Hepatocellular carcinoma (HCC), one of the most common malignancies worldwide, poses a major threat to the global health. Its prognosis depends heavily on early detection. Currently, alpha-fetoprotein (AFP) is the widely used biomarker for HCC diagnosis. Nevertheless, approximately 40% of the HCC cases do not produce AFP. It has been reported that the downregulation of miR-122 is strongly associated with the development and progression of HCC. Here, employing miR-122 as a biomarker, we developed a cascade amplification-based CRISPR-Dx platform for HCC diagnosis. Owing to the strong trans-cleavage activities of Cas13a and Cas12a, the proposed assay enabled sensitive miR-122 detection down to 1 aM. Clinical sample analysis (n = 48) demonstrated a sensitivity of 91.3%, a specificity of 84.0%, and an overall accuracy of 87.5%, which is significantly better than that of the conventional AFP-based diagnosis (sensitivity, 43.5%; specificity, 80%; accuracy, 62.5%). In addition, because CRISPR-Dx eliminates the RNA extraction and reverse transcription steps that may cause target loss, it also showed better performance than miR-122-targeted qPCR. Given its high diagnostic accuracy and simplified workflow, the proposed miR-122-based CRISPR-Dx assay holds great promise for the clinical diagnosis of HCC.

Recent reports suggest that peri-immune checkpoint inhibitor (ICI) COVID-19 mRNA vaccination may improve survival in lung cancer, but time-related and calendar-time biases may inflate real-world estimates. We evaluated vaccination timing and outcomes using a target trial emulation-informed, time-aligned design.

This retrospective cohort study used deidentified electronic health record data from the TriNetX Global Collaborative Network. Time zero was first ICI administration. New users initiating ICI therapy from September 2, 2020, through December 31, 2025, were classified by mRNA vaccination within -100 to +100 days as peri-ICI, pre-only, post-only, or none. Follow-up began at a prespecified day-100 landmark. Cohorts were balanced using 1:1 propensity score matching. Endpoints were overall survival (OS) and time to next systemic treatment or death (TTNT-D).

After matching, 2,286 patients were included per group (4,572 total). Peri-ICI mRNA vaccination was not associated with OS (hazard ratio [HR] 1.005, 95% confidence interval [CI] 0.913-1.106) or TTNT-D (HR 1.059, 95% CI 0.956-1.174). The pre-only versus post-only OS estimate was near null (HR 0.920, 95% CI 0.804-1.053), with concordant patterns across prespecified sensitivity analyses.

Peri-ICI COVID-19 mRNA vaccination was not associated with improved outcomes in patients with lung cancer. These findings clarify discrepant reports and underscore the importance of rigorous time alignment when evaluating time-dependent exposures.

Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is increasingly recognized as a disorder with developmental origins, yet its early neuroendocrine antecedents during puberty remain poorly understood. While most diagnostic frameworks apply post-menarche, growing evidence suggests that PMOS risk may be programmed well before clinical onset through alterations in central neuroendocrine pathways that emerge during the pubertal transition. In this review, we examine the concept of pubertal neuroendocrine programming in girls at risk for PMOS, with a particular focus on kisspeptin-GnRH dysregulation, central metabolic signaling, and the emerging role of oxytocin in modulating reproductive and behavioral outcomes. We propose that early disturbances in the integration of reproductive, metabolic, and social neuroendocrine circuits contribute to the trajectory toward PMOS. Special attention is given to the "social brain," including oxytocinergic pathways, which may influence stress sensitivity, emotional eating, and pubertal tempo; underexplored but potentially modifiable dimensions of PMOS risk. By synthesizing data from basic science, translational models, and adolescent cohorts, we outline neuroendocrine signatures of early PMOS vulnerability and evaluate their potential as biomarkers and therapeutic targets. Finally, we discuss opportunities for intervention during the pubertal window, including lifestyle, behavioral, and central nervous system-targeted therapies. Understanding how the brain orchestrates puberty in at-risk individuals may unlock new strategies for preventing PMOS before it fully manifests, shifting the clinical focus from late diagnosis to early modulation.

