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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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Benchmarking AI Models in Software Engineering: A Review, Search Tool, and Unified Approach for Elevating Benchmark Quality

arXiv:2503.05860v3 Announce Type: replace-cross Abstract: Benchmarks are essential for unified evaluation and reproducibility. The rapid rise of Artificial Intelligence for Software Engineering (AI4SE) has produced numerous benchmarks for tasks such as code generation and bug repair. However, this proliferation has led to major challenges: (1) fragmented knowledge across tasks, (2) difficulty in selecting contextually relevant benchmarks, (3) lack of standardization in benchmark creation, and (4) flaws that limit utility. Addressing these requires a dual approach: systematically mapping existing benchmarks for informed selection and defining unified guidelines for robust, adaptable benchmark development. We conduct a review of 247 studies, identifying 273 AI4SE benchmarks since 2014. We categorize them, analyze limitations, and expose gaps in current practices. Building on these insights, we introduce BenchScout, an extensible semantic search tool for locating suitable benchmarks. BenchScout employs automated clustering with contextual embeddings of benchmark-related studies, followed by dimensionality reduction. In a user study with 22 participants, BenchScout achieved usability, effectiveness, and intuitiveness scores of 4.5, 4.0, and 4.1 out of 5. To improve benchmarking standards, we propose BenchFrame, a unified framework for enhancing benchmark quality. Applying BenchFrame to HumanEval yielded HumanEvalNext, featuring corrected errors, improved language conversion, higher test coverage, and greater difficulty. Evaluating 10 state-of-the-art code models on HumanEval, HumanEvalPlus, and HumanEvalNext revealed average pass-at-1 drops of 31.22% and 19.94%, respectively, underscoring the need for continuous benchmark refinement. We further examine BenchFrame's scalability through an agentic pipeline and confirm its generalizability on the MBPP dataset. All review data, user study materials, and enhanced benchmarks are publicly released.
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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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Mind the Gap! Pathways Towards Unifying AI Safety and Ethics Research

arXiv:2512.10058v1 Announce Type: new Abstract: While much research in artificial intelligence (AI) has focused on scaling capabilities, the accelerating pace of development makes countervailing work on producing harmless, "aligned" systems increasingly urgent. Yet research on alignment has diverged along two largely parallel tracks: safety--centered on scaled intelligence, deceptive or scheming behaviors, and existential risk--and ethics--focused on present harms, the reproduction of social bias, and flaws in production pipelines. Although both communities warn of insufficient investment in alignment, they disagree on what alignment means or ought to mean. As a result, their efforts have evolved in relative isolation, shaped by distinct methodologies, institutional homes, and disciplinary genealogies. We present a large-scale, quantitative study showing the structural split between AI safety and AI ethics. Using a bibliometric and co-authorship network analysis of 6,442 papers from twelve major ML and NLP conferences (2020-2025), we find that over 80% of collaborations occur within either the safety or ethics communities, and cross-field connectivity is highly concentrated: roughly 5% of papers account for more than 85% of bridging links. Removing a small number of these brokers sharply increases segregation, indicating that cross-disciplinary exchange depends on a handful of actors rather than broad, distributed collaboration. These results show that the safety-ethics divide is not only conceptual but institutional, with implications for research agendas, policy, and venues. We argue that integrating technical safety work with normative ethics--via shared benchmarks, cross-institutional venues, and mixed-method methodologies--is essential for building AI systems that are both robust and just.
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Are ultrasensitive ctDNA assays ready for clinical use in early-stage NSCLC?

Disease recurrence in early-stage non-small cell lung cancer (NSCLC) remains a persistent clinical challenge, underscoring the need for better prognostic biomarkers. In this preview, we highlight the clinical implications of ultrasensitive ctDNA monitoring in lung cancer risk modeling reported by Black et al. in this issue of Cell.
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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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Pancreatic Cancer Organoids: Modeling Disease and Guiding Therapy

Cancers (Basel). 2025 Nov 30;17(23):3850. doi: 10.3390/cancers17233850.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. An unmet need exists for reliable biomarkers and in vitro models capable of predicting patient drug response to advance personalized medicine. Traditional models fail to represent the tumor's complexity and the role of the stromal environment in chemoresistance. Patient-derived organoids (PDOs) overcome these limitations, enabling multi-omics profiling and reliable drug testing for functional precision medicine. This review provides a comprehensive overview of PDAC PDO research, emphasizing the following major areas: (i) the genetic and phenotypic fidelity of PDOs, (ii) their predictive value for drug response and chemoresistance, (iii) the integration of the extracellular matrix and tumor microenvironment (TME) components, and (iv) emerging technologies. Studies confirm that PDOs faithfully represent the primary tumor's specific genetic features and retain intratumoral heterogeneity. PDO-based platforms have demonstrated a strong correlation between in vitro drug sensitivity and in vivo efficacy in xenograft models, validating their utility for identifying drug candidates, repurposing existing drugs, and determining effective combinations. Efforts are ongoing to integrate crucial TME components, like cancer-associated fibroblasts, using innovative co-culture platforms such as fused PDOs and InterOMaX, to better model desmoplasia and chemoresistance mechanisms. Furthermore, PDO technology is converging with microphysiological systems and artificial intelligence tools to facilitate high-throughput drug screening and dynamic, real-time monitoring of therapeutic effects. The integration of PDOs into biobanks and advanced screening platforms holds the potential to accelerate drug discovery and improve therapeutic outcomes for PDAC patients, if challenges related to protocol standardization and regulatory acceptance are addressed.

PMID:41375051 | PMC:PMC12690986 | DOI:10.3390/cancers17233850

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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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Principles2Plan: LLM-Guided System for Operationalising Ethical Principles into Plans

arXiv:2512.08536v1 Announce Type: new Abstract: Ethical awareness is critical for robots operating in human environments, yet existing automated planning tools provide little support. Manually specifying ethical rules is labour-intensive and highly context-specific. We present Principles2Plan, an interactive research prototype demonstrating how a human and a Large Language Model (LLM) can collaborate to produce context-sensitive ethical rules and guide automated planning. A domain expert provides the planning domain, problem details, and relevant high-level principles such as beneficence and privacy. The system generates operationalisable ethical rules consistent with these principles, which the user can review, prioritise, and supply to a planner to produce ethically-informed plans. To our knowledge, no prior system supports users in generating principle-grounded rules for classical planning contexts. Principles2Plan showcases the potential of human-LLM collaboration for making ethical automated planning more practical and feasible.
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