The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Dipeptidyl peptidase-1 (DPP1) inhibitors prevent the activation of neutrophil serine proteases and reduce exacerbations in people with bronchiectasis. We previously identified a novel effect of DPP1 inhibitors in reducing the neutrophil pseudoenzyme azurocidin-1 (AZU1). The aim of this study was to investigate the role of AZU1 in the pathophysiology of bronchiectasis. Sputum AZU1 concentrations were analysed in multiple cohorts. These consisted of two observational cohorts of patients with bronchiectasis (EMBARC BRIDGE cohort 1 and cohort 2) and a cohort of patients with chronic obstructive pulmonary disease (COPD; TARDIS COPD cohort) to correlate AZU1 with disease severity and exacerbations. A rhinovirus challenge study was used to investigate AZU1 concentrations during experimental exacerbation in COPD, people who smoke, and controls. A post-hoc analysis of the phase 2 WILLOW trial of brensocatib versus placebo was used to assess the effect of DPP1 inhibition on airway AZU1. Higher AZU1 sputum concentration was associated with increased bronchiectasis disease severity index (p<0·0001), decreased percentage predicted forced expiratory volume in 1 second (r=-0·4662, p<0·001), and increased exacerbation frequency (p<0·0019; EMBARC cohort 1, n=197). AZU1 was associated with radiological severity (Reiff score), symptoms (quality of life bronchiectasis respiratory symptom score), and bacterial infection (sputum microbiology and 16S microbiome alpha diversity; highest levels of AZU1 were found in airway samples with Pseudomonas aeruginosa; p<0·0001; EMBARC cohort 2, n=144). Bronchiectasis patients with bacterial and viral exacerbations had increased concentrations of AZU1 (p=0·0003; n=96). These findings were extended to COPD, in which AZU1 was related to COPD severity (COPD cohort, n=101), and in patients with COPD challenged with rhinovirus A16, AZU1 was increased at day 9 post-challenge (p<0·001; n=9). In-vitro AZU1 impaired ciliary function and epithelial integrity, suggesting a mechanism by which AZU1 drives disease pathogenesis. In a post-hoc analysis of the WILLOW trial, AZU1 was the most downregulated protein with brensocatib treatment (brensocatib 10 mg, n=71; brensocatib 25 mg, n=73; and placebo, n=71). Over 24 weeks, AZU1 was significantly reduced by DPP1 inhibition (p<0·0001). AZU1 was identified as a novel marker of disease severity in bronchiectasis, associated with bacterial infection and exacerbation, and targeted by DPP1 inhibition. EMBARC3 and Insmed.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1·3 billion (95% uncertainty interval [UI] 1·2 to 1·4) individuals were estimated to be living with MASLD (ie, 16·1% of the global population), with an age-standardised prevalence rate of 14 429·3 (95% UI 13 268·3 to 15 990·6) per 100 000 population, representing a percentage increase of 142·7% (95% UI 139·2 to 146·7) in crude numbers from 1990 (0·5 billion [0·5 to 0·6]) and of 28·6% (27·8 to 29·5) in the rate (11 217·2 [10 276·8 to 12 467·0] per 100 000 in 1990). An estimated 3·6 million (2·8 to 4·5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39·6 (31·2 to 49·9) per 100 000 population. Despite a 116·3% (93·3 to 139·4) increase in crude DALYs (from 1·7 million [1·3 to 2·1] in 1990), its age-standardised estimate remained consistent (1·8% [-8·6 to 12·8]) from 1990 (38·9 [30·1 to 49·8] per 100 000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29 246·1 [26 848·3 to 32 048·7] per 100 000) and Andean Latin America showed the highest DALY rate (152·3 [114·1 to 194·7] per 100 000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653·5 [7923·7 to 9592·8] per 100 000) and east Asia had the lowest DALY rate (16·3 [13·5 to 19·9] per 100 000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15 616·4 [14 349·2 to 17 263·3] per 100 000 people in 2023) than in females (13 245·2 [12 132·0 to 14 692·6] per 100 000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2·2 [95% UI 1·6 to 3·1] per 100 000 people), followed by high BMI (1·4 [0·6 to 2·4] per 100 000 people) and smoking (1·0 [0·3 to 1·8] per 100 000 people). Our forecasting model estimates that 1·8 billion (95% UI 1·6 to 2·0) individuals are likely to have MASLD by 2050, representing a 42·0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15 774·9 (95% UI 14 613·9 to 17 336·2) per 100 000 people in 2050, representing an average annual percentage change of 0·3% (95% UI 0·3-0·3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16·1% and approximately 1·3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.
