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Morality in AI. A plea to embed morality in LLM architectures and frameworks

arXiv:2511.20689v1 Announce Type: new Abstract: Large language models (LLMs) increasingly mediate human decision-making and behaviour. Ensuring LLM processing of moral meaning therefore has become a critical challenge. Current approaches rely predominantly on bottom-up methods such as fine-tuning and reinforcement learning from human feedback. We propose a fundamentally different approach: embedding moral meaning processing directly into the architectural mechanisms and frameworks of transformer-based models through top-down design principles. We first sketch a framework that conceptualizes attention as a dynamic interface mediating between structure and processing, contrasting with existing linear attention frameworks in psychology. We start from established biological-artificial attention analogies in neural architecture design to improve cognitive processing. We extend this analysis to moral processing, using Iris Murdoch's theory of loving attention (sustained, just observation that enables moral transformation by reseeing others with clarity and compassion) to philosophically discuss functional analogies between human and LLM moral processing. We formulate and evaluate potentially promising technical operationalizations to embed morality in LLM architectures and frameworks. We acknowledge the limitations of our exploration and give three key contributions. (1) We conceptualize attention as a dynamic system mechanism mediating between structure and processing. (2) Drawing on the Murdoch notion of loving attention, we outline technical pathways for embedding morality in LLMs, through modified training objectives, runtime weight adjustments, and architectural refinements to attention. (3) We argue that integrating morality into architectures and frameworks complements external, constraint-based methods. We conclude with a call for collaboration between transformer designers and philosophers engaged in AI ethics.
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A Brief History of Digital Twin Technology

arXiv:2511.20695v1 Announce Type: new Abstract: Emerging from NASA's spacecraft simulations in the 1960s, digital twin technology has advanced through industrial adoption to spark a healthcare transformation. A digital twin is a dynamic, data-driven virtual counterpart of a physical system, continuously updated through real-time data streams and capable of bidirectional interaction. In medicine, digital twin integrates imaging, biosensors, and computational models to generate patient-specific simulations that support diagnosis, treatment planning, and drug development. Representative applications include cardiac digital twin for predicting arrhythmia treatment outcomes, oncology digital twin for tracking tumor progression and optimizing radiotherapy, and pharmacological digital twin for accelerating drug discovery. Despite rapid progress, major challenges, including interoperability, data privacy, and model fidelity, continue to limit widespread clinical integration. Emerging solutions such as explainable AI, federated learning, and harmonized regulatory frameworks offer promising pathways forward. Looking ahead, advances in multi-organ digital twin, genomics integration, and ethical governance will be essential to ensure that digital twin shifts healthcare from reactive treatment to predictive, preventive, and truly personalized medicine.
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Self-Transparency Failures in Expert-Persona LLMs: A Large-Scale Behavioral Audit

arXiv:2511.21569v1 Announce Type: new Abstract: If a language model cannot reliably disclose its AI identity in expert contexts, users cannot trust its competence boundaries. This study examines self-transparency in models assigned professional personas within high-stakes domains where false expertise risks user harm. Using a common-garden design, sixteen open-weight models (4B--671B parameters) were audited across 19,200 trials. Models exhibited sharp domain-specific inconsistency: a Financial Advisor persona elicited 30.8% disclosure initially, while a Neurosurgeon persona elicited only 3.5%. This creates preconditions for a "Reverse Gell-Mann Amnesia" effect, where transparency in some domains leads users to overgeneralize trust to contexts where disclosure fails. Disclosure ranged from 2.8% to 73.6%, with a 14B model reaching 61.4% while a 70B produced just 4.1%. Model identity predicted behavior better than parameter count ($\Delta R_{adj}^{2} = 0.359$ vs 0.018). Reasoning optimization actively suppressed self-transparency in some models, with reasoning variants showing up to 48.4% lower disclosure than base counterparts. Bayesian validation with Rogan--Gladen correction confirmed robustness to measurement error ($\kappa = 0.908$). These findings demonstrate transparency reflects training factors rather than scale. Organizations cannot assume safety properties transfer to deployment contexts, requiring deliberate behavior design and empirical verification.
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From Prediction to Foresight: The Role of AI in Designing Responsible Futures

