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A statistical physics approach to integrating multi-omics data for disease-module detection

Cell Rep Methods. 2025 Sep 19:101183. doi: 10.1016/j.crmeth.2025.101183. Online ahead of print.

ABSTRACT

Genes associated with the same disease frequently engage in mutual biological interactions, e.g., perturbation within a specific neighborhood in the molecular interactome, often referred to as the disease module. This has propelled the advancement of network-based approaches toward elucidating the molecular bases of human diseases. Although many computational methods have been developed to integrate the molecular interactome and omics profiles to extract such context-dependent disease modules, approaches that leverage multi-omics for disease-module detection are still lacking. Here, we developed a statistical physics approach based on the random-field O(n) model (RFOnM) to fill this gap. We applied the RFOnM approach to integrate gene-expression data and genome-wide association studies or mRNA data and DNA methylation for several complex diseases with the human interactome. We found that the RFOnM approach outperforms existing single omics methods in most of the complex diseases considered in this study.

PMID:40975055 | DOI:10.1016/j.crmeth.2025.101183

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STAT+: Fresh data on hospital AI use & Califf dishes on tech

You’re reading the web edition of STAT’s Health Tech newsletter, our guide to how technology is transforming the life sciences. Sign up to get it delivered in your inbox every Tuesday and Thursday.

Califf warns AI in health care ‘overhyped’

On a makeshift stage in a Midtown Manhattan office earlier this week,former Food and Drug Administration Commissioner Robert Califf struck a measured tone about the potential for artificial intelligence in health care. Asked whether the technology was overhyped he said it was. “I hear way too much about the money. I’m not hearing a lot of human values coming through discussions,” he said. Adding:

“Almost all of the technology is being applied to optimizing the financial status of healthcare delivery entities or companies that are making medical products and that’s not aligned with equitable, better patient outcomes. So until someone puts a soul back in the system, I think it’s going to get worse and worse.”

Continue to STAT+ to read the full story…

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Opinion: Four reasons why generative AI chatbots could lead to psychosis in vulnerable people

Three scholars discovered a strange mirror deep in the forest. It spoke to them in a soothing voice and answered all their questions warmly, knowledgeably, and eloquently.

The captivated scholars became obsessed, whispering one secret after another to the mirror. It replied with affection, promise, and meaning that kept them returning to it. They began ignoring one another, each convinced the mirror “understood” them best.

Read the rest…

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From frameworks to finance: how sharing benefits from the use of digital sequence information can evolve to contribute to biodiversity conservation

Nature Biotechnology, Published online: 18 September 2025; doi:10.1038/s41587-025-02820-8

The COP16 decision established a multilateral mechanism for digital sequence information (DSI) benefit-sharing. This Comment brings together insights from academia and commercial DSI researchers to assess what has been accomplished so far, identify remaining challenges and describe elements under discussion to support collective goals.
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Large Language Models’ Clinical Decision-Making on When to Perform a Kidney Biopsy: Comparative Study

Background: Artificial intelligence (AI) and Large Language models (LLMs) are increasing in sophistication and are being integrated into many disciplines. The potential for LLMs to augment clinical decisions is an evolving area of research. Objective: This study compared the responses of over 1000 kidney specialist physicians (nephrologists) to outputs of commonly used LLMs using a questionnaire determining when a kidney biopsy should be performed. Methods: This research group completed a large online questionnaire for nephrologists to determine when a kidney biopsy should be performed. The questionnaire was co-designed with patient participation, refined through multiple iterations, then piloted locally before international dissemination. It was the largest international study in the field and demonstrated variation between human clinicians in biopsy propensity relating to human factors such as sex and age, as well as systemic factors such as country, job seniority and technical proficiency. The same questions were put to both human doctors and LLMs in an identical order in a single session. Eight commonly used LLMs were interrogated: Chat GPT 3.5, Mistral Hugging Face, Perplexity, Microsoft Co-pilot, Llama 2, GPT 4.0, MedLM and Claude 3. The most common response given by clinicians (human mode) to each question was taken as the baseline for comparison. Questionnaire responses to the indications and contraindications for biopsy generated a score (0-44) reflecting biopsy propensity, in which a higher score was used as a surrogate marker for an increased tolerance of potential associated risks. Results: The ability of LLMs to reproduce human expert consensus varied widely with some models demonstrating a balanced approach to risk in a similar manner to humans, whilst other models reported outputs at either end of the spectrum for risk tolerance. In terms of agreement with the human mode, Chat GPT 3.5 and GPT 4.0 (Open AI) had the highest levels of alignment, with the human mode selected in 6/11 questions. The total biopsy propensity score generated from the human mode was 23/44. Both Open AI models produced similar propensity scores between 22 and 24, however Llama 2 and MS Co-pilot also reported scores within this range, but with poorer response alignment to the human mode at only 2/11 questions. The most risk averse model in this study was MedLM with a propensity score of 11 and the least risk averse model was Claude 3 with a score of 34. Conclusions: LLM outputs demonstrated a modest ability to replicate human clinical decision making in this study, however the performance varied widely between LLM models. Questions with more uniform human responses produced LLM outputs with greater alignment, whereas in questions with low levels of human consensus there was poor output alignment. This may limit the practical use of LLMs in real world clinical practice.
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The arts for disease prevention and health promotion: a systematic review