Bronchiectasis and diabetes commonly coexist and are associated with immune dysfunction and increased susceptibility to infection. Although diabetes is associated with worse prognosis in cystic fibrosis-related bronchiectasis, data are scarce for its impact on non-cystic fibrosis bronchiectasis. This study aimed to characterise the impact of diabetes on clinical outcomes and microbial and inflammatory profiles in patients with bronchiectasis. This analysis comprised data from the European Bronchiectasis Registry (EMBARC), Respiratory Research Network of India (EMBARC-India), Chinese Bronchiectasis Registry (BE-China), and Australian Bronchiectasis Registry (ABR); 30 263 patients with CT-confirmed bronchiectasis in 33 countries were included in the analysis: 16 963 from EMBARC (Jan 12, 2015, to April 12, 2022), 2361 from EMBARC-India plus additional Asian countries (June 1, 2015, to Sept 1, 2017), 10 324 from BE-China (Jan 10, 2020, to March 31, 2024), and 615 from the ABR (March 7, 2016, to Sept 11, 2018). Clinical data were compared between patients with and without diabetes. Long-term outcome data were available in EMBARC and EMBARC-India. Microbiome and inflammatory profiles were characterised in a sub-cohort of EMBARC patients by sputum 16S rRNA sequencing (n=433) and serum Olink (n=479). 2487 (8·2%) of 30 263 patients with bronchiectasis had diabetes. Patients with diabetes had a higher prevalence of comorbidities than those without diabetes, including cardiovascular disorders (53·5% vs 21·8%, p<0·0001), asthma (27·5% vs 21·0%, p<0·0001), and chronic obstructive pulmonary disease (34·3% vs 19·0%, p<0·0001). Patients with diabetes had more severe disease than those without diabetes, with higher Bronchiectasis Severity Index scores (8 [IQR 5-12] vs 7 [4-10], p<0·0001) and UK Medical Research Council (MRC) dyspnoea scores (p<0·0001) and more hospital admissions in the previous year (p<0·0001). After adjustment for confounders, outcomes were significantly worse in patients with diabetes than in those without diabetes, including more frequent exacerbations (incidence rate ratio [IRR] 1·18 [95% CI 1·09-1·28], p<0·0001), hospital admissions (IRR 1·57 [1·40-1·76], p<0·0001), and higher 5-year mortality (hazard ratio 1·80 [1·53-2·12], p<0·0001). The sputum microbiome was significantly altered in patients with diabetes compared to those without diabetes, with increased isolation of Enterobacteriaceae (p<0·0001), Moraxella catarrhalis (p=0·0035), and Haemophilus influenzae (p=0·046). In serum, Gal-4 and GDF-15, established biomarkers of disease severity and cardiovascular risk in diabetes, were significantly increased in patients with diabetes (Gal-4, p<0·0001; GDF-15, p=0·0019). Patients with diabetes and bronchiectasis are a high-risk population with more severe disease, worse outcomes, increased comorbidities, and increased risk of infections compared with patients without diabetes. These findings support inclusion of diabetes as a risk factor in individualised risk assessments for bronchiectasis. European Respiratory Society, Armata, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Grifols, Insmed, Janssen, Lifearc, Roche, Verona Pharma, Zambon, National Natural Science Foundation of China, Innovation Program of the Shanghai Municipal Education Commission, Program of the Shanghai Municipal Science and Technology Commission, Program of the Shanghai Shenkang Development Center, EU/European Federation of Pharmaceutical Industries and Associations, Innovative Medicines Initiative, and Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium.
