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Does Less Hallucination Mean Less Creativity? An Empirical Investigation in LLMs

arXiv:2512.11509v1 Announce Type: cross Abstract: Large Language Models (LLMs) exhibit remarkable capabilities in natural language understanding and reasoning, but suffer from hallucination: the generation of factually incorrect content. While numerous methods have been developed to reduce hallucinations, their impact on creative generations remains unexplored. This gap is particularly critical for AI-assisted scientific discovery, which requires both factual accuracy and creative hypothesis generation. We investigate how three hallucination-reduction techniques: Chain of Verification (CoVe), Decoding by Contrasting Layers (DoLa), and Retrieval-Augmented Generation (RAG), affect creativity in LLMs. Evaluating multiple model families (LLaMA, Qwen, Mistral) at varying scales (1B - 70B parameters) on two creativity benchmarks (NeoCoder and CS4), we find that these methods have opposing effects on divergent creativity. CoVe enhances divergent thinking, DoLa suppresses it, and RAG shows minimal impact. Our findings provide guidance for selecting appropriate hallucination-reduction methods in scientific applications, where the balance between factual accuracy and creative exploration is crucial.
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From Verification Burden to Trusted Collaboration: Design Goals for LLM-Assisted Literature Reviews

arXiv:2512.11661v1 Announce Type: cross Abstract: Large Language Models (LLMs) are increasingly embedded in academic writing practices. Although numerous studies have explored how researchers employ these tools for scientific writing, their concrete implementation, limitations, and design challenges within the literature review process remain underexplored. In this paper, we report a user study with researchers across multiple disciplines to characterize current practices, benefits, and \textit{pain points} in using LLMs to investigate related work. We identified three recurring gaps: (i) lack of trust in outputs, (ii) persistent verification burden, and (iii) requiring multiple tools. This motivates our proposal of six design goals and a high-level framework that operationalizes them through improved related papers visualization, verification at every step, and human-feedback alignment with generation-guided explanations. Overall, by grounding our work in the practical, day-to-day needs of researchers, we designed a framework that addresses these limitations and models real-world LLM-assisted writing, advancing trust through verifiable actions and fostering practical collaboration between researchers and AI systems.
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Understanding Prompt Management in GitHub Repositories: A Call for Best Practices

arXiv:2509.12421v2 Announce Type: replace-cross Abstract: The rapid adoption of foundation models (e.g., large language models) has given rise to promptware, i.e., software built using natural language prompts. Effective management of prompts, such as organization and quality assurance, is essential yet challenging. In this study, we perform an empirical analysis of 24,800 open-source prompts from 92 GitHub repositories to investigate prompt management practices and quality attributes. Our findings reveal critical challenges such as considerable inconsistencies in prompt formatting, substantial internal and external prompt duplication, and frequent readability and spelling issues. Based on these findings, we provide actionable recommendations for developers to enhance the usability and maintainability of open-source prompts within the rapidly evolving promptware ecosystem.
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MetaVoxel: Joint Diffusion Modeling of Imaging and Clinical Metadata

arXiv:2512.10041v2 Announce Type: replace-cross Abstract: Modern deep learning methods have achieved impressive results across tasks from disease classification, estimating continuous biomarkers, to generating realistic medical images. Most of these approaches are trained to model conditional distributions defined by a specific predictive direction with a specific set of input variables. We introduce MetaVoxel, a generative joint diffusion modeling framework that models the joint distribution over imaging data and clinical metadata by learning a single diffusion process spanning all variables. By capturing the joint distribution, MetaVoxel unifies tasks that traditionally require separate conditional models and supports flexible zero-shot inference using arbitrary subsets of inputs without task-specific retraining. Using more than 10,000 T1-weighted MRI scans paired with clinical metadata from nine datasets, we show that a single MetaVoxel model can perform image generation, age estimation, and sex prediction, achieving performance comparable to established task-specific baselines. Additional experiments highlight its capabilities for flexible inference. Together, these findings demonstrate that joint multimodal diffusion offers a promising direction for unifying medical AI models and enabling broader clinical applicability.
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High-Throughput Dissection of Inter-Organ Genetic Networks: A Multi-Omic Systems Biology Approach

SLAS Technol. 2025 Dec 11:100376. doi: 10.1016/j.slast.2025.100376. Online ahead of print.