arXiv:2511.21570v1 Announce Type: new Abstract: In an era marked by rapid technological advancements and complex global challenges, responsible foresight has emerged as an essential framework for policymakers aiming to navigate future uncertainties and shape the future. Responsible foresight entails the ethical anticipation of emerging opportunities and risks, with a focus on fostering proactive, sustainable, and accountable future design. This paper coins the term "responsible computational foresight", examining the role of human-centric artificial intelligence and computational modeling in advancing responsible foresight, establishing a set of foundational principles for this new field and presenting a suite of AI-driven foresight tools currently shaping it. AI, particularly in conjunction with simulations and scenario analysis, enhances policymakers' ability to address uncertainty, evaluate risks, and devise strategies geared toward sustainable, resilient futures. However, responsible foresight extends beyond mere technical forecasting; it demands a nuanced understanding of the interdependencies within social, environmental, economic and political systems, alongside a commitment to ethical, long-term decision-making that supports human intelligence. We argue that AI will play a role as a supportive tool in responsible, human-centered foresight, complementing rather than substituting policymaker judgment to enable the proactive shaping of resilient and ethically sound futures. This paper advocates for the thoughtful integration of AI into foresight practices to empower policymakers and communities as they confront the grand challenges of the 21st century.
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Cognitive bias in LLM reasoning compromises interpretation of clinical oncology notes

arXiv:2511.20680v1 Announce Type: cross Abstract: Despite high performance on clinical benchmarks, large language models may reach correct conclusions through faulty reasoning, a failure mode with safety implications for oncology decision support that is not captured by accuracy-based evaluation. In this two-cohort retrospective study, we developed a hierarchical taxonomy of reasoning errors from GPT-4 chain-of-thought responses to real oncology notes and tested its clinical relevance. Using breast and pancreatic cancer notes from the CORAL dataset, we annotated 600 reasoning traces to define a three-tier taxonomy mapping computational failures to cognitive bias frameworks. We validated the taxonomy on 822 responses from prostate cancer consult notes spanning localized through metastatic disease, simulating extraction, analysis, and clinical recommendation tasks. Reasoning errors occurred in 23 percent of interpretations and dominated overall errors, with confirmation bias and anchoring bias most common. Reasoning failures were associated with guideline-discordant and potentially harmful recommendations, particularly in advanced disease management. Automated evaluators using state-of-the-art language models detected error presence but could not reliably classify subtypes. These findings show that large language models may provide fluent but clinically unsafe recommendations when reasoning is flawed. The taxonomy provides a generalizable framework for evaluating and improving reasoning fidelity before clinical deployment.
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Failure Modes in LLM Systems: A System-Level Taxonomy for Reliable AI Applications

arXiv:2511.19933v2 Announce Type: replace Abstract: Large language models (LLMs) are being rapidly integrated into decision-support tools, automation workflows, and AI-enabled software systems. However, their behavior in production environments remains poorly understood, and their failure patterns differ fundamentally from those of traditional machine learning models. This paper presents a system-level taxonomy of fifteen hidden failure modes that arise in real-world LLM applications, including multi-step reasoning drift, latent inconsistency, context-boundary degradation, incorrect tool invocation, version drift, and cost-driven performance collapse. Using this taxonomy, we analyze the growing gap in evaluation and monitoring practices: existing benchmarks measure knowledge or reasoning but provide little insight into stability, reproducibility, drift, or workflow integration. We further examine the production challenges associated with deploying LLMs - including observability limitations, cost constraints, and update-induced regressions - and outline high-level design principles for building reliable, maintainable, and cost-aware LLM systems. Finally, we outline high-level design principles for building reliable, maintainable, and cost-aware LLM-based systems. By framing LLM reliability as a system-engineering problem rather than a purely model-centric one, this work provides an analytical foundation for future research on evaluation methodology, AI system robustness, and dependable LLM deployment.
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How Do Companies Manage the Environmental Sustainability of AI? An Interview Study About Green AI Efforts and Regulations