Actinobacillus pleuropneumoniae (APP) is the etiological agent of porcine pleuropneumoniae (PP), a high contagious respiratory disease with significant impact on the swine industry in both clinically and economically. Despite of the several attempts to control APP, the emergence of novel serotypes and antimicrobial resistance (AMR) strains highlights the importance of monitoring the genetic characteristics of APP at single nucleotide level. Despite the importance of genomic surveillance of APP to develop effective control strategies, genetic information on the recent Korean isolates of APP is not available at whole genome level. Therefore, in this study, six APP strains were isolated from porcine lungs with characteristic lesions of PP from 2022 to 2024. And their whole genomic sequences, serotypes, virulence factors, and AMR traits were investigated using combined short- and long-read sequencing methods. In silico PCR serotyping identified the isolates as serotype 1, 7, and 15, while one isolate was non-typeable. Multiple AMR genes including Hinf_PBP3_BLA, Ecol_EFTu_PLV, tet(B), tet(O), tetR, sul2, aph(3'')-Ib, aph(6)-Id, and aph(3')-Ia were detected. Also, these genes were located with adjacent to mobile genetic elements, suggesting the possibility of horizontal gene transfer. Phylogenetic comparison with 40 global APP complete genomes, presented that Korean isolates were closely related with China and Switzerland strains. This study provides the whole genome sequences based genetic characterization on the recent Korean isolates of APP, and this study emphasizes that continuous monitoring of APP genomic variation to support effective control of porcine pleuropneumoniae.
Rapid and accurate detection of Mycobacterium tuberculosis complex (MTBC) in acid-fast bacilli (AFB)-positive cultures is crucial for effective patient management and transmission control. This study assessed the diagnostic performance and cost-efficiency of the Bioline MPT64 assay for detecting MTBC in AFB-positive cultures in a setting with frequent nontuberculous mycobacteria (NTM) isolation. Between August 2024 and February 2025, AFB-positive cultures were tested in parallel using the Bioline MPT64 assay and real-time polymerase chain reaction (PCR). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Bioline MPT64 assay were calculated using real-time PCR as the reference standard. Cost-efficiency of diagnostic strategies incorporating the Bioline MPT64 assay was also evaluated. Based on real-time PCR results, among 494 AFB-positive cultures, 192 (38.9%) were MTBC-positive, 299 (60.5%) were NTM-positive, 2 (0.4%) were positive for both MTBC and NTM, and 1 (0.2%) was negative for both. The Bioline MPT64 assay exhibited a sensitivity of 99.0% (192/194), specificity of 100% (300/300), PPV of 100% (192/192), and NPV of 99.3% (300/302). Two false-negative results occurred in MTBC-NTM co-positive cultures. Using the Bioline MPT64 assay alone could reduce costs by 66.7% compared to real-time PCR alone but carries a risk of missing approximately 1.0% of MTBC-positive cultures. A stepwise strategy-initial screening with the Bioline MPT64 assay followed by real-time PCR for MPT64-negative cultures-could offer diagnostic accuracy comparable to real-time PCR alone but result in only a modest 5.5% cost reduction. The Bioline MPT64 assay shows strong concordance with real-time PCR and offers substantial cost savings when used alone, though it may miss MTBC-NTM co-positive cultures. PCR confirmation of MPT64-negative results mitigates this risk but provides only modest cost savings in NTM-prevalent settings.