ABSTRACT

The existing multi-omic analyses are frequently confined to individual tissues, and the regulatory picture of the systemic regulator of complex physiology and disease is hidden. To fill this gap, we have created a unified systems biology model of the high-throughput dissection of inter-organ genetic networks. Our model incorporates transcriptomic, epigenomic and proteomic analysis of five major organs (liver, kidney, heart, lung, brain) using the Multi-Omics Factor Analysis (MOFA+) tool, specifically, cross-tissue coordination. We characterized 27 evidence-heavy cross-tissue modules (FDR < 0.05) that are major hubs such as *HNF4Aenda NRF2cheng8loadmasterregulatingconstitutionembryonicstemcellularinfoncogenes recognize them. One notable observation was liver-kidney metabolic axis, significant cross-talks in hepatocyte organoids are confirmed with CRISPR knockdown, which suppresses the expression of transporters expressed by the kidney. Our work offers a scalable validated framework that goes beyond organ-centric perspectives, which can be used as a potent tool of systemic disease modelling and precision medicine.

PMID:41389879 | DOI:10.1016/j.slast.2025.100376

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Stakeholder Criteria for Trust in Artificial Intelligence–Based Computer Perception Tools in Health Care: Qualitative Interview Study

Background: Computer perception (CP) technologies hold significant promise for advancing precision mental health care systems, given their ability to leverage algorithmic analysis of continuous, passive sensing data from wearables and smartphones (eg, behavioral activity, geolocation, vocal features, and ambient environmental data) to infer clinically meaningful behavioral and physiological states. However, successful implementation critically depends on cultivating well-founded stakeholder trust. Objective: This study aims to investigate, across adolescents, caregivers, clinicians, and developers, the contingencies under which CP technologies are deemed trustworthy in health care. Methods: We conducted 80 semistructured interviews with a purposive sample of adolescents (n=20) diagnosed with autism, Tourette syndrome, anxiety, obsessive-compulsive disorder, or attention-deficit/hyperactivity disorder and their caregivers (n=20); practicing clinicians across psychiatry, psychology, and pediatrics (n=20); and CP system developers (n=20). Interview transcripts were coded by 2 independent coders and analyzed using multistage, inductive thematic content analysis to identify prominent themes. Results: Across stakeholder groups, 5 core criteria emerged as prerequisites for trust in CP outputs: (1) epistemic alignment—consistency between system outputs, personal experience, and existing diagnostic frameworks; (2) demonstrable rigor—training on representative data and validation in real-world contexts; (3) explainability—transparent communication of input variables, thresholds, and decision logic; (4) sensitivity to complexity—the capacity to accommodate heterogeneity and comorbidity in symptom expression; and (5) a nonsubstitutive role—technologies must augment, rather than supplant, clinical judgment. A novel and cautionary finding was that epistemic alignment—whether outputs affirmed participants’ preexisting beliefs, diagnostic expectations, or internal states—was a dominant factor in determining whether the tool was perceived as trustworthy. Participants also expressed relational trust, placing confidence in CP systems based on endorsements from respected peers, academic institutions, or regulatory agencies. However, both trust strategies raise significant concerns: confirmation bias may lead users to overvalue outputs that align with their assumptions, while surrogate trust may be misapplied in the absence of robust performance validation. Conclusions: This study advances empirical understanding of how trust is formed and calibrated around artificial intelligence–based CP technologies. While trust is commonly framed as a function of technical performance, our findings show that it is deeply shaped by cognitive heuristics, social relationships, and alignment with entrenched epistemologies. These dynamics can facilitate intuitive verification but may also constrain the transformative potential of CP systems by reinforcing existing beliefs. To address this, we recommend a dual strategy: (1) embedding CP tools within institutional frameworks that uphold rigorous validation, ethical oversight, and transparent design; and (2) providing clinicians with training and interface designs that support critical appraisal and minimize susceptibility to cognitive bias. Recalibrating trust to reflect actual system capacities—rather than familiarity or endorsement—is essential for ethically sound and clinically meaningful integration of CP technologies.
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Exploring Health Misinformation Detection with Multi-Agent Debate

arXiv:2512.09935v1 Announce Type: new Abstract: Fact-checking health-related claims has become increasingly critical as misinformation proliferates online. Effective verification requires both the retrieval of high-quality evidence and rigorous reasoning processes. In this paper, we propose a two-stage framework for health misinformation detection: Agreement Score Prediction followed by Multi-Agent Debate. In the first stage, we employ large language models (LLMs) to independently evaluate retrieved articles and compute an aggregated agreement score that reflects the overall evidence stance. When this score indicates insufficient consensus-falling below a predefined threshold-the system proceeds to a second stage. Multiple agents engage in structured debate to synthesize conflicting evidence and generate well-reasoned verdicts with explicit justifications. Experimental results demonstrate that our two-stage approach achieves superior performance compared to baseline methods, highlighting the value of combining automated scoring with collaborative reasoning for complex verification tasks.
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Macrophage-targeted immunocytokine leverages myeloid, T, and NK cell synergy for cancer immunotherapy