In a recent issue of Nature, Desharnais and colleagues show that diet-dependent remodeling of the gut microbiome promotes anti-tumor immunity and may explain the enhanced efficacy of immune checkpoint blockade observed in obesity. Their study identifies dietary intervention as a promising strategy to optimize the host for cancer immunotherapy.

DICER1-related tumor predisposition is an autosomal dominant disorder predisposing to a broad spectrum of malignant and benign neoplasms, caused by germline pathogenic variants (PVs) in the DICER1 gene. We aimed to characterize the clinical features of DICER1-related tumor predisposition in a national referral cohort and to estimate neoplasm risk.

This retrospective study was conducted in a cohort of 945 patients who underwent DICER1 genetic testing at Institut Curie, Paris, using Sanger sequencing from 2012 to 2014 and Next Generation Sequencing from 2015 to 2023.

Among 584 index cases evaluated for DICER1-related tumor predisposition, 91 (16%) carried a germline DICER1 PV and 31 (5%) harbored only somatic DICER1 PVs. Several tumors that were not previously part of the DICER1 tumor spectrum were identified. ETMR-like brain tumor and testicular Sertoli cell tumor are now recognized as DICER1-related neoplasms, and schwannoma is a strong candidate. The neoplasm risk was estimated in 170 relatives carrying a germline DICER1 PV. The cumulative incidence of malignant neoplasms was 4.8% [95% CI: 2.1% - 9.1%] at 10 years and 15.8% [95% CI: 8.9% - 24.7%] at 50 years. Overall neoplasm risk was significantly higher in females, primarily driven by the higher incidence of thyroid follicular nodular disease.

This large cohort study provides a comprehensive overview of the distribution of neoplasms associated with DICER1-related tumor predisposition. Broader genetic testing identified additional DICER1-related neoplasms, and schwannoma emerged as a candidate association. Finally, this study confirms the moderate penetrance of germline DICER1 PVs.

The Tasmanian devil (Sarcophilus harrisii) population has undergone a major decline in the wild owing to the epidemics of two transmissible cancers known as devil facial tumours (DFT1 and DFT2). A multipronged conservation strategy is in place, but a vaccine that prevents devils from developing devil facial tumour disease would be a major step towards recovering the wild devil population. Critical to an effective DFT vaccine are target antigens. Putative non-coding regions of genomes have been identified as potential tumour-specific antigens for human cancer. These non-coding regions include long terminal repeats (LTRs) of endogenous retroviral elements (ERVs). We identified 11 193 ERV LTR transcripts that were expressed in DFT1 or DFT2 transcriptomes but not in healthy tissue samples. Using a proteogenomic approach, we identified 33 ERV LTR peptides unique to DFT1 and/or DFT2 immunopeptidomes; five of these were validated in subsequent screens with synthetic peptides. The ERV LTR peptides identified in this study can be tested as vaccine targets in DFT1 and DFT2 vaccines. This method can be applied to other species for the development of cancer vaccine targets that may be shared across tumour types.

The time burden among patients with cancer is prominent, disrupting daily routines, inducing emotional distress, and adversely affecting patients' quality of life and treatment adherence. However, existing research on this topic remains fragmented and lacks a comprehensive synthesis. This scoping review was conducted to systematically synthesize published evidence on time toxicity among patients with cancer, providing a research reference for subsequent investigations in this field.

We systematically searched 6 electronic databases from inception to February 1, 2026, for articles published in English: PubMed, Web of Science, Embase, CINAHL, Scopus, and Cochrane Library. The search terms focused on key concepts including cancer and time toxicity. All retrieved literature was synthesized into four major categories: current status, influencing factors, assessment methods of time toxicity, and corresponding intervention measures.

A total of 30 articles were included in the final review. Patients may experience notable time toxicity, which appears to be influenced by demographic and socioeconomic/insurance factors, disease-related factors, treatment-related factors and other relevant factors. At present, various methods have been developed to assess time toxicity, and relevant interventions are available to reduce patients' time toxicity.

Patients with cancer may experience notable time toxicity, which appears to be influenced by multiple factors. Targeted interventions for different populations may warrant further development in future research. Current measurement methods can help assess patients' time toxicity, although further optimization is needed to improve the accuracy and comprehensiveness of relevant assessments. This issue merits further exploration in subsequent studies.