Two strains were isolated from riverbed soil in Paju-si, Gyeonggi-do, Republic of Korea. The strain designated as MI9T was a Gram-stain negative, strictly aerobic, rod-shaped bacterium that was motile by flagella and formed yellow colonies, while the strain designated as GY13T was a Gram-stain negative, strictly aerobic, rod-shaped, nonmotile bacterium that formed pink colonies. These two strains were classified as belonging to the genera Hydrogenophaga and Larkinella, respectively, based on phylogenetic analyses of their 16 S rRNA gene sequences and draft genomes. The strains MI9T and GY13T exhibited optimal growth at 30 °C and pH 7.0 in the presence of 0% NaCl. Strain MI9T grew within a temperature range of 10-30 °C and a pH range of 5.0-10.0, tolerating up to 1.0% NaCl. Strain GY13T grew within a temperature range of 10-35 °C and a pH range of 5.0-10.0, but only in the absence of NaCl. Comparative analysis between the strains revealed that the average nucleotide identity (ANI) values (79.2%-87.8%) and digital DNA-DNA hybridization (dDDH) values (21.6%-29.1%) of strain MI9T matched those of the genus Hydrogenophaga, while the ANI values (77.1%-94.7%) and dDDH values (19.2%-54.3%) of strain GY13T matched those of the genus Larkinella. Phylogenetic data, ANI and dDDH values, and physiological and biochemical characteristics collectively demonstrated that the strains MI9T and GY13T exhibited distinct characteristics that could distinguish them from other species within the genera Hydrogenophaga and Larkinella, respectively. We propose the names Hydrogenophaga sedimenti (type strain MI9T = KACC 24145T = TBRC 21213T) and Larkinella fluvii (type strain GY13T = KACC 24146T = TBRC 21185T), respectively.
Phytoplasmas are wall-less obligate parasites of plants and insects. Several phytoplasma strains within the Peanut Witches' Broom (PWB; 16SrII) group are associated with significant disease losses across diverse crops and weeds. We present complete, single contig genome assemblies for two Indian parthenium phyllody strains, 'Candidatus Phytoplasma asiaticum' PR34 and 'Ca. P. australasiaticum' PR08, generated through host DNA depletion and hybrid Illumina-Nanopore sequencing. Both genomes display characteristic features of reductive evolution (∼614 kb and 589 kb, respectively) but show notable differences from previously sequenced PWB phytoplasmas. In contrast to most of PMU-rich phytoplasma genomes, neither PR34 nor PR08 retains intact Potential Mobile Units. Instead, both harbor numerous open reading frames encoding group II intron reverse transcriptase/ maturase proteins, predominantly of the mitochondrial-like type, with PR34 containing 52 and PR08 28 such loci that together constitute > 4% of each genome. These observations support the hypothesis that intron-associated processes may contribute to genome variability in the absence of canonical PMUs. Comparative analyses support the classification of PR34 as a distinct species within the PWB complex and reveal both conserved Sec-dependent effectors (SAP05, SAP11, and SAP54/PHYL1) and lineage-specific secreted proteins with predicted nuclear localization. Additional retained features include functional sodA genes and multiple truncated HlyB-like transporters. Collectively, these high-quality genomes illustrate a genomic configuration in which extensive genome reduction and loss of PMUs coexist with the retention of core virulence factors and an expanded repertoire of group II introns, providing a framework for future investigation of genome plasticity in phytoplasmas.
Rodents are substantial reservoirs of zoonotic viruses with regular human exposure restricted to a limited number of species. Numerous rodent species have been shown to harbor emerging viruses, including paramyxoviruses and hepaciviruses. Reed voles (Alexandromys fortis), a rodent species that inhabits grasslands and riparian environments throughout East Asia, remain poorly characterized in terms of their viral diversity. In this study, 258 A. fortis specimens collected from rural areas in Gyeonggi Province, Republic of Korea (ROK) were screened for paramyxoviruses and subjected to metagenomic next-generation sequencing. Genome characterization, phylogenetic and cophylogenetic assessments, and prediction of signal peptidase cleavage sites were performed to analyze the molecular features of the identified viruses. Zoonotic potential was evaluated using a genome-based machine-learning model. A nearly complete genome of a novel paramyxovirus, designated as Pyeongtaek Alexandromys paramyxovirus (PyAPV), was identified in six A. fortis specimens, with all sequences clustering within the genus Jeilongvirus. A nearly complete genome of a rodent-associated hepacivirus was also obtained from four specimens and classified as a distinct lineage within the species Hepacivirus J. These findings demonstrate the role of A. fortis as a natural reservoir of emerging viruses and expand current knowledge of rodent-associated viral diversity in the ROK.