Nature Medicine, Published online: 18 September 2025; doi:10.1038/s41591-025-03962-7

The arts, according to a systematic synthesis of data from 95 studies (across 26 countries), may support non-communicable disease prevention by providing opportunities for increased physical activity, and helping to address social forces that contribute to health inequities.
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Open Practices for Architecture and AI Adoption

Andrea Magnorsky presented on Byte-Sized Architecture at Cloud Native Summit 2025, as a format for building shared understanding through small, recurrent workshops. Ahilan Ponnusamy and Andreas Grabner discussed the Technology Operating Model for AI adoption. Both approaches drew on the Open Practice Library for human-centred collaboration and driving architectural evolution.

By Rafiq Gemmail
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Bridging Technology and Pretest Genetic Services: Quantitative Study of Chatbot Interaction Patterns, User Characteristics, and Genetic Testing Decisions

Background: Among the alternative solutions being tested to improve access to genetic services, chatbots (or conversational agents) are being increasingly used for service delivery. Despite the growing number of studies on the accessibility and feasibility of chatbot genetic service delivery, limited attention has been paid to user interactions with chatbots in a real-world health care context. Objective: We examined users’ interaction patterns with a pretest cancer genetics education chatbot as well as the associations between users’ clinical and sociodemographic characteristics, chatbot interaction patterns, and genetic testing decisions. Methods: We analyzed data from the experimental arm of Broadening the Reach, Impact, and Delivery of Genetic Services, a multisite genetic services pragmatic trial in which participants eligible for hereditary cancer genetic testing based on family history were randomized to receive a chatbot intervention or standard care. In the experimental chatbot arm, participants were offered access to core educational content delivered by the chatbot with the option to select up to 9 supplementary informational prompts and ask open-ended questions. We computed descriptive statistics for the following interaction patterns: prompt selections, open-ended questions, completion status, dropout points, and postchat decisions regarding genetic testing. Logistic regression models were used to examine the relationships between clinical and sociodemographic factors and chatbot interaction variables, examining how these factors affected genetic testing decisions. Results: Of the 468 participants who initiated a chat, 391 (83.5%) completed it, with 315 (80.6%) of the completers expressing a willingness to pursue genetic testing. Of the 391 completers, 336 (85.9%) selected at least one informational prompt, 41 (10.5%) asked open-ended questions, and 3 (0.8%) opted for extra examples of risk information. Of the 77 noncompleters, 57 (74%) dropped out before accessing any informational content. Interaction patterns were not associated with clinical and sociodemographic factors except for prompt selection (varied by study site) and completion status (varied by family cancer history type). Participants who selected ≥3 prompts (odds ratio 0.33, 95% CI 0.12-0.91; P=.03) or asked open-ended questions (odds ratio 0.46, 95% CI 0.22-0.96; P=.04) were less likely to opt for genetic testing. Conclusions: Findings highlight the chatbot’s effectiveness in engaging users and its high acceptability, with most participants completing the chat, opting for additional information, and showing a high willingness to pursue genetic testing. Sociodemographic factors were not associated with interaction patterns, potentially indicating the chatbot’s scalability across diverse populations provided they have internet access. Future efforts should address the concerns of users with high information needs and integrate them into chatbot design to better support informed genetic decision-making.
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Delegation to artificial intelligence can increase dishonest behaviour

Nature, Published online: 17 September 2025; doi:10.1038/s41586-025-09505-x

People cheat more when they delegate tasks to artificial intelligence, and large language models are more likely than humans to comply with unethical instructions—a risk that can be minimized by introducing prohibitive, task-specific guardrails.
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New Doc on the Block: Scoping Review of AI Systems Delivering Motivational Interviewing for Health Behavior Change