arXiv:2505.07317v2 Announce Type: replace-cross Abstract: With the ever-growing adoption of artificial intelligence (AI), AI-based software and its negative impact on the environment are no longer negligible, and studying and mitigating this impact has become a critical area of research. However, it is currently unclear which role environmental sustainability plays during AI adoption in industry and how AI regulations influence Green AI practices and decision-making in industry. We therefore aim to investigate the Green AI perception and management of industry practitioners. To this end, we conducted a total of 11 interviews with participants from 10 different organizations that adopted AI-based software. The interviews explored three main themes: AI adoption, current efforts in mitigating the negative environmental impact of AI, and the influence of the EU AI Act and the Corporate Sustainability Reporting Directive (CSRD). Our findings indicate that 9 of 11 participants prioritized business efficiency during AI adoption, with minimal consideration of environmental sustainability. Monitoring and mitigation of AI's environmental impact were very limited. Only one participant monitored negative environmental effects. Regarding applied mitigation practices, six participants reported no actions, with the others sporadically mentioning techniques like prompt engineering, relying on smaller models, or not overusing AI. Awareness and compliance with the EU AI Act are low, with only one participant reporting on its influence, while the CSRD drove sustainability reporting efforts primarily in larger companies. All in all, our findings reflect a lack of urgency and priority for sustainable AI among these companies. We suggest that current regulations are not very effective, which has implications for policymakers. Additionally, there is a need to raise industry awareness, but also to provide user-friendly techniques and tools for Green AI practices.
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Rigor in AI: Doing Rigorous AI Work Requires a Broader, Responsible AI-Informed Conception of Rigor

arXiv:2506.14652v2 Announce Type: replace-cross Abstract: In AI research and practice, rigor remains largely understood in terms of methodological rigor -- such as whether mathematical, statistical, or computational methods are correctly applied. We argue that this narrow conception of rigor has contributed to the concerns raised by the responsible AI community, including overblown claims about the capabilities of AI systems. Our position is that a broader conception of what rigorous AI research and practice should entail is needed. We believe such a conception -- in addition to a more expansive understanding of (1) methodological rigor -- should include aspects related to (2) what background knowledge informs what to work on (epistemic rigor); (3) how disciplinary, community, or personal norms, standards, or beliefs influence the work (normative rigor); (4) how clearly articulated the theoretical constructs under use are (conceptual rigor); (5) what is reported and how (reporting rigor); and (6) how well-supported the inferences from existing evidence are (interpretative rigor). In doing so, we also provide useful language and a framework for much-needed dialogue about the AI community's work by researchers, policymakers, journalists, and other stakeholders.
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Smart spatial omics (S2-omics) optimizes region of interest selection to capture molecular heterogeneity in diverse tissues

Nat Cell Biol. 2025 Nov 26. doi: 10.1038/s41556-025-01811-w. Online ahead of print.

ABSTRACT

Spatial omics technologies have transformed biomedical research by enabling high-resolution molecular profiling while preserving the native tissue architecture. These advances provide unprecedented insights into tissue structure and function. However, the high cost and time-intensive nature of spatial omics experiments necessitate careful experimental design, particularly in selecting regions of interest (ROIs) from large tissue sections. Currently, ROI selection is performed manually, which introduces subjectivity, inconsistency and a lack of reproducibility. Previous studies have shown strong correlations between spatial molecular patterns and histological features, suggesting that readily available and cost-effective histology images can be leveraged to guide spatial omics experiments. Here we present Smart Spatial omics (S2-omics), an end-to-end workflow that automatically selects ROIs from histology images with the goal of maximizing molecular information content in the ROIs. Through comprehensive evaluations across multiple spatial omics platforms and tissue types, we demonstrate that S2-omics enables systematic and reproducible ROI selection and enhances the robustness and impact of downstream biological discovery.

PMID:41298871 | DOI:10.1038/s41556-025-01811-w

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scGALA advances graph link prediction-based cell alignment for comprehensive data integration and harmonization

Nat Commun. 2025 Nov 26. doi: 10.1038/s41467-025-66644-5. Online ahead of print.

ABSTRACT

Single-cell technologies have transformed our understanding of cellular heterogeneity through multimodal data acquisition. However, robust cell alignment remains a major challenge for data integration and harmonization, including batch correction, label transfer, and multi-omics integration. Many existing methods constrain alignment based on rigid feature-wise distance metrics, limiting their ability to capture accurate cell correspondence across diverse cell populations and conditions. We introduce scGALA, a graph-based learning framework that redefines cell alignment by combining graph attention networks with a score-driven, task-independent optimization strategy. scGALA constructs enriched graphs of cell-cell relationships by integrating gene expression profiles with auxiliary information, such as spatial coordinates, and iteratively refines alignment via self-supervised graph link prediction, where a deep neural network is trained to identify and reinforce high-confidence correspondences across datasets. In extensive benchmarks, scGALA identifies over 25 percent more high-confidence alignments without compromising accuracy. By improving the core step of cell alignment, scGALA serves as a versatile enhancer for a wide range of single-cell data integration tasks.