Lymphocystis disease viruses (LCDVs), members of the Lymphocystivirus genus of the Iridoviridae family, infect various freshwater and marine fish species. They cause the chronic disease lymphocystis, which is non-fatal, but substantially reduces the commercial value of the infected fish. To date, four genotypes of LCDV (LCDV1-4) have been identified, all of which encode the viral homologue of B-cell lymphoma 2 (Bcl-2), a key inhibitor of apoptosis. In this study, we performed biochemical and structural analyses of LCDV2 Bcl-2. Binding assays revealed that LCDV2 Bcl-2 exhibits binding selectivity toward BH3 domain-containing zebrafish proteins. It interacted with zBaxA and zNoxa, but not with zBaxB, zBid, or zBeclin 1, distinguishing it from mammalian and herpesviral Bcl-2 proteins. Subsequent structural determination of LCDV2 Bcl-2 in complex with the BH3 domain of zBaxA demonstrated that they interact in a canonical manner, primarily mediated by the BH3 consensus motif residues of zBaxA. In addition, a subpocket formed by two phenylalanine residues in LCDV2 Bcl-2 plays a key role in determining binding selectivity.
Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000-489 000), 144 000 deaths (131 000-162 000), and 11·7 million (10·7-13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5-36·1) globally, from 197 000 (173 000-218 000) in 1990, but increased in the WHO African region by 55·6% (25·5-92·4), from 31 500 (24 900-38 500) to 49 000 (42 600-58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5-26·5) in GBD 2017 to 10·5% (8·1-13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2-52·0) of global childhood cancer deaths in 2023. Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.
As modern populations spend the majority of their time indoors, understanding indoor microbial ecology is crucial for public health. While research has addressed abiotic pollutants, the ecological dynamics of surface-associated mycobiomes remain insufficiently understood. This study assessed fungal communities across 25 types of public facilities in South Korea to evaluate the relative influence of environmental parameters and human-driven factors. A total of 327 surface samples from six surface types (handles, tables, chairs, walls, pillars, floors) were analyzed using internal transcribed spacer (ITS) sequencing, yielding 27 million reads and 31,721 amplicon sequence variants (ASVs). Although temperature and humidity significantly correlated with airborne fungal concentration, they exerted minimal influence on community diversity and structure. Instead, the intensity of human contact with indoor surfaces emerged as a primary driver of fungal community composition. We found that the relative abundance of the human-associated genus Malassezia is strongly associated with two distinct ecological states of indoor surface mycobiomes; high-Malassezia samples exhibited significantly distinct communities (ANOSIM R = 0.217, p < 0.001) and dense co-occurrence networks among genera of potential clinical relevance, with strong correlations between Malassezia and both Aspergillus and Cladosporium (|corr| = 0.81). These Malassezia-associated patterns persisting across diverse facilities demonstrate that human-driven microbes are the primary ecological drivers of surface mycobiomes in public spaces, providing foundational evidence for human contact-based microbial assessments in public health monitoring and hygiene-conscious environment design.
