learned coordination across specialized agents. The system consists of five cooperative agents (text, URL, metadata, explanation simplifier, and adversarial agents), with agent contributions dynamically weighted using Proximal Policy Optimization. To address emerging threats, the framework incorporates an adversarial training loop in which an LLM-based agent generates subtle, context-aware email variants to expose potential model weaknesses and improve robustness to ambiguous phishing cases. Experimental evaluations on public datasets show that MultiPhishGuard achieves stronger performance than established baselines, including Chain-of-Thought prompting and single-agent variants, as supported by ablation studies and comparative analyses. The system achieves an accuracy of 97.89%, with a false positive rate of 2.73% and a false negative rate of 0.20%. In addition, an explanation simplifier agent transforms technical model outputs into plain-language rationales intended for human users. Overall, these results suggest that multi-agent LLM architectures with adaptive coordination and adversarial training represent a promising direction for phishing email detection.
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Characterization and regulatory mechanism evaluation of C8orf33 in hepatocellular carcinoma through multiomics profiling

Discov Oncol. 2026 Apr 11. doi: 10.1007/s12672-026-04951-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Chromosome 8 open reading frame 33 (C8orf33) has been noted as a potential oncogenic factor in several cancers, but its biological roles and regulatory mechanism in HCC microenvironment remain unknown.

METHODS: We integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) to characterize the expression landscape of C8orf33. We then performed C8orf33 loss-of-function studies in HCC cell lines, including in vitro phenotypic assays and subcutaneous xenografts.

RESULTS: C8orf33 was broadly overexpressed and associated with unfavorable prognosis across multiple Cancers. In HCC, higher C8orf33 aligned with advanced stage and shorter overall survival. C8orf33 knockdown reduced proliferation and migration, impaired tumorigenic capacity, and increased apoptosis. ScRNA-seq analyses identified a malignant population of Epi3 with high C8orf33 expression. Cell-cell communication analysis suggested that C8orf33-high Epi3 state was associated with an enriched MIF-CD74/CXCR4/CD44 signaling program toward macrophage populations with M2-like features. ST analyses further confirmed the colocalization of C8orf33 with malignant features in tumor cores. In Huh7 cells, C8orf33 knockdown was accompanied by reduced mRNA and protein levels of MIF and its receptor components. Consistently, xenografts derived from C8orf33-silenced cells showed lower expression of these MIF-axis components and reduced infiltration of CD163 and CD206-positive macrophages.

CONCLUSION: These results support a tumor-promoting association of C8orf33 in HCC and suggest a potential link to macrophage-associated immunomodulatory features, nominating C8orf33 as a candidate biomarker and therapeutic target.

PMID:41965457 | DOI:10.1007/s12672-026-04951-z

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Characterization and regulatory mechanism evaluation of C8orf33 in hepatocellular carcinoma through multiomics profiling

Discov Oncol. 2026 Apr 11. doi: 10.1007/s12672-026-04951-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Chromosome 8 open reading frame 33 (C8orf33) has been noted as a potential oncogenic factor in several cancers, but its biological roles and regulatory mechanism in HCC microenvironment remain unknown.

METHODS: We integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) to characterize the expression landscape of C8orf33. We then performed C8orf33 loss-of-function studies in HCC cell lines, including in vitro phenotypic assays and subcutaneous xenografts.

RESULTS: C8orf33 was broadly overexpressed and associated with unfavorable prognosis across multiple Cancers. In HCC, higher C8orf33 aligned with advanced stage and shorter overall survival. C8orf33 knockdown reduced proliferation and migration, impaired tumorigenic capacity, and increased apoptosis. ScRNA-seq analyses identified a malignant population of Epi3 with high C8orf33 expression. Cell-cell communication analysis suggested that C8orf33-high Epi3 state was associated with an enriched MIF-CD74/CXCR4/CD44 signaling program toward macrophage populations with M2-like features. ST analyses further confirmed the colocalization of C8orf33 with malignant features in tumor cores. In Huh7 cells, C8orf33 knockdown was accompanied by reduced mRNA and protein levels of MIF and its receptor components. Consistently, xenografts derived from C8orf33-silenced cells showed lower expression of these MIF-axis components and reduced infiltration of CD163 and CD206-positive macrophages.

CONCLUSION: These results support a tumor-promoting association of C8orf33 in HCC and suggest a potential link to macrophage-associated immunomodulatory features, nominating C8orf33 as a candidate biomarker and therapeutic target.

