Nature Medicine, Published online: 03 April 2026; doi:10.1038/s41591-026-04256-2

Whole-genome phylogenetic analyses have identified a case of monkeypox virus clade IIb lineage in the Republic of the Congo and co-circulation of three clade lineages, emphasizing the importance of improved surveillance given the risk of possible recombination events in the future.

Nature Medicine, Published online: 03 April 2026; doi:10.1038/s41591-026-04302-z

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

Nature Medicine, Published online: 03 April 2026; doi:10.1038/s41591-026-04305-w

To accelerate therapeutic development and equip stakeholders with clear benchmarks, the authors outline target product profiles for therapies designed to delay or prevent the onset of clinical symptoms of Alzheimer’s disease.

npj Digital Medicine, Published online: 03 April 2026; doi:10.1038/s41746-026-02544-2

User-preference alignment with uncertainty-aware interactive rectification for liver organ and tumor segmentation and analysis from CT images

Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01138-x

Leptomeningeal metastases are a devastating complication of solid tumors; how this niche becomes pro-metastatic remains poorly understood. A study now reveals that tumor cells prime a pre-metastatic niche within the leptomeninges via exosome-derived 5-HIAA, triggering vascular leakiness and accumulation of disseminated tumor cells.

Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01145-y

Huang, Hou, Yang et al. demonstrate that leptomeningeal metastatic cells favor the formation of a premetastatic niche by remodeling the choroid plexus vasculature through the serotonin metabolite 5-hydroxyindoleacetic acid, which signals into endothelial cells through the aryl hydrocarbon receptor.

Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01141-2

Li et al. present PRET, a few-shot system for pan-cancer detection not requiring model fine-tuning, validated it in multicenter datasets and found that it outperformed existing approaches across tasks and pathologists in lymph node metastasis detection.

Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01142-1

Izar and colleagues review the insights into cancer biology gained via single-cell analyses and spatial profiling and overview the challenges and opportunities associated with the implementation of these approaches to guide clinical discovery.

Background: Generative artificial intelligence (GenAI) is increasingly used in mental health care, from client-facing chatbots to clinician-facing documentation aids. Psychotherapists’ willingness to rely on—or withhold reliance from—these tools has significant implications for care quality, yet little is known about how practicing clinicians calibrate trust and distrust in GenAI across tasks and contexts. Given that the therapeutic relationship is central to psychotherapy outcomes, understanding how GenAI intersects with this relational foundation is essential for responsible integration. Objective: This study aims to examine (1) psychotherapists’ experiences with, perceptions of, and trust or distrust in GenAI in therapeutic contexts and (2) how they perceive the role of GenAI within the therapeutic relationship and how their perceptions shape their trust and distrust in GenAI. Methods: We conducted a qualitative interview study using semistructured interviews with 18 actively practicing psychotherapists in the United States between January and May 2025. Participants were recruited through professional mailing lists, social media, and snowball sampling. Interviews (≈60 min each) were conducted via Zoom and explored psychotherapists’ experiences with, perceptions of, and trust or distrust in GenAI in therapeutic contexts. Data were analyzed using the general inductive approach, with iterative coding and team-based interpretation to identify themes. Results: Our findings show that psychotherapists’ GenAI adoption was highly individualized and contingent on maintaining professional role integrity—not merely technical oversight. Trust was sustained when GenAI operated in clinician-supervised, supportive roles for low-stakes tasks (eg, documentation and brainstorming), but diminished when control shifted, tasks involved high-stakes clinical judgment, or GenAI threatened to encroach on the authentic human connection central to therapy. Participants articulated conditions for trust that went beyond “human-in-the-loop” monitoring to include preservation of interpretive authority, ethical responsibility, and relational primacy. Distrust also extended to the broader sociotechnical ecosystem, including concerns about commercial incentives, insurance pressures, and the absence of clear organizational guidelines. Conclusions: Psychotherapists’ perspectives offer critical insights into GenAI’s current usages in their professional practices and the conditions under which they are willing to trust and distrust GenAI tools. Their experiences highlight the importance of maintaining clinician control, ensuring contextual appropriateness, and preserving the human connection central to psychotherapy. Future work should further examine how therapeutic orientation, professional experience, and client characteristics shape trust and distrust in GenAI. As GenAI becomes more embedded in mental health care, research is also needed to explore how specific GenAI system features can be responsibly designed to support clinical workflows and enhance therapeutic relationships. Organizational and policy frameworks will be essential to ensure responsible, ethically aligned, and human-centered GenAI deployment in psychotherapy.

