Predictive models in healthcare are widely published, yet few achieve routine clinical use due to gaps in methodological rigor, workflow integration, and governance. Existing guidelines primarily focus on clinical settings, with few addressing broader healthcare delivery contexts. We propose a practical framework for translating code to continuous care: Development, Implementation, And MONitoring for Dependable AI prediction model (DIAMOND). Models must be built for explicit clinical use cases, supported by interoperable data, standardized predictors, and rigorous validation with prospective designs. Translation into practice requires workflow integration, proportionate regulatory oversight of intended use, transparency, uncertainty, bias, and accountability, and continued post-deployment evaluation—testing transportability across settings, monitoring and updating for data shift and performance degradation, and assessing health-economic impact to inform iterative refinement. By systematically linking these stages, the DIAMOND framework provides a structured pathway for advancing AI predictive models from promising algorithms to dependable clinical tools.
Inflammatory bone diseases, including periodontitis, osteoporosis, and osteoarthritis, are traditionally investigated as distinct pathological entities, despite sharing common features of chronic inflammation and impaired tissue regeneration. A unifying regulatory framework that mechanistically links these conditions, however, remains largely undefined. Here, we propose mitochondrial quality control (MQC) as a unifying regulatory platform that integrates inflammatory signaling, cellular metabolic fitness, and fate determination within bone and joint microenvironments. MQC comprises coordinated processes that maintain mitochondrial homeostasis, including mitochondrial dynamics, mitophagy, biogenesis, and emerging mechanisms such as mitochondrial-derived vesicles, mitocytosis, mitochondrial unfolded protein response, and mitochondrial transfer. Disruption of these pathways amplifies oxidative stress and inflammatory cascades, promoting cellular senescence and apoptosis, thereby exacerbating bone loss and cartilage degradation. This review highlights MQC dysfunction as a shared pathological axis across inflammatory bone diseases rather than a disease-specific consequence. Importantly, we frame MQC as a programmable therapeutic platform and propose a stratified intervention paradigm, in which stage-dependent modulation of mitochondrial quality, ranging from pharmacological regulation to nanotechnology-enabled mitochondrial repair and mitochondrial transfer, may enable precision treatment. This framework positions MQC at the interface of inflammation, metabolism, and regeneration, offering a multidisciplinary perspective for the development of next-generation therapies for inflammatory bone diseases.
Women of reproductive age (WRA, 15-49 years) have elevated micronutrient requirements because of menstruation, pregnancy, and lactation and their central role in maternal and child health; however, globally comparable evidence on inadequate micronutrient intake in this population remains limited. We therefore estimated the prevalence of inadequate intake of 15 essential micronutrients among WRA across countries, regions, and time and assessed inequalities according to the sociodemographic index (SDI). Using an established probabilistic dietary modelling framework, we estimated micronutrient intake inadequacy among WRA in 185 countries from 1990 to 2018 by combining median intake estimates from the Global Dietary Database with distribution-shape estimates from nutriR and applying harmonised age- and sex-specific average requirements. Absolute and relative inequalities were assessed using the slope index of inequality and the concentration index. In 2018, vitamin E had the highest estimated prevalence of inadequate intake among WRA (77.7%; 95% UI: 38.3%, 95.0%), followed by iron (72.0%; 95% UI: 53.0%, 85.1%) and calcium (70.5%; 95% UI: 61.8%, 77.1%). More than 90% of WRA in South Asia had estimated inadequate intakes of five micronutrients. Iron inadequacy worsened between 1990 and 2018, whereas magnesium and niacin inadequacy declined. Most micronutrients had a higher prevalence of inadequate intake in lower-SDI countries, although magnesium showed the opposite pattern in 2018. These findings suggest that micronutrient intake inadequacy among WRA is widespread globally, with marked regional variation, temporal change, and substantial SDI-related inequalities, and may inform nutrition policy, intervention prioritisation, and global monitoring efforts.
T-cell receptor-engineered T (TCR-T) cell therapy stands out as an innovative and promising approach in cancer immunotherapy, particularly for the treatment of solid tumors. This therapy differs from the well-established chimeric antigen receptor (CAR)-T therapy, which has revolutionized the treatment of hematologic malignancies. TCR-T therapy holds a unique edge in its capacity to recognize and target intracellular antigens, thereby broadening the spectrum of potential tumor-specific antigens that can be harnessed for therapeutic purposes. The recent FDA approval of afami-cel for synovial sarcoma marks a significant milestone in the journey of TCR-T therapy. This approval underscores the clinical potential of TCR-T in targeting solid tumors and opens up new avenues for therapeutic interventions. However, the broader clinical translation of TCR-T therapy is constrained by several critical barriers: the inherent requirement for HLA matching, the potent immunosuppressive tumor microenvironment, antigen heterogeneity leading to immune escape, and the risk of fatal on-target/off-tumor toxicities. In this review, we delineate the distinctive mechanistic advantages of TCR-T cells and provide a comprehensive analysis of the biological and technical hurdles encountered in solid tumor treatment. We synthesize findings from recent clinical trials and evaluate emerging optimization strategies, including TCR affinity fine-tuning and combinatorial approaches to modulate the immune landscape. Addressing these challenges is essential to provide a roadmap for enhancing the efficacy and safety of TCR-T therapies, ultimately facilitating their widespread adoption to improve survival outcomes for patients with refractory solid malignancies.
Despite advancements in oncology, a significant unmet need remains for therapies that effectively target and eradicate solid tumors while overcoming resistance mechanisms and minimizing damage to healthy tissues. Oncolytic virotherapy (OVT) has emerged as a promising approach to treating solid tumors by directly lysing cancer cells and simultaneously stimulating immune responses. A diverse range of viruses have been engineered to enhance their tumor-targeting capabilities. Preclinical studies show that these oncolytic viruses can induce immunogenic cell death, remodel the tumor microenvironment, and synergize with various established therapies. Their efficacy involves diverse mechanisms, including interferon signaling, metabolic reprogramming, and epigenetic regulation. While early clinical trials demonstrate promising safety and efficacy across multiple cancers, challenges such as systemic delivery and tumor heterogeneity persist. Ongoing optimization of viral engineering and combination strategies is crucial for unlocking the full clinical potential of this approach against solid tumors. This review summarizes the current landscape of OVT, highlighting its mechanistic basis, clinical progress, and the strategic innovations needed to overcome existing barriers and fully realize its potential in oncology.
Reproductive factors across lifetime, such as age at puberty and menopause, may affect women’s health, but their associations with multimorbidity remain unknown. We combined epidemiological analyses of an observational study with Mendelian Randomization analyses to examine associations of female-specific reproductive factors and their patterns with chronic conditions and multimorbidities. In observational study, we used data of 265,346 women from the UK Biobank and constructed reproductive life patterns using sequence and cluster analysis to assess associations of reproductive patterns with the prevalence, progression, cumulative rate, and patterns of multimorbidity. Five reproductive life patterns were observed: standard sequence (46.0%), early childbearing and oophorectomy menopause (6.5%), short reproductive span with natural menopause (17.8%), early childbearing and hysterectomy menopause (11.5%), and high parity with long birth span (18.1%). Compared to women with standard sequence, those with other four patterns had higher risks of presence, progression, and rapid accumulation of multimorbidity. Multi-response Mendelian Randomization was conducted to evaluate causality between reproductive factors and multimorbidity using genetic data from UK Biobank and FinnGen study. We observed that genetically proxied age at starting oral contraceptive pills or first live birth was associated with specific multimorbidities related to cardiovascular diseases, digestive diseases, and mental disorders. Weaker or less consistent epidemiological and Mendelian randomization associations were observed with other patterns of women’s lifecourse reproductive factors. In summary, convergent evidence from epidemiological studies and Mendelian Randomization analyses supports both independent and cumulative associations between reproductive life patterns and specific multimorbidities in later life. These findings have important implications for targeted prevention strategies aimed at improving women’s health.
Newborn screening represents a critical public health strategy for preventing childhood morbidity and mortality. The introduction of tandem mass spectrometry (MS/MS) has revolutionized the screening landscape for inherited metabolic diseases, shifting the paradigm from single-disease assays to a high-throughput, integrated platform capable of detecting dozens of disorders in a single run. This review systematically outlines the applications and challenges of MS/MS in newborn screening. It begins by outlining the technical principles underlying MS/MS, highlighting its unique capacity to simultaneously quantify multiple amino acids, organic acids, and fatty acid oxidation metabolites. Then, it summarizes global implementation experiences and overviews evidence to demonstrate that MS/MS significantly enhances disease detection rates, enables early intervention, and substantially improves clinical outcomes. However, its widespread adoption introduces new challenges, such as the interpretation of false-positive results, confirmation of clinical relevance for newly screened conditions, and accompanying ethical concerns. Future directions include leveraging artificial intelligence to refine interpretive workflows, expanding the screening panel, and integrating genomic technologies with MS/MS to achieve more precise diagnosis and personalized management. This review aims to offer public health policymakers, clinicians, and laboratory specialists a comprehensive interdisciplinary overview to advance the next developmental phase of newborn screening systems.