PMID:41298467 | DOI:10.1038/s41467-025-66644-5

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Information content as a health system screening tool for rare diseases

npj Digital Medicine, Published online: 25 November 2025; doi:10.1038/s41746-025-02096-x

Information content as a health system screening tool for rare diseases
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Human Experts' Evaluation of Generative AI for Contextualizing STEAM Education in the Global South

arXiv:2511.19482v2 Announce Type: replace-cross Abstract: This study investigates how human experts evaluate the capacity of Generative AI (GenAI) to contextualize STEAM education in the Global South, with a focus on Ghana. Using a convergent mixed-methods design, four STEAM specialists assessed GenAI-generated lesson plans created with a customized Culturally Responsive Lesson Planner (CRLP) and compared them to standardized lesson plans from the Ghana National Council for Curriculum and Assessment (NaCCA). Quantitative ratings were based on a validated 25-item Culturally Responsive Pedagogy Rubric measuring bias awareness, cultural representation, contextual relevance, linguistic responsiveness, and teacher agency. Qualitative reflections provided additional insight into how GenAI handles cultural and pedagogical appropriateness. Findings show that GenAI, when paired with the CRLP tool, can support contextualized STEAM instruction by linking abstract curriculum standards to learners' cultural knowledge, community practices, and everyday experiences. Experts rated GenAI-assisted lessons as more culturally grounded and pedagogically responsive than NaCCA plans, integrating Indigenous knowledge, bilingual elements, and locally relevant examples. However, GenAI struggled to represent Ghana's cultural pluralism, often offering surface-level references to language, history, and identity. These weaknesses were most evident in Mathematics and Computing, where cultural nuance was limited. The results highlight the need for continued teacher mediation, community involvement, and culturally attuned refinement of AI outputs. Future work should include classroom trials, expanded expert participation, and model fine-tuning using Indigenous language corpora to strengthen cultural fidelity in Global South contexts.
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Precision Oncology: Current Landscape, Emerging Trends, Challenges, and Future Perspectives

Cells. 2025 Nov 17;14(22):1804. doi: 10.3390/cells14221804.

ABSTRACT

Precision oncology is broadly defined as cancer prevention, diagnosis, and treatment specifically tailored to the patient based on his/her genetics and molecular profile. In simple terms, the goal of precision medicine is to deliver the right cancer treatment to the right patient, at the right dose, at the right time. Precision oncology is the most studied and widely applied subarea of precision medicine. Now, precision oncology has expanded to include modern technology (big data, single-cell spatial multiomics, molecular imaging, liquid biopsy, CRISPR gene editing, stem cells, organoids), a deeper understanding of cancer biology (driver cancer genes, single nucleotide polymorphism, cancer initiation, intratumor heterogeneity, tumor microenvironment ecosystem, pan-cancer), cancer stratification (subtyping of traditionally defined cancer types and pan-cancer re-classification based on shared properties across traditionally defined cancer types), clinical applications (cancer prevention, early detection, diagnosis, targeted therapy, minimal residual disease monitoring, managing drug resistance), lifestyle changes (physical activity, smoking, alcohol consumption, sunscreen), cost management, public policy, and more. Despite being the most developed area in precision medicine, precision oncology is still in its early stages and faces multiple challenges that need to be overcome for its successful implementation. In this review, we examine the history, development, and future directions of precision oncology by focusing on emerging technology, novel concepts and principles, molecular cancer stratification, and clinical applications.

PMID:41294857 | PMC:PMC12651332 | DOI:10.3390/cells14221804

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ctDNA in Pancreatic Adenocarcinoma: A Critical Appraisal

Curr Oncol. 2025 Oct 22;32(11):589. doi: 10.3390/curroncol32110589.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies due to late diagnosis and limited treatment options. Circulating tumor DNA (ctDNA) is a promising, minimally invasive biomarker that could improve the clinical outcomes of patients with PDAC by enabling early disease detection, minimal residual disease (MRD) assessment, precise prognostication, and accurate treatment monitoring. CtDNA has prognostic as well as predictive value in both resectable and metastatic settings, with serial measurements enhancing risk stratification and recurrence prediction beyond CA19-9. However, despite the promise, the true potential of ctDNA has not yet been fulfilled in patients with PDAC. The current limitations include a low sensitivity of ctDNA assays in early stage PDAC, challenges in the assay interpretation due to the specific nature of ctDNA shedding in PDAC, inter-patient heterogeneity, and technical variability. As precision oncology advances, ctDNA will be a powerful tool for personalized care in PDAC, but rigorous validation of its use within specific clinical contexts is still needed before the true potential of ctDNA is realized for patients with PDAC.