Background: During the diagnosis and treatment of non–small cell lung cancer (NSCLC), detecting the risk of its recurrence in an early phase is still challenging. Recent studies have investigated the radiomics-based machine learning (ML) models for detecting the risk of recurrence in NSCLC. However, there is still insufficient systematic evidence to prove its efficiency. Objective: This study is designed to systematically evaluate the effectiveness of radiomics-based ML in predicting the risk of recurrence in NSCLC, aiming to provide evidence-based support for the subsequent development of scoring tools to forecast recurrence risk. Methods: For acquiring research on radiomics-based models for forecasting the risk of recurrence in NSCLC, Cochrane Library, Web of Science, PubMed, and Embase were systematically retrieved, up to October 24, 2025. Studies on analyzing the recurrence of NSCLC using radiomics-based ML were included, while those in which only texture analysis was conducted or radiomics-based ML was not constructed were excluded. The Radiomics Quality Score (RQS) was used to appraise the eligible studies. Subgroup analyses were conducted according to the variables of the model, the background of treatment, the stage of lung cancer, and the pathological type. Results: Ultimately, 30 eligible studies in total were included, covering 7964 patients with NSCLC. According to the meta-analysis, the c-index of radiomics-based ML models for forecasting the risk of recurrence in NSCLC was 0.850 (95% CI 0.834‐0.866, 95% prediction interval [PI] 0.623‐1.004) in the training set. Specifically, the pooled c-index was 0.876 (95% CI 0.853‐0.900) among the patients receiving the stereotactic body radiation therapy and 0.825 (95% CI 0.804‐0.848) among those who received surgeries combined with other adjuvant treatment regimens. The c-index of the radiomics-based ML models combined with clinical features for forecasting the risk of recurrence in NSCLC was 0.833 (95% CI 0.822‐0.854, 95% PI 0.717‐0.945) in the training set. In contrast, the c-index of radiomics-based ML models for forecasting the risk of recurrence in NSCLC was 0.878 (95% CI 0.854‐0.902, 95% PI 0.681‐1.000) in the validation set. The c-index of radiomics-based ML models combined with clinical features for forecasting the risk of recurrence in NSCLC was 0.854 (95% CI 0.830‐0.878, 95% PI 0.655‐0.992) in the validation set. The average RQS across the included studies was 27.4%, revealing methodological limitations and an absence of standardization. Conclusions: This study is the first to confirm that radiomics-based ML models effectively predict the risk of recurrence in NSCLC. This study provides evidence-based support for the subsequent development or updating of radiomics-based ML models. However, the current methodological application of radiomics remains concerning. Therefore, in the future, research should standardize the workflow for implementing radiomics-based ML and incorporate multicenter imaging data to enhance its generalizability. Trial Registration: PROSPERO CRD42025631191; https://www.crd.york.ac.uk/PROSPERO/view/CRD42025631191

Background: Extant digital multiple health behavior change interventions have shown promise in various populations; however, evidence for a broader approach among the general population is lacking. Moreover, existing interventions often contain several components but are typically assessed as a whole, meaning it remains unclear to what extent individual components contribute to intervention effects and how they may interact to influence health outcomes. Objective: This study estimates the effects of 6 components of a digital health behavior change intervention on alcohol, diet, physical activity, and smoking outcomes among individuals searching for help online. Methods: A double-blind randomized factorial trial design with 6 two-level factors was used. Adults from the general public in Sweden who were seeking help to change their behaviors were recruited through web searches and social media. Participants were eligible if they were 18 years or older and had at least one health behavior classified as unhealthy. Effects of 6 components were estimated: screening/feedback, goal-setting/planning, motivation, skills/know-how, mindfulness, and self-authored SMS text messages. Primary outcomes were weekly alcohol consumption and frequency of heavy episodic drinking, average daily fruit and vegetable consumption, weekly moderate-to-vigorous physical activity, and 4-week point-prevalence smoking. Results: A total of 5419 individuals were randomized. Overall, the screening/feedback component was the most effective for changing health behaviors, along with goal-setting/planning and motivation to change. In particular, there was evidence that screening/feedback increased average daily portions of fruit and vegetables at 2 months (mean difference 0.17, compatibility interval [CoI] 0.09-0.25, probability of effect [POE] >99.9%) and at 4 months (mean difference 0.13, CoI 0.04-0.21, POE 99.9%) and reduced the frequency of heavy episodic drinking at 4 months (incidence rate ratio 0.91, CoI 0.81-1.03, POE 94.2%). Components also interacted to further improve health outcomes, most notably the combination of screening/feedback with motivation to change, which further increased fruit and vegetable consumption (2 months: mean difference 0.20, CoI 0.09-0.30, POE >99.9%; 4 months: mean difference 0.17, CoI 0.05-0.29, POE 99.8%). Conclusions: The results from this study contribute to the development of more effective interventions by providing novel insights into the effects of individual and pairwise components of complex digital health behavior change interventions. Trial Registration: ISRCTN Registry ISRCTN16420548; http://www.isrctn.com/ISRCTN16420548