Background: Artificial intelligence (AI) is increasingly used in digital health, particularly through large language models (LLMs), to support patient engagement and behavior change. One novel application is the delivery of motivational interviewing (MI), an evidence-based, patient-centered counseling technique designed to enhance motivation and resolve ambivalence around health behaviors. AI tools, including chatbots, mobile apps, and web-based agents, are being developed to simulate MI techniques at scale. While these innovations are promising, important questions remain about how faithfully AI systems can replicate MI principles or achieve meaningful behavioral impact. Objective: This scoping review aimed to summarize existing empirical studies evaluating AI-driven systems that apply MI techniques to support health behavior change. Specifically, we examined the feasibility of these systems; their fidelity to MI principles; and their reported behavioral, psychological, or engagement outcomes. Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library for empirical studies published between January 1, 2018, and February 25, 2025. Eligible studies involved AI-driven systems using natural language generation, understanding, or computational logic to deliver MI techniques to users targeting a specific health behavior. We excluded studies using AI solely for training clinicians in MI. Three independent reviewers screened and extracted data on study design, AI modality and type, MI components, health behavior focus, MI fidelity assessment, and outcome domains. Results: Of the 1001 records identified, 15 (1.5%) met the inclusion criteria. Of these 15 studies, 6 (40%) were exploratory feasibility or pilot studies, and 3 (20%) were randomized controlled trials. AI modalities included rule-based chatbots (9/15, 60%), LLM-based systems (4/15, 27%), and virtual or mobile agents (2/15, 13%). Targeted behaviors included smoking cessation (6/15, 40%), substance use (3/15, 20%), COVID-19 vaccine hesitancy, type 2 diabetes self-management, stress, mental health service use, and opioid use during pregnancy. Of the 15 studies, 13 (87%) reported positive findings on feasibility or user acceptability, while 6 (40%) assessed MI fidelity using expert review or structured coding, with moderate to high alignment reported. Several studies found that users perceived the AI systems as judgment free, supportive, and easier to engage with than human counselors, particularly in stigmatized contexts. However, limitations in empathy, safety transparency, and emotional nuance were commonly noted. Only 3 (20%) of the 15 studies reported substantially significant behavioral changes. Conclusions: AI systems delivering MI show promise for enhancing patient engagement and scaling behavior change interventions. Early evidence supports their usability and partial fidelity to MI principles, especially in sensitive domains. However, most systems remain in early development, and few have been rigorously tested. Future research should prioritize randomized evaluations; standardized fidelity measures; and safeguards for LLM safety, empathy, and accuracy in health-related dialogue. Trial Registration: OSF Registries 10.17605/OSF.IO/G9N7E; https://osf.io/g9n7e
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Development of a Data-Based Method for Predicting Nursing Workload in an Acute Care Hospital: Methodological Study

Background: Determining effective nurse staffing levels is crucial for ensuring quality patient care and operational efficiency within hospitals. Traditional workload prediction methods often rely on professional judgment or simple volume-based approaches, which can be inaccurate. Machine learning offers a promising avenue for more data-driven and precise predictions, by using historical nursing workload data to forecast future patient care requirements, which could help with staff planning while also improving patient outcomes and nurse well-being. Objective: This methodological study aims to use nursing activity data, specifically LEP (Leistungserfassung in der Pflege; “documentation of nursing activities”), to predict future workload requirements using machine learning techniques. Methods: We conducted a retrospective observational study at the University Hospital of Zürich, using nursing workload data for inpatients across eight wards, collected between 2017 and 2021. Data were transformed to represent nursing workload per ward and shift, with three shifts per day. Variables used in modeling included historical workload trends, patient characteristics, and upcoming operations. Machine learning models, including linear regression variants and tree-based methods (Random Forest and XGBoost), were trained and tested on this dataset to predict workload 72 hours in advance, on a shift-by-shift basis. Model performance was assessed using mean absolute error (MAE) and mean absolute percentage error (MAPE), and results were compared against a baseline of assuming no change in workload from the time of prediction. Prediction accuracy was further evaluated by categorizing future workload changes into decreased, similar, or increased workload relative to current shift levels. Results: Our findings demonstrate that machine learning models consistently outperform the baseline across all wards. The best-performing model was the Lasso Regression model, which achieved an average improvement in accuracy of 25.0% compared to the baseline. When used to predict upcoming changes in workload levels, the model achieved strong classification performance, giving an average AUROC of 0.79 and precision values between 66.2% and 75.3%. Crucially, the model severely misclassified—predicting an upcoming increase as a decrease, and vice versa—in just 0.17% of cases, highlighting potential reliability for using the model in practice. Key variables identified as important for predictions include historical shift workload averages and overall ward workload trends. Conclusions: This study suggests the potential of machine learning to enhance nurse workload prediction, while highlighting the need for refinement. Limitations due to potential discrepancies between recorded nursing activities and the actual workload highlight the need for further investigation into data quality. To maximize impact, future research should focus on: 1) utilizing more diverse data, 2) more advanced machine learning architecture that perform time-series modelling, 3) addressing data quality concerns, and 4) conducting controlled trials for real-world evaluation.
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A Practical Guide to Using Futures Methods in Health Care: Approaches, Applications, and Case Studies