Marine dinoflagellates are gaining attention as sustainable bioresource for polyunsaturated fatty acids (PUFAs), particularly omega-3 such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present study, we analyzed the FAs and transcriptomic profiles of marine dinoflagellates Amphidinium carterae (D-044) and Prorocentrum minimum (D-127) to evaluate their potential as FAs producers. Gas chromatography-FA methyl ester (GC-FAME) analysis showed that A. carterae is a superior omega-3 producer, yielding a total FA content of 67.6 mg/g DW. DHA accounted for 26.7% of the total FAME profile, which is significantly higher than that of P. minimum (18.1 mg/g DW; DHA 13.1%). Gene Ontology (GO) annotation revealed genes related to FAs and lipid metabolism in A. carterae (1,217 genes) and in P. minimum (2,317 genes), which provide a molecular basis for dinoflagellates with high lipid productivity. Notably, three lipid droplet-associated hydrolase (LDAH) genes with diverse evolutionary origins were identified from A. carterae. These findings suggest a potential expansion of the genetic repertoire related to lipid storage and metabolism, highlighting A. carterae and LDAH as candidates for future biotechnological applications and microalgal metabolic engineering.
Carbapenem-resistant Enterobacterales (CRE) poses a significant public health threat. In Korea, the current surveillance systems do not distinguish between colonisation and infection. This study evaluated the clinical and socioeconomic burden of CRE infections in Korea. This retrospective study was conducted at 15 medical institutions. All patients with CRE-positive clinical specimens in 2022 were classified as either 'CRE-infected' or 'colonised'. Clinical data and medical costs were collected for the 'CRE-infected' cohort. A predictive logistic regression model based on sex, age, presence of bacteraemia, and bacterial species was developed to estimate the nationwide incidence of CRE infections. For cases of CRE bacteraemia, the clinical information of the matched control groups (no-infection, 3rd-generation-cephalosporin [3GC]-susceptible infection, and 3GC-resistant infection) was collected. Among the 4848 reported CRE cases, 1087 (22.4%) were classified as infections, including 586 bacteraemia cases. The most common infection sites were intra-abdominal (34.0%) and pulmonary (31.3%). Carbapenemase-producing Enterobacterales accounted for 74.2% of cases, with Klebsiella pneumoniae carbapenemase (84.4%) being the most prevalent. The 30-day and 90-day mortality rates were 29.3% and 40.8%, respectively. The predictive model estimated 7117 CRE infections nationwide, including 1897 cases of bacteraemia. The economic burden of CRE infections in 2022 was estimated to be $517,738,296, with excess costs ranging from $108,382,302 to $401,186,712, compared with carbapenem-susceptible infections and cases without infection. This study highlights the substantial clinical and socioeconomic burden of CRE infections in Korea. Given the continued increase in reported CRE cases even after 2022, urgent measures are required to address this growing public health challenge.
BACKGROUND: Hypogeous fungi play important ecological roles and have significant economic value. However, the hypogeous habit of these organisms hinders our understanding of their diversity and vulnerability. RESULTS: The first comprehensive assessment of the hypogeous fungal diversity in Korea was conducted using environmental DNA metabarcoding, encompassing 643 soil samples collected from 162 nationwide grids. A total of 186 phylotypes of hypogeous fungi (representing 32 genera) were identified through phylogeny-based identification using a curated ITS reference database that comprised 3,359 sequences from 693 species (83 genera). This number largely exceeds the 30 species recorded in Korea. The environmental preference analysis revealed two distinct ecological clusters of hypogeous fungal genera, respectively vulnerable to climate warming and to soil eutrophication. Based on geographic range criteria (Area of Occupancy and Extent of Occurrence), 10 of 15 phylotypes exhibited distribution patterns consistent with Endangered or Vulnerable thresholds. CONCLUSIONS: These findings reveal extensive cryptic diversity, establish baseline conservation data for hypogeous fungi, and provide a replicable methodology for global hypogeous fungal assessments in soil ecosystems.
Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. GBD is a systematic, scientific effort aimed at quantifying the comparative magnitude of health loss caused by diseases, injuries, and risk factors across age groups, sexes, and geographical locations over time. We estimated meningitis mortality using the Cause of Death Ensemble model (CODEm) and morbidity using DisMod-MR 2.1, incorporating data from vital registration, verbal autopsy, surveillance, hospital data, and systematic reviews. Aetiology-specific estimates were generated with pathogen-linked case-fatality ratios and splined binomial regression models. Risk factor attribution was based on established risk-outcome pairs and population attributable fractions. In 2023, there were 259 000 (95% uncertainty interval 202 000-335 000) global deaths and 2·54 million (2·20-2·93) incident cases of meningitis. Children younger than 5 years accounted for more than a third of deaths (86 600 [53 300-149 000]). Streptococcus pneumoniae, Neisseria meningitidis, non-polio enteroviruses, and other viruses were the leading causes of death, while non-polio enteroviruses caused the most cases. The four WHO-defined preventable meningitis pathogens of interest (S pneumoniae, N meningitidis, Haemophilus influenzae, and Group B streptococcus) contributed to 98 700 deaths (77 000-127 000) and 594 000 cases (514 000-686 000). Low birthweight, short gestation, and household air pollution were the top risk factors for meningitis-related mortality. Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings. Gates Foundation, Wellcome Trust, and UK Department of Health and Social Care.
This study presents the first investigation of acetyl-11-keto-β-boswellic acid (AKBA)'s anti-human cytomegalovirus (HCMV) activity in vitro and elucidates its underlying mechanisms. In HCMV Towne strain-infected WI-38 cells, AKBA (1-12 μM) exhibited negligible cytotoxicity while significantly suppressing virus-induced cytopathic effects (CPE) at 6-10 μM, with dose-dependent reduction of viral proteins (IE1/2 and p52) expression, viral DNA copy number (UL123, UL44, and UL32), and infectious viral progeny titer (TCID50). Time-of-addition experiments demonstrated the primary antiviral activity of AKBA during post-entry phase, along with direct virion inactivation. Transcriptome analysis revealed that AKBA significantly downregulated the expression of the host factor NR4A1 induced by HCMV, a finding further validated by Western blotting. Further gene knockdown experiments confirmed that silencing NR4A1 significantly reduced the expression of viral proteins IE1/2, thereby validating NR4A1 as a key host factor for HCMV infection. These findings indicate that AKBA has a potent and dose-dependent inhibitory effect on HCMV replication in WI-38 cells, and proves that this effect is mediated through two different mechanisms: one is the downregulation of the expression of the key host factor NR4A1, and the other is the direct inactivation of HCMV viral particles.
Two novel bacterial strains, designated as YS3T and YS5T, were isolated from soil collected at Nogo Mountain, Gyeonggi-do, Republic of Korea. Strain YS3T is Gram-positive, aerobic, non-motile and rod-shaped, forming opaque, cream-coloured colonies with smooth surfaces. Phylogenetic analysis based on the 16S rRNA gene sequence revealed the highest similarity to Pseudarthrobacter humi RMG13T (99.2%) and Pseudarthrobacter siccitolerans 4J27T (99.2%). Strain YS3T grew at 4-35 °C (optimum, 30 °C), at pH 4.0-12.0 (optimum, pH 8.0), and tolerated up to 6% (w/v) NaCl, with optimal growth occurring in the absence of NaCl. The genomic G+C content of strain YS3T was 65.0 mol%. Average nucleotide identity (ANI) values between strain YS3T and related Pseudarthrobacter species ranged from 81.2% to 84.9%, while digital DNA-DNA hybridization (dDDH) values ranged from 20.7% to 39.0%. Strain YS5T is Gram-negative, aerobic, motile and rod-shaped, forming translucent, yellow colonies with smooth surfaces. Phylogenetic analysis based on the 16S rRNA gene sequence showed the highest similarity to Ideonella dechloratans CCUG 30898T (98.9%) and Ideonella alba 3Y2T (98.7%). Strain YS5T grew at 10-35 °C (optimum, 30 °C), at pH 4.0-12.0 (optimum, pH 8.0), and tolerated up to 1% (w/v) NaCl, with optimal growth in the absence of NaCl. The genomic G+C content of strain YS5T was 69.0 mol%. ANI values between strain YS5T and Ideonella species ranged from 77.9% to 81.2%, while dDDH values ranged from 15.1% to 22.4%. On the basis of phenotypic, genotypic, phylogenetic and chemotaxonomic evidence, strain YS3T represents a novel species of the genus Pseudarthrobacter, for which the name Pseudarthrobacter cremeus sp. nov. is proposed (type strain YS3T=KACC 24143T=TBRC 21184T). Similarly, strain YS5T represents a novel species of the genus Ideonella, for which the name Ideonella flava sp. nov. is proposed (type strain YS5T=KACC 24144T=TBRC 21186T).