Background: Artificial intelligence (AI) is increasingly integrated into education and health care, raising questions about how students use these technologies and how AI influences their learning. In health education, understanding these trends is particularly important because student learning directly impacts future clinical skills. Objective: This study aimed to explore the use of AI tools by health sciences students at the University of Ottawa. More specifically, it sought to identify the most frequently used AI tools, describe students’ usage habits, determine which tools support knowledge acquisition and skill development, and gather students’ recommendations for effective strategies to raise awareness and train their peers on the responsible use of AI. Methods: A qualitative approach was used with students from 10 health professions who reported using AI in their studies. Data were collected through semistructured interviews and an open-ended qualitative online survey. Inductive thematic analysis within an interpretive paradigm was applied to capture patterns, perceptions, and emergent themes. Results: A total of 51 health professions students participated in the study. Most were women between the ages of 20 and 29 years. ChatGPT (OpenAI) emerged as the most frequently used AI tool. Students perceived AI as a complementary tool that facilitated knowledge acquisition, skill development, writing, and problem-solving. AI adoption was driven by curiosity, peer influence, and the desire to improve work efficiency. Students critically evaluated AI results, integrated the tools into their learning processes, and emphasized the importance of technical skills, critical thinking, and digital literacy. Peer learning, hands-on demonstrations, and access to online resources were recommended for effective AI training. Conclusions: This research demonstrates that health professions students actively use AI tools, particularly ChatGPT, to support learning, skill development, and academic tasks. Although AI is valuable as an educational aid and its use varies by student and context, this highlights the need for structured guidance, critical evaluation skills, and peer-supported training. These findings highlight the importance of thoughtfully integrating AI into educational programs to enhance learning outcomes, foster skill acquisition, and ensure responsible and effective adoption.

Background: There are ongoing efforts to collect larger and higher-quality amounts of occupational health and safety data to better understand and prevent injuries and fatalities among high-risk workers, such as firefighters. Digital health systems including wearable technologies, mobile apps, or internet-based data collection platforms could collect large amounts of sensitive data, but there is little evidence on worker and employer perspectives on data privacy in the fire service. Objective: Our study examined firefighters’ and fire service leadership’s preferences regarding occupational health and safety data privacy. Methods: We conducted interviews and focus groups with career firefighters in Maryland and Virginia; interviews with union representatives and department-level leaders in each state; and interviews with national-level fire service leaders in advocacy, government, and research organizations (March to November 2023). Interviews and focus groups were audio recorded and transcribed. We analyzed transcripts using thematic analysis. Results: The sample included 31 career firefighters, 2 union leaders, 11 national leaders, and 21 department-level leaders (65 total participants from 35 interviews and 4 focus groups). We identified 4 themes: acceptability of data access, sharing, and reporting practices; data sharing and access preferences; appropriate use of firefighter data; and the need for improved communication. Leaders described firefighters’ concerns about job loss and loss of privacy. Firefighters expressed general preferences that their data be deidentified and not shared widely, and they identified mental health data as important but particularly sensitive information. Firefighters also expressed frustration about sharing data with researchers or their departments without knowing the purpose or outcomes. Both firefighters and leaders emphasized the need for enhanced communication and translation of data for firefighters. Conclusions: Fire service leaders held more concerns about the use and sharing of occupational health and safety data than firefighters, but both groups identified ways to further safeguard firefighter data and improve communication about health and safety data. Future fire service data collection should incorporate privacy protections, such as limiting the collection of identifiable information and restricting data access. Data collection should be accompanied by clear communication about the purpose of the data collection, how firefighter data will be used and accessed, and the interpretation of the results. Future digital health interventions should integrate these data privacy protections to respect firefighter preferences and contribute to acceptability and uptake.

Science, Ahead of Print.

Science, Ahead of Print.

Nature Medicine, Published online: 02 April 2026; doi:10.1038/s41591-026-04281-1

A prespecified analysis from the SELECT trial showed that semaglutide reduces major adverse cardiovascular events by 20% compared with placebo, particularly in patients at high risk of fibrosis, as indicated by the Fibrosis-4 index.

npj Digital Medicine, Published online: 02 April 2026; doi:10.1038/s41746-026-02581-x

A robust vision language model for molecular status prediction and radiology report generation in adult-type diffuse gliomas

npj Digital Medicine, Published online: 02 April 2026; doi:10.1038/s41746-026-02572-y

Integrating large language models for enhanced predictive analytics in healthcare

Cell Death Discovery, Published online: 02 April 2026; doi:10.1038/s41420-026-03009-x

Correction: The cytotoxicity of gomesin peptides is mediated by the glycosphingolipid pathway and lipid-cholesterol interactions

Cell Death Discovery, Published online: 02 April 2026; doi:10.1038/s41420-026-03031-z

Excessive pyroptosis mediates the exacerbation of pneumonia caused by low-lethality influenza virus and secondary MRSA co-infection