MiTEs are myeloid-targeted immunocytokine prodrugs that block TREM2+ tumor-associated macrophages while activating cytotoxic lymphocytes via TME-specific IL-2 activity, eliciting strong anti-tumor efficacy in preclinical models with minimal systemic toxicity.
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Integrative network pharmacology, transcriptomics, and microbiomics elucidate the therapeutic mechanism of <em>Polygala tenuifolia</em> Willd water extract in chronic obstructive pulmonary disease

Front Microbiol. 2025 Nov 25;16:1703853. doi: 10.3389/fmicb.2025.1703853. eCollection 2025.

ABSTRACT

BACKGROUND: Polygala tenuifolia Willd (PT) is a plant with both medicinal and edible values. Traditionally, it has been used for sedation, enhancing cognition, resolving phlegm, and relieving cough. However, its protective effects and mechanisms against chronic obstructive pulmonary disease (COPD) remain unclear.

AIM OF THE STUDY: This study aims to observe the protective effects of the water extract of Polygala tenuifolia Willd (WEPT) on COPD, and to preliminarily elucidate its potential therapeutic mechanisms by integrating network pharmacology, molecular docking, multi-omics analysis, and molecular experiments.

METHODS AND MATERIALS: HPLC quantified WEPT constituents. COPD mice models established via chronic smoke exposure underwent WEPT treatment, and the therapeutic effect was evaluated by lung function test, histopathology and cytokine profiling. Integrated multi-omics analyses (network pharmacology, transcriptomics, microbiomics) identified bioactive compounds, therapeutic targets, pathway regulations, and microbiota dynamics. Molecular docking validated compound-target interactions, while immunohistochemical/fluorescence assays confirmed key protein expression in lung tissues.

RESULTS: WEPT administration effectively reduced inflammatory cytokine levels in COPD mice, improved lung function, and alleviated histopathological damage like alveolar structural injury and airway inflammation. Network pharmacology and transcriptomic analyses identified Norhyoscyamine and Onjixanthone I as key active components, targeting PIK3CA and AKT1 via PI3K-AKT pathway regulation. Microbiome analysis showed WEPT restored gut microbiota balance. Molecular docking confirmed strong binding of bioactive compounds to core targets, while immunostaining assays demonstrated WEPT suppressed p-PI3K and p-AKT protein expression.

CONCLUSION: WEPT may exert its intervention effects on COPD through a multi-target and multi-level comprehensive regulatory mechanism.

PMID:41377050 | PMC:PMC12685879 | DOI:10.3389/fmicb.2025.1703853

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AI-driven virtual cell models in preclinical research: technical pathways, validation mechanisms, and clinical translation potential

npj Digital Medicine, Published online: 11 December 2025; doi:10.1038/s41746-025-02198-6

AI-driven virtual cell models in preclinical research: technical pathways, validation mechanisms, and clinical translation potential
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Toward an AI Reasoning-Enabled System for Patient-Clinical Trial Matching

arXiv:2512.08026v1 Announce Type: new Abstract: Screening patients for clinical trial eligibility remains a manual, time-consuming, and resource-intensive process. We present a secure, scalable proof-of-concept system for Artificial Intelligence (AI)-augmented patient-trial matching that addresses key implementation challenges: integrating heterogeneous electronic health record (EHR) data, facilitating expert review, and maintaining rigorous security standards. Leveraging open-source, reasoning-enabled large language models (LLMs), the system moves beyond binary classification to generate structured eligibility assessments with interpretable reasoning chains that support human-in-the-loop review. This decision support tool represents eligibility as a dynamic state rather than a fixed determination, identifying matches when available and offering actionable recommendations that could render a patient eligible in the future. The system aims to reduce coordinator burden, intelligently broaden the set of trials considered for each patient and guarantee comprehensive auditability of all AI-generated outputs.
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Beyond Traditional Diagnostics: Transforming Patient-Side Information into Predictive Insights with Knowledge Graphs and Prototypes

