Deep cell phenotyping and spatial analysis of multiplexed imaging with TRACERx-PHLEX.

The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations. PHLEX was developed using imaging mass cytometry (IMC) in the TRACERx study, validated using published Co-detection by indexing (CODEX), IMC and orthogonal data and benchmarked against state-of-the-art approaches. We evaluated its use on different tissue types, tissue fixation conditions, image sizes and antibody panels. As PHLEX is an automated and containerised Nextflow pipeline, manual assessment, programming skills or pathology expertise are not essential. PHLEX offers an end-to-end solution in a growing field of highly multiplexed data and provides clinically relevant insights.

Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer.

Understanding the role of the tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs in treatment-naïve early-stage lung cancer using imaging mass cytometry in the TRACERx study (n = 81 patients/198 samples/2.3 million cells). In immune-hot adenocarcinomas, spatial niches of T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for niches of plasma and B cells in immune-excluded squamous cell carcinomas (LUSC). Immune-low TMEs were associated with fibroblast barriers to immune infiltration. The fourth archetype, characterized by sparse lymphocytes and high tumor-associated neutrophil (TAN) infiltration, had tumor cells spatially separated from vasculature and exhibited low spatial intratumor heterogeneity. TAN-high LUSC had frequent PIK3CA mutations. TAN-high tumors harbored recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune, and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis. SIGNIFICANCE: This study provides novel insights into the spatial organization of the lung cancer TME in the context of tumor immunogenicity, tumor heterogeneity, and cancer evolution. Pairing the tumor evolutionary history with the spatially resolved TME suggests mechanistic hypotheses for tumor progression and metastasis with implications for patient outcome and treatment. This article is featured in Selected Articles from This Issue, p. 897.

Advancing diabetes primary care education and knowledge in Nepal: A scoping review and case study discussion.

AIMS: Diabetes mellitus (DM) is a chronic disorder of insulin and glucose metabolism. It affects more than 463 million people worldwide and is expected to reach 700 million by 2045. In the Southeast Asian region, the prevalence of DM has tripled to 115 million due to rapid urbanization, unhealthy diet, sedentary lifestyles, and genetic factors. In Nepal, a developing country, DM affects 8.5% of adults, with an alarming increase in recent years. Lack of diabetes education and limited populational adoption of behavioural changes further hamper care. METHODS: In the present study, we performed a scoping review to determine the status of awareness, attitudes, and knowledge about diabetes in the Nepalese population with a focus on the educational initiatives that have been implemented. We also conducted a two-week international case study discussion among medical students to brainstorm viable intervention strategies. RESULTS: Our findings indicate that limited data is available on the level of education or initiatives to improve knowledge and practice among healthcare professionals and community members. Targeted studies of people with diabetes also present heterogeneous results due to differences in the sample population, geographic location, education, age, and gender. Accordingly, we propose five interrelated education-based strategies that leverage existing networks to expand community outreach and engagement, improve system resilience, and improve health outcomes. CONCLUSIONS: Effective education for healthcare professionals, community, and patients with diabetes is vital in improving diabetes outcomes in Nepal and South Asia. Collaboration, funding, and evaluation are key areas needing reform.

Combating malaria in Kenya through collaborative population health education: a systematic review and pilot case study.

BACKGROUND: Malaria continues to be a public health problem in Kenya, with an estimated 37.2 million people at high risk of the disease. The disease burden is compounded by inequalities in health service availability, housing, socioeconomic conditions, and access to education. OBJECTIVES: We aimed to determine the status of community-based, health education interventions. Based on the findings, to develop an educational module for medical students to combat malaria in Kenya. METHODS: A systematic review was conducted to identify different educational interventions, their successes and limitations, and legal challenges leading to low uptake and adherence to malaria prevention interventions from 2000-2023. Consequently, a 6-week online educational pilot was conducted with healthcare students from Kenya, Japan, the UK, and Cyprus. RESULTS: Despite developing a national malaria strategy and monitoring and evaluation strategies, Kenya has not been able to meet the incidence reduction targets set by the World Health Organisation, underscoring the need for more work in identifying the barriers to implementing strategies and optimising the distribution of public health interventions. Student teams proposed innovative solutions, including two-tier malaria control strategies, maternal malaria clinical education, community awareness through schools and NGOs, and a 10-year health system strengthening and immunisation plan. CONCLUSIONS: Public education regarding prevention strategies and increasing their adoption remains a key challenge in combating malaria in Kenya. In this regard, digital tools can facilitate international collaborative health education and exchange of best practices, allowing students and faculty to engage across boundaries and prepare them to be future-ready physicians connected to the global community.

Mental Health Support for the Current and Future Medical Professionals during Pandemics.

Psychological distress among medical professionals due to the novel coronavirus disease 2019 (COVID-19) pandemic is of great concern as it may lead to mental health problems and, furthermore, work leaves. Studies suggest that immediate psychological interventions are needed to protect medical staff during this chaotic situation. However, the importance of mental healthcare for the "future" medical staff, such as medical students, remains underestimated compared with that of current medical professionals. Medical students also face potential mental health stressors during their degrees and clinical clerkships, further increasing the risk of their psychological disorders. Hence, they should also be protected from burnout by various measures at governmental, organizational, and individual levels. To maintain a sustainable, robust healthcare system, medical professionals, students, and society should unite and collaboratively overcome the hardships of the COVID-19 pandemic.