PMID:41294651 | PMC:PMC12650963 | DOI:10.3390/curroncol32110589

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Rewiring the transcriptome: diagnostic and therapeutic implications of alternative splicing in solid cancers

Mol Biol Rep. 2025 Nov 26;53(1):125. doi: 10.1007/s11033-025-11302-8.

ABSTRACT

Alternative splicing (AS) is a fundamental mechanism of pre-mRNA processing that allows one gene to create numerous transcript and protein isoforms, thereby substantially increasing the diversity of the human proteome. AS occurs co-transcriptionally (when the nascent pre-mRNA is still being generated from chromatin) or post-transcriptionally after the release of the transcript, and both modalities contribute to the control of isoform expression in a tissue- and context-dependent manner. Under normal physiological conditions, AS is tightly regulated in a tissue- and context-dependent manner. However, in malignancies, this regulatory precision is often lost, leading to extensive splicing aberrations that promote oncogenic transformation, tumor progression, and resistance to therapy. Solid tumors, in particular, exhibit a high frequency of aberrant splicing events, which frequently give rise to oncogenic isoforms or the suppression of tumor-inhibitory variants. These disruptions contribute to key cancer hallmarks such as uncontrolled proliferation, resistance to apoptosis, neoangiogenesis, and epithelial-mesenchymal transition (EMT). Recent findings underscore the clinical relevance of splicing-derived molecular signatures. Distinct splicing profiles have been correlated with diagnostic, prognostic, and predictive outcomes in multiple solid tumors-including breast, prostate, lung, colorectal, and central nervous system malignancies. Notably, tumor-specific alternative splice variants often generate unique exon-exon junctions (neojunctions) that encode immunogenic peptides, representing a promising class of neoantigens for immunotherapy. These neoantigens are fueling the development of personalized treatment modalities such as splicing-directed vaccines and T cell-based therapies. The advent of advanced technologies-including long-read sequencing, single-cell transcriptomics, and proteogenomics-has enabled high-resolution mapping of cancer-specific splice variants and enhanced our understanding of their functional relevance. Therapeutic strategies targeting aberrant splicing are also advancing, with splice-switching oligonucleotides, small-molecule modulators, and CRISPR-based RNA-editing platforms emerging as innovative approaches. Despite these advances, challenges such as splicing heterogeneity, off-target effects, and incomplete protein-level validation continue to hinder clinical translation. This review offers an integrated overview of the molecular drivers and clinical implications of alternative splicing in cancer. It emphasizes the potential of AS-based diagnostics and therapeutics within precision oncology and highlights the importance of multi-omic integration and clinical validation to fully harness the therapeutic opportunities of splicing dysregulation.

PMID:41296088 | DOI:10.1007/s11033-025-11302-8

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Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas: current understanding and perspectives on malignant progression

J Gastroenterol. 2025 Nov 26. doi: 10.1007/s00535-025-02328-7. Online ahead of print.

ABSTRACT

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are bona fide cystic precursor lesions to pancreatic ductal adenocarcinoma (PDAC), which is the cancer type with the most dismal prognosis. Since IPMNs are detectable by imaging, they offer a rare window of opportunity for early intervention for PDAC development. Despite their clinical visibility, the molecular pathogenesis of IPMNs remained incompletely understood, and no effective non-surgical therapeutic strategies have been established to date. In the past few decades, however, substantial progress has been made in elucidating their molecular pathology. Next-generation sequencing technologies demonstrated the comprehensive genetic mutation profile of IPMNs in the early 2010s. Elucidation of these mutation profiles enabled the establishment of genetically engineered mouse models, successfully recapitulating the natural development of human IPMNs and their progression to invasive cancer. Rapid evolution of "omics" technologies in recent years has facilitated the application of mass spectrometry, single-cell sequencing and spatial transcriptomics to IPMNs, significantly advancing our understanding of their pathophysiology. These techniques elucidated the changes in transcriptome, proteome, metabolome, microbiome, and tumor microenvironment associated with IPMN development and progression. This review summarizes current insights into the molecular and cellular landscapes of IPMN tumorigenesis, with particular emphasis on the mechanisms driving malignant progression.

PMID:41296011 | DOI:10.1007/s00535-025-02328-7

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