Airway complications remain a significant cause of morbidity after lung transplantation. Among them, vanishing bronchus syndrome (VBS) represents a severe form of airway injury characterized by progressive distal bronchial stenosis. Although ischemia has been implicated in its pathogenesis, the role of airway colonization with multidrug-resistant organisms remains incompletely understood.

We conducted a retrospective, single-center study of lung transplant recipients who developed VBS between January 2001 and November 2025. Clinical characteristics, bronchoscopic findings, microbiological data, and outcomes following airway stenting were reviewed. VBS was defined as progressive bronchial stenosis predominantly involving the distal airway beyond the bronchial anastomosis. Associations between airway infection, stent outcomes, and airway healing were evaluated.

Among 203 lung transplant recipients, five patients (2.5%) developed VBS requiring airway stenting. All patients demonstrated stenosis involving the bronchus intermedius. Multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus, were detected in two patients, both of whom remained stent-dependent. In contrast, three patients without multidrug-resistant organisms ultimately achieved successful stent removal with sustained airway patency. However, long-term stent dependency was also influenced by persistent structural airway abnormalities and stent-related factors.

VBS may involve a complex interplay among ischemic injury, structural airway abnormalities, stent-related factors, and microbial colonization. Persistent multidrug-resistant airway colonization may be associated with unfavorable airway outcomes; however, its independent contribution remains uncertain.

To assess the implementation of the “Renewal of treatment for allergic rhino-conjunctivitis by community pharmacists” cooperation protocol in a multiprofessional medical home using four indicators—usefulness, efficiency, safety, and satisfaction—six months after implementation.

The intervention was carried out between April and November 2023. General practitioners and pharmacists/pharmacy assistants were invited to participate in the protocol. Inclusion criteria for patients were being between 15 and 50 years old, followed by a general practitioner affiliated with the medical home, and having a diagnosis of allergic rhinitis with a corresponding medication prescription. Usefulness was assessed as the proportion of patients managed by delegated professionals; efficiency, as the proportion of patients for whom the delegating general practitioner resumed follows-up; safety, as the occurrence of adverse events; and satisfaction, as assessed among professionals and patients.

Nine delegating general practitioners and 12 delegated pharmacists/pharmacy assistants participated in the protocol. Thirty-one patients were included and followed. Indicator results were 42.8% (usefulness), 87.1% (efficiency), 100% (safety), and 100% (satisfaction). Implementation of the protocol was limited in scope and by the complexity of administrative follow-up.

The protocol “Renewal of treatment for allergic rhino-conjunctivitis in pharmacies” is feasible and should be maintained, with consideration given to simplifications.

Introduction : The COVID-19 crisis and successive lockdowns profoundly altered the epidemiology of mental health and patterns of care delivery. Methods : This study aims to identify the profiles of patients newly receiving care for psychiatric disorders during the health crisis, to analyze changes in their trajectories and care pathways throughout the lockdown periods, and to compare them with individuals who were already receiving care prior to the pandemic. It also seeks to better understand triggering factors, mobilized resources, patterns of healthcare utilization, and coordination between professionals and care structures. A mixed-methods approach was used: A quantitative analysis of data from the French National Health Data System (SNDS) (2016–2021) to identify profiles of mental healthcare utilization. A qualitative analysis based on 29 interviews with individuals aged 18–24 and 50–64 who experienced psychological disorders before and/or during the health crisis. Results : The crisis had age-specific impacts: young people were more frequently hospitalized, whereas individuals aged 50–64 showed higher use of psychotropic medications. However, these trends conceal considerable heterogeneity in care trajectories, ranging from episodic care to long-term follow-up. Interviews reveal that the crisis acted as a catalyst for psychological disorders and social vulnerabilities, particularly among young adults but also among those aged 50–64. Discussion : The results show both a reorganization of care provision and healthcare utilization during the pandemic, as well as a diversity of trajectories shaped by age, prior medical history, and available resources. Moreover, the onset of disorders and engagement with care pathways do not always coincide with periods of strict lockdown. Conclusion : The health crisis highlighted, and often amplified, latent psychological and social vulnerabilities within the population.