arXiv:2512.08261v1 Announce Type: new Abstract: Predicting diseases solely from patient-side information, such as demographics and self-reported symptoms, has attracted significant research attention due to its potential to enhance patient awareness, facilitate early healthcare engagement, and improve healthcare system efficiency. However, existing approaches encounter critical challenges, including imbalanced disease distributions and a lack of interpretability, resulting in biased or unreliable predictions. To address these issues, we propose the Knowledge graph-enhanced, Prototype-aware, and Interpretable (KPI) framework. KPI systematically integrates structured and trusted medical knowledge into a unified disease knowledge graph, constructs clinically meaningful disease prototypes, and employs contrastive learning to enhance predictive accuracy, which is particularly important for long-tailed diseases. Additionally, KPI utilizes large language models (LLMs) to generate patient-specific, medically relevant explanations, thereby improving interpretability and reliability. Extensive experiments on real-world datasets demonstrate that KPI outperforms state-of-the-art methods in predictive accuracy and provides clinically valid explanations that closely align with patient narratives, highlighting its practical value for patient-centered healthcare delivery.
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Multi-Agent Intelligence for Multidisciplinary Decision-Making in Gastrointestinal Oncology

arXiv:2512.08674v1 Announce Type: new Abstract: Multimodal clinical reasoning in the field of gastrointestinal (GI) oncology necessitates the integrated interpretation of endoscopic imagery, radiological data, and biochemical markers. Despite the evident potential exhibited by Multimodal Large Language Models (MLLMs), they frequently encounter challenges such as context dilution and hallucination when confronted with intricate, heterogeneous medical histories. In order to address these limitations, a hierarchical Multi-Agent Framework is proposed, which emulates the collaborative workflow of a human Multidisciplinary Team (MDT). The system attained a composite expert evaluation score of 4.60/5.00, thereby demonstrating a substantial improvement over the monolithic baseline. It is noteworthy that the agent-based architecture yielded the most substantial enhancements in reasoning logic and medical accuracy. The findings indicate that mimetic, agent-based collaboration provides a scalable, interpretable, and clinically robust paradigm for automated decision support in oncology.
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Towards Foundation Models with Native Multi-Agent Intelligence

arXiv:2512.08743v1 Announce Type: new Abstract: Foundation models (FMs) are increasingly assuming the role of the "brain" of AI agents. While recent efforts have begun to equip FMs with native single-agent abilities -- such as GUI interaction or integrated tool use -- we argue that the next frontier is endowing FMs with native multi-agent intelligence. We identify four core capabilities of FMs in multi-agent contexts: understanding, planning, efficient communication, and adaptation. Contrary to assumptions about the spontaneous emergence of such abilities, we provide extensive empirical evidence across 41 large language models showing that strong single-agent performance alone does not automatically yield robust multi-agent intelligence. To address this gap, we outline key research directions -- spanning dataset construction, evaluation, training paradigms, and safety considerations -- for building FMs with native multi-agent intelligence.
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Biothreat Benchmark Generation Framework for Evaluating Frontier AI Models I: The Task-Query Architecture

arXiv:2512.08130v1 Announce Type: cross Abstract: Both model developers and policymakers seek to quantify and mitigate the risk of rapidly-evolving frontier artificial intelligence (AI) models, especially large language models (LLMs), to facilitate bioterrorism or access to biological weapons. An important element of such efforts is the development of model benchmarks that can assess the biosecurity risk posed by a particular model. This paper describes the first component of a novel Biothreat Benchmark Generation (BBG) Framework. The BBG approach is designed to help model developers and evaluators reliably measure and assess the biosecurity risk uplift and general harm potential of existing and future AI models, while accounting for key aspects of the threat itself that are often overlooked in other benchmarking efforts, including different actor capability levels, and operational (in addition to purely technical) risk factors. As a pilot, the BBG is first being developed to address bacterial biological threats only. The BBG is built upon a hierarchical structure of biothreat categories, elements and tasks, which then serves as the basis for the development of task-aligned queries. This paper outlines the development of this biothreat task-query architecture, which we have named the Bacterial Biothreat Schema, while future papers will describe follow-on efforts to turn queries into model prompts, as well as how the resulting benchmarks can be implemented for model evaluation. Overall, the BBG Framework, including the Bacterial Biothreat Schema, seeks to offer a robust, re-usable structure for evaluating bacterial biological risks arising from LLMs across multiple levels of aggregation, which captures the full scope of technical and operational requirements for biological adversaries, and which accounts for a wide spectrum of biological adversary capabilities.
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ClinicalTrialsHub: Bridging Registries and Literature for Comprehensive Clinical Trial Access