PMID:41965457 | DOI:10.1007/s12672-026-04951-z

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Low-Burden LLM-Based Preference Learning: Personalizing Assistive Robots from Natural Language Feedback for Users with Paralysis

arXiv:2604.01463v1 Announce Type: cross Abstract: Physically Assistive Robots (PARs) require personalized behaviors to ensure user safety and comfort. However, traditional preference learning methods, like exhaustive pairwise comparisons, cause severe physical and cognitive fatigue for users with profound motor impairments. To solve this, we propose a low-burden, offline framework that translates unstructured natural language feedback directly into deterministic robotic control policies. To safely bridge the gap between ambiguous human speech and robotic code, our pipeline uses Large Language Models (LLMs) grounded in the Occupational Therapy Practice Framework (OTPF). This clinical reasoning decodes subjective user reactions into explicit physical and psychological needs, which are then mapped into transparent decision trees. Before deployment, an automated "LLM-as-a-Judge" verifies the code's structural safety. We validated this system in a simulated meal preparation study with 10 adults with paralysis. Results show our natural language approach significantly reduces user workload compared to traditional baselines. Additionally, independent clinical experts confirmed the generated policies are safe and accurately reflect user preferences.
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Ran Score: a LLM-based Evaluation Score for Radiology Report Generation

arXiv:2603.22935v1 Announce Type: new Abstract: Chest X-ray report generation and automated evaluation are limited by poor recognition of low-prevalence abnormalities and inadequate handling of clinically important language, including negation and ambiguity. We develop a clinician-guided framework combining human expertise and large language models for multi-label finding extraction from free-text chest X-ray reports and use it to define Ran Score, a finding-level metric for report evaluation. Using three non-overlapping MIMIC-CXR-EN cohorts from a public chest X-ray dataset and an independent ChestX-CN validation cohort, we optimize prompts, establish radiologist-derived reference labels and evaluate report generation models. The optimized framework improves the macro-averaged score from 0.753 to 0.956 on the MIMIC-CXR-EN development cohort, exceeds the CheXbert benchmark by 15.7 percentage points on directly comparable labels, and shows robust generalization on the ChestX-CN validation cohort. Here we show that clinician-guided prompt optimization improves agreement with a radiologist-derived reference standard and that Ran Score enables finding-level evaluation of report fidelity, particularly for low-prevalence abnormalities.
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Biomolecular profiling for noninvasive health monitoring

Nature Biotechnology, Published online: 12 March 2026; doi:10.1038/s41587-026-03050-2

Kim et al. present mass spectrometry and wearable sensor technology as complementary approaches that, when integrated, can co-evolve to open new possibilities for noninvasive health monitoring.
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CMI-RewardBench: Evaluating Music Reward Models with Compositional Multimodal Instruction

arXiv:2603.00610v2 Announce Type: replace-cross Abstract: While music generation models have evolved to handle complex multimodal inputs mixing text, lyrics, and reference audio, evaluation mechanisms have lagged behind. In this paper, we bridge this critical gap by establishing a comprehensive ecosystem for music reward modeling under Compositional Multimodal Instruction (CMI), where the generated music may be conditioned on text descriptions, lyrics, and audio prompts. We first introduce CMI-Pref-Pseudo, a large-scale preference dataset comprising 110k pseudo-labeled samples, and CMI-Pref, a high-quality, human-annotated corpus tailored for fine-grained alignment tasks. To unify the evaluation landscape, we propose CMI-RewardBench, a unified benchmark that evaluates music reward models on heterogeneous samples across musicality, text-music alignment, and compositional instruction alignment. Leveraging these resources, we develop CMI reward models (CMI-RMs), a parameter-efficient reward model family capable of processing heterogeneous inputs. We evaluate their correlation with human judgments scores on musicality and alignment on CMI-Pref along with previous datasets. Further experiments demonstrate that CMI-RM not only correlates strongly with human judgments, but also enables effective inference-time scaling via top-k filtering. The necessary training data, benchmarks, and reward models are publicly available.
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Whom to Query for What: Adaptive Group Elicitation via Multi-Turn LLM Interactions

arXiv:2602.14279v1 Announce Type: cross Abstract: Eliciting information to reduce uncertainty about latent group-level properties from surveys and other collective assessments requires allocating limited questioning effort under real costs and missing data. Although large language models enable adaptive, multi-turn interactions in natural language, most existing elicitation methods optimize what to ask with a fixed respondent pool, and do not adapt respondent selection or leverage population structure when responses are partial or incomplete. To address this gap, we study adaptive group elicitation, a multi-round setting where an agent adaptively selects both questions and respondents under explicit query and participation budgets. We propose a theoretically grounded framework that combines (i) an LLM-based expected information gain objective for scoring candidate questions with (ii) heterogeneous graph neural network propagation that aggregates observed responses and participant attributes to impute missing responses and guide per-round respondent selection. This closed-loop procedure queries a small, informative subset of individuals while inferring population-level responses via structured similarity. Across three real-world opinion datasets, our method consistently improves population-level response prediction under constrained budgets, including a >12% relative gain on CES at a 10% respondent budget.
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