Antibiotic resistance genes (ARGs) are increasingly recognized as global determinants within the 'One Health' framework; however, the diversity of ARGs and their transmission mechanisms across the ocean-atmosphere interface remain poorly understood. In this study, we simultaneously quantified airborne and seawater-derived ARGs along a 3868 km transect covering Korean coastal waters, the North Pacific Ocean, and the Bering Sea. The normalized relative abundance of ARGs (copies/16S rRNA gene) varied across 10 targeted ARG subtypes, with average values of 1.1 × 10-4 ± 5.5 × 10-4 copies/16S rRNA gene in aerosol and 1.7 × 10-4 ± 1.1 × 10-3 copies/16S rRNA gene in seawater. The blaTEM and tetBP genes were dominant subtypes in both matrices, reflecting their roles as core components of the marine resistome. Furthermore, specific genes, including tetA, tetZ, ermB, qnrD, and oqxA, showed proportional enrichment in aerosols, indicating matrix-specific distribution patterns. Exploratory partial canonical correspondence analysis (pCCA) revealed that air mass origin (oceanic vs. terrestrial) and meteorological variables (e.g., air temperature, solar radiation, wind speed, and atmospheric pressure) significantly influence the spatial distribution of airborne ARGs. In addition, Polaribacter sp. and Sediminibacterium sp. were identified as putative microbial hosts potentially facilitating the mobilization of airborne ARGs across the ocean. Strong correlations between intI1 and certain ARGs (e.g., oqxA, ermB, and blaTEM) further suggest the potential role of horizontal gene transfer in resistance dissemination. Our findings provide a critical baseline indicating that airborne ARGs are widely disseminated in remote marine environments, emphasizing the need for global monitoring of the atmospheric resistome.
Postbiotics derived from lactic acid bacteria (LAB) have attracted growing interest as stable and potentially safer alternatives to probiotics for use in foods and health-related products. Comprehensive safety evaluation remains essential before their broader application. In this study, we assessed the safety profiles of RHT3201, a postbiotic preparation derived from Lacticaseibacillus rhamnosus IDCC 3201, through genomic, genotoxic, acute oral, and subchronic oral toxicity studies. Whole-genome analysis showed that IDCC 3201 lacks antimicrobial resistance genes and exhibits no hemolytic activity, supporting the genomic safety of the source strain. RHT3201 showed no genotoxic potential in either in vitro or in vivo assays, as evidenced by no structural or numerical chromosomal aberrations at concentrations up to 5,000 μg/ml in CHL/IU cells and no increase in micronucleated polychromatic erythrocytes, with no suppression of bone marrow erythropoiesis by oral administration of RHT3201 at doses up to 15,000 mg/kg/day using a mouse model. In rats, single oral doses of up to 15,000 mg/kg caused no mortality, treatment-related clinical signs, or gross pathological abnormalities, indicating an approximate lethal dose greater than 15,000 mg/kg. In a 90-day repeated-dose oral toxicity study, no adverse treatment-related effects were observed at doses up to 5,000 mg/kg/day. Mild liver and thyroid histopathological findings were considered adaptive and reversible. Accordingly, the no-observed-adverse-effect level was determined to be 5,000 mg/kg/day. Taken together, these findings support the safety of RHT3201 as a LAB-derived postbiotic ingredient.