arXiv:2512.08193v1 Announce Type: cross Abstract: We present ClinicalTrialsHub, an interactive search-focused platform that consolidates all data from ClinicalTrials.gov and augments it by automatically extracting and structuring trial-relevant information from PubMed research articles. Our system effectively increases access to structured clinical trial data by 83.8% compared to relying on ClinicalTrials.gov alone, with potential to make access easier for patients, clinicians, researchers, and policymakers, advancing evidence-based medicine. ClinicalTrialsHub uses large language models such as GPT-5.1 and Gemini-3-Pro to enhance accessibility. The platform automatically parses full-text research articles to extract structured trial information, translates user queries into structured database searches, and provides an attributed question-answering system that generates evidence-grounded answers linked to specific source sentences. We demonstrate its utility through a user study involving clinicians, clinical researchers, and PhD students of pharmaceutical sciences and nursing, and a systematic automatic evaluation of its information extraction and question answering capabilities.
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Biothreat Benchmark Generation Framework for Evaluating Frontier AI Models III: Implementing the Bacterial Biothreat Benchmark (B3) Dataset

arXiv:2512.08459v1 Announce Type: cross Abstract: The potential for rapidly-evolving frontier artificial intelligence (AI) models, especially large language models (LLMs), to facilitate bioterrorism or access to biological weapons has generated significant policy, academic, and public concern. Both model developers and policymakers seek to quantify and mitigate any risk, with an important element of such efforts being the development of model benchmarks that can assess the biosecurity risk posed by a particular model. This paper discusses the pilot implementation of the Bacterial Biothreat Benchmark (B3) dataset. It is the third in a series of three papers describing an overall Biothreat Benchmark Generation (BBG) framework, with previous papers detailing the development of the B3 dataset. The pilot involved running the benchmarks through a sample frontier AI model, followed by human evaluation of model responses, and an applied risk analysis of the results along several dimensions. Overall, the pilot demonstrated that the B3 dataset offers a viable, nuanced method for rapidly assessing the biosecurity risk posed by a LLM, identifying the key sources of that risk and providing guidance for priority areas of mitigation priority.
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AI-powered virtual tissues from spatial proteomics for clinical diagnostics and biomedical discovery

arXiv:2501.06039v2 Announce Type: replace-cross Abstract: Spatial proteomics technologies have transformed our understanding of complex tissue architecture in cancer but present unique challenges for computational analysis. Each study uses a different marker panel and protocol, and most methods are tailored to single cohorts, which limits knowledge transfer and robust biomarker discovery. Here we present Virtual Tissues (VirTues), a general-purpose foundation model for spatial proteomics that learns marker-aware, multi-scale representations of proteins, cells, niches and tissues directly from multiplex imaging data. From a single pretrained backbone, VirTues supports marker reconstruction, cell typing and niche annotation, spatial biomarker discovery, and patient stratification, including zero-shot annotation across heterogeneous panels and datasets. In triple-negative breast cancer, VirTues-derived biomarkers predict anti-PD-L1 chemo-immunotherapy response and stratify disease-free survival in an independent cohort, outperforming state-of-the-art biomarkers derived from the same datasets and current clinical stratification schemes.
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OMNIGUARD: An Efficient Approach for AI Safety Moderation Across Languages and Modalities

arXiv:2505.23856v2 Announce Type: replace-cross Abstract: The emerging capabilities of large language models (LLMs) have sparked concerns about their immediate potential for harmful misuse. The core approach to mitigate these concerns is the detection of harmful queries to the model. Current detection approaches are fallible, and are particularly susceptible to attacks that exploit mismatched generalization of model capabilities (e.g., prompts in low-resource languages or prompts provided in non-text modalities such as image and audio). To tackle this challenge, we propose Omniguard, an approach for detecting harmful prompts across languages and modalities. Our approach (i) identifies internal representations of an LLM/MLLM that are aligned across languages or modalities and then (ii) uses them to build a language-agnostic or modality-agnostic classifier for detecting harmful prompts. Omniguard improves harmful prompt classification accuracy by 11.57\% over the strongest baseline in a multilingual setting, by 20.44\% for image-based prompts, and sets a new SOTA for audio-based prompts. By repurposing embeddings computed during generation, Omniguard is also very efficient ($\approx\!120 \times$ faster than the next fastest baseline). Code and data are available at: https://github.com/vsahil/OmniGuard.
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