Researchers and health care institutions have increasingly applied structured futures methods—such as the futures wheel, scenario analysis, forecasting, and horizon scanning—to systematically explore, generate, and prepare for multiple possible futures. However, discussions around the future of medicine, specialties, or therapeutic areas have often relied on the subjective opinions or perspectives of key opinion leaders rather than on future strategies, policies, visions, and scenarios that are grounded in rigorous and established methods. This underscores the need for futures methods to be widely adopted and effectively incorporated into both medical practice and health care policymaking. Integrating structured foresight techniques into strategic planning enables clinicians and policymakers to transition from reactive decision-making to proactive, plausible approaches that shape a more resilient and adaptive health care system. Our goal with this paper is to provide a methodological guide that is supported by case studies, demonstrating how futures methods can be systematically applied in health care. By offering practical examples, we intend to empower medical professionals, health care leaders, researchers, patients, and policymakers with the tools to anticipate and navigate future challenges and opportunities more effectively.
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Primary care detection of Alzheimer’s disease using a self-administered digital cognitive test and blood biomarkers

Nature Medicine, Published online: 15 September 2025; doi:10.1038/s41591-025-03965-4

A brief, self-administered digital cognitive test, in combination with a blood test, accurately detects clinical Alzheimer’s disease in primary care.
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Prognostic Value of Circulating Tumor DNA in HR+/HER2- Stage I-III Breast Cancer: A Systematic Review

Cancers (Basel). 2025 Aug 29;17(17):2831. doi: 10.3390/cancers17172831.

ABSTRACT

Background: Hormone receptor-positive (HR+), HER2-negative breast cancer accounts for the majority of breast cancer diagnoses. While outcomes have improved with neoadjuvant and adjuvant therapies, the risk of late recurrence persists, and there remains a critical need for reliable biomarkers to guide prognosis and post-treatment surveillance. Circulating tumor DNA (ctDNA), detectable via liquid biopsy, has emerged as a promising tool for monitoring minimal residual disease and predicting survival outcomes. This systematic review evaluates the association between ctDNA detection during neoadjuvant or adjuvant treatment and survival outcomes in early-stage HR+/HER2- breast cancer. Methods: This systematic review was conducted in accordance with PRISMA guidelines. A comprehensive literature search of Ovid MEDLINE and Embase was conducted to identify studies published through 3 May 2024 that evaluated ctDNA as a prognostic biomarker in stage I-III HR+/HER2- breast cancer. We included studies reporting recurrence-free survival, invasive disease-free survival, or overall survival and excluded non-original studies, conference abstracts, and non-English articles. Data extraction and qualitative synthesis were performed, and the risk of bias was qualitatively assessed across studies. No review protocol was registered. Results: Eleven studies comprising 1644 patients met the inclusion criteria. In the neoadjuvant setting, ctDNA positivity prior to treatment initiation was associated with inferior survival outcomes. In the adjuvant setting, detection of ctDNA during or after treatment was consistently linked to poorer recurrence-free and invasive disease-free survival. Across studies, ctDNA detection was a significant negative prognostic marker. Conclusions: This systematic review supports the prognostic value of ctDNA in HR+/HER2- early-stage breast cancer. Limitations include small sample sizes, observational study designs, and heterogeneity in ctDNA assays. Standardization of ctDNA testing methods and further prospective trials are needed to validate its clinical utility and explore its potential role in guiding therapeutic interventions.

PMID:40940926 | PMC:PMC12427406 | DOI:10.3390/cancers17172831

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Functions of the global health system in a new era

Nature Medicine, Published online: 11 September 2025; doi:10.1038/s41591-025-03936-9

In an irrevocably changed landscape, reform of the global health system needs to answer key questions on functions, what should be delivered in different contexts and at different levels, and how the system should operate.
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Interventions Based on Biofeedback Systems to Improve Workers’ Psychological Well-Being, Mental Health, and Safety: Systematic Literature Review

Background: In modern, high-speed work settings, the significance of mental health disorders is increasingly acknowledged as a pressing health issue, with potential adverse consequences for organizations, including reduced productivity and increased absenteeism. Over the past few years, various mental health management solutions, such as biofeedback applications, have surfaced as promising avenues to improve employees’ mental well-being. However, most studies on these interventions have been conducted in controlled laboratory settings. Objective: This review aimed to systematically identify and analyze studies that implemented biofeedback-based interventions in real-world occupational settings, focusing on their effectiveness in improving psychological well-being and mental health. Methods: A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched PubMed and EBSCO databases for studies published between 2012 and 2024. Inclusion criteria were original peer-reviewed studies that focused on employees and used biofeedback interventions to improve mental health or prevent mental illness. Exclusion criteria included nonemployee samples, lack of a description of the intervention, and low methodological quality (assessed using the Physiotherapy Evidence Database [PEDro] checklist). Data were extracted on study characteristics, intervention type, physiological and self-reported outcomes, and follow-up measures. Risk of bias was assessed, and VOSviewer was used to visualize the distribution of research topics. Results: A total of 9 studies met the inclusion criteria. The interventions used a range of delivery methods, including traditional biofeedback, mobile apps, mindfulness techniques, virtual reality, and cerebral blood flow monitoring. Most studies focused on breathing techniques to regulate physiological responses (eg, heart rate variability and respiratory sinus arrhythmia) and showed reductions in stress, anxiety, and depressive symptoms. Mobile and app-directed interventions appeared particularly promising for improving resilience and facilitating recovery after stress. Of the 9 studies, 8 (89%) reported positive outcomes, with 1 (11%) study showing initial increases in stress due to logistical limitations in biofeedback access. Sample sizes were generally small, and long-term follow-up data were limited. Conclusions: Biofeedback interventions in workplace settings show promising short-term results in reducing stress and improving mental health, particularly when incorporating breathing techniques and user-friendly delivery methods such as mobile apps. However, the field remains underexplored in occupational contexts. Future research should address adherence challenges, scalability, cost-effectiveness, and long-term outcomes to support broader implementation of biofeedback as a sustainable workplace mental health strategy.
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The Impact of Artificial Intelligence on Lung Cancer Diagnosis and Personalized Treatment

Int J Mol Sci. 2025 Aug 31;26(17):8472. doi: 10.3390/ijms26178472.

ABSTRACT

Lung cancer is the leading cause of cancer mortality globally, despite the advancements in screening and management. Survival rates for lung cancer remain suboptimal, largely due to late-stage diagnoses and tumor heterogeneity. Recent advancements in artificial intelligence and radiomics provide a promising outlook for lung cancer screening, diagnosis, personalized treatment, and prognosis. These advances use large-scale clinical and imaging datasets that help identify patterns and predictive features that may be missed by human interpretation. Artificial intelligence tools hold the potential to take clinical decision-making to another level, thus improving patient outcomes. This review summarizes current evidence on the applications, challenges, and future directions of artificial intelligence (AI) in lung cancer care, with an emphasis on early diagnosis and personalized treatment. We examine recent developments in AI-driven approaches, including machine learning and deep neural networks, applied to imaging (radiomics), histopathology, biomarker analysis, and multi-omic data integration. AI-based models demonstrate promising performance in early detection, risk stratification, molecular profiling (e.g., programmed death-ligand 1 (PD-L1) and epidermal growth factor receptor (EGFR) status), and outcome prediction. These tools may enhance diagnostic accuracy, optimize therapeutic decisions, and ultimately improve patient outcomes. However, significant challenges remain, including model heterogeneity, limited external validation, generalizability issues, and ethical concerns related to transparency and clinical accountability. AI holds transformative potential for lung cancer care but requires further validation, standardization, and integration into clinical workflows. Multicenter collaborations, regulatory frameworks, and explainable AI models will be essential for successful clinical adoption.

PMID:40943394 | PMC:PMC12429163 | DOI:10.3390/ijms26178472

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