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Recent Submissions
Uncovering resistance pathways to first- and last-line antibiotics in Mycobacterium tuberculosis populations
(2026-05-01) Srilohasin P.; Williams J.M.; Tay A.P.; Gillieatt B.F.; Pascoe D.R.; Maharjan R.P.; Chaipraset A.; Ajawatanawong P.; Cain A.K.; Srilohasin P.; Mahidol University
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the world's deadliest diseases, currently responsible for ~1.5 million deaths per year and rising. Recently, rifampicin-resistant M. tuberculosis was designated as a critical priority pathogen status by the World Health Organization. However, few controlled laboratory studies are available that systematically assess the molecular drivers of antibiotic resistance development in TB. In this study, we paired laboratory-directed evolution and population-level deep-sequencing approaches to map the evolutionary pathways taken by M. tuberculosis to develop resistance to first- and last-line therapies (rifampicin and linezolid) and then characterized de novo resistance mutation occurrence over time. We demonstrated that the majority of M. tuberculosis populations readily acquire mutations in genes commonly found in rifampicin- and linezolid-resistant clinical isolates (rpoB and rplC). However, we also identified mutations in six genes, mostly present in subpopulations (17-41%) and not previously linked to rifampicin or linezolid resistance, including four associated with rifampicin resistance (Rv0052, ppsD, ppsE and mptC) and two associated with linezolid resistance (glpK and echA12). The ppsD, glpK and mptC mutations were also identified in published individual sequencing reads of antibiotic-resistant clinical isolates. Further investigation of the identified resistance determinants ppsD/E established that mutations in these genes appear to mediate resistance across multiple species, with an Escherichia coli mutant of the ortholog (fabF), representing a shared domain featured in PpsD and PpsE, phenotypically displaying increased antibiotic tolerance to low-level rifampicin. This study highlights the power of using controlled laboratory studies to uncover minority variants in populations of M. tuberculosis. These outcomes will lead to improved diagnosis of antibiotic resistance emergence in TB, to optimize management and treatment of TB infections, and ultimately to minimize patient deaths.
Mortality risk due to non-optimum temperatures by cause of death, age, and sex: a multi-country time-series study
(2026-05-01) Wen B.; Wu Y.; Xu R.; Yu P.; Liu Y.; Yu W.; Ye T.; Huang W.; Yang Z.; Zhang Y.; Xu Z.; Zhou S.; Zhang Y.; Ju K.; Hales S.; Lavigne E.; Saldiva P.H.N.; de Sousa Zanotti Stagliorio Coelho M.; Matus P.; Seposo X.T.; Kim H.; Guo Y.L.; Tantrakarnapa K.; Kliengchuay W.; Capon A.; Bi P.; Jalaludin B.; Hu W.; Green D.; Zhang Y.; Phung D.; Guo Y.; Li S.; Wen B.; Mahidol University
Background: Non-optimum temperatures have been linked to increased mortality, but the cause-, age-, and sex-specific impacts remain largely unclear. This study investigates the temperature–mortality relationships for nine causes of death across multiple countries/territories and explores subgroup differences by sex and age. Methods: We analysed the non-linear and lagged associations between temperature and mortality in 1117 locations from ten countries or territories (Australia, Brazil, Canada, Chile, Mexico, New Zealand, Philippines, South Korea, Taiwan, and Thailand) covering country-specific periods within 2000–2019, using a two-stage time-series design. In the first stage, a quasi-Poisson generalised linear regression with a distributed lag non-linear model was fitted to estimate the location-specific mortality risk associated with temperature. We then applied a meta-regression model in the second stage to synthesise the associations for cause-specific mortality. Stratified analyses were conducted by sex and age group, and the attributable fraction (AF) of mortality was subsequently estimated. Findings: We