No abstract

The tumor immune microenvironment (TIME) is closely associated with tumor formation, particularly linked to the human papillomavirus (HPV), and regulates tumor initiation, proliferation, infiltration, and metastasis. With the rise of immunotherapy, an increasing amount of sample data used for TIME exploration is available in databases. However, no currently available web tool enables a comprehensive exploration of the TIME of HPV‐associated cancers by leveraging these data. We have developed a web tool called HPV‐associated Tumor Immune MicroEnvironment ExploreR (HPVTIMER), which provides a comprehensive analysis platform that integrates over 10,000 genes and 2290 tumor samples from 65 transcriptome data sets across 8 cancer types sourced from the Gene Expression Omnibus (GEO) database. The tool features four built‐in analysis modules, namely, the differential expression analysis module, correlation analysis module, immune infiltration analysis module, and pathway analysis module. These modules enable users to perform systematic and vertical analyses. We used several analytical modules in HPVTIMER to briefly explore the role of CDKN2A in head and neck squamous cell carcinomas. We expect that HPVTIMER will help users explore the immune microenvironment of HPV‐associated cancers and uncover potential immune regulatory mechanisms and immunotherapeutic targets. HPVTIMER is available at http://www.hpvtimer.com/.

Background The burden of elderly cardiovascular disease (CVD) has received increasing attention with population aging worldwide. Aims We reported on the global CVD burden in elderly individuals over 70, 1990-2019. Methods and Results Based on the Global Burden of Disease Study 2019, elderly CVD burden data were analysed. Temporal burden trends were analysed with the joinpoint model. The slope index and concentration index were used to evaluate health inequality. From 1990 to 2019, the global elderly CVD incidence, prevalence, death, and disability-adjusted life year (DALY) rates generally decreased. However, the current burden remains high. The rapid growth in burden in parts of Sub-Saharan Africa and Asia is a cause for concern. Countries with a higher socio-demographic index (SDI) have generally seen a greater decrease in burden, while countries with a lower SDI have generally experienced increases or smaller declines in burden. Health inequality analysis confirmed that the burden was gradually concentrating towards countries with a low SDI. Among the different CVDs, ischaemic heart disease causes the greatest burden in elderly individuals. Most CVD burdens increase with age, but stroke and peripheral vascular disease show markedly different distributional characteristics. In addition, the burden of hypertensive heart disease shows an unusual shift towards high SDI countries. High systolic blood pressure was consistently the leading risk factor for CVD among elderly individuals. Conclusion The burden of CVD in older people remains severe and generally tends to shift to lower SDI countries. Policymakers need to take targeted measures to reduce its harm.

<b><i>Background:</i></b> Meningitis is a severe and fatal neurological disease and causes lots of disease burden. The purpose of this study was to assess the global, regional, and national burdens and trends of meningitis by age, sex, and etiology. <b><i>Methods:</i></b> Data on the burden of meningitis were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. R and Joinpoint were used for statistical analysis and charting. <b><i>Results:</i></b> In 2019, meningitis caused 236,222 deaths and 15,649,865 years of life lost (YLL) worldwide. The age-standardized death rate and age-standardized YLL rate of meningitis were 3.29 and 225, which decreased steadily. Burden change was mainly driven by epidemiological changes. Regionally, meningitis burden was the highest in Sub-Saharan Africa. Burden of disease increasingly concentrated in low sociodemographic index countries, and this was most pronounced in meningitis caused by <i>N. meningitidis</i>. Countries such as Mali, Nigeria, Sierra Leone, etc., especially need to enhance the rational allocation of public health resources to reduce the disease burden. Children and men were more likely to be affected by meningitis. PM2.5 was found to be an important risk factor. <b><i>Conclusions:</i></b> This study provides the first comprehensive understanding of the global disease burden of meningitis caused by specific pathogens and highlights policy priorities to protect human health worldwide, with particular attention to vulnerable regions, susceptible populations, environmental factors, and specific pathogens.

Lacking appropriate model impedes basic and preclinical researches of brain tumors. Organoids technology applying on brain tumors enables great recapitulation of the original tumors. Here, we compared brain tumor organoids (BTOs) with common models including cell lines, tumor spheroids, and patient‐derived xenografts. Different BTOs can be customized to research objectives and particular brain tumor features. We systematically introduce the establishments and strengths of four different BTOs. BTOs derived from patient somatic cells are suitable for mimicking brain tumors caused by germline mutations and abnormal neurodevelopment, such as the tuberous sclerosis complex. BTOs derived from human pluripotent stem cells with genetic manipulations endow for identifying and understanding the roles of oncogenes and processes of oncogenesis. Brain tumoroids are the most clinically applicable BTOs, which could be generated within clinically relevant timescale and applied for drug screening, immunotherapy testing, biobanking, and investigating brain tumor mechanisms, such as cancer stem cells and therapy resistance. Brain organoids co‐cultured with brain tumors (BO‐BTs) own the greatest recapitulation of brain tumors. Tumor invasion and interactions between tumor cells and brain components could be greatly explored in this model. BO‐BTs also offer a humanized platform for testing the therapeutic efficacy and side effects on neurons in preclinical trials. We also introduce the BTOs establishment fused with other advanced techniques, such as 3D bioprinting. So far, over 11 brain tumor types of BTOs have been established, especially for glioblastoma. We conclude BTOs could be a reliable model to understand brain tumors and develop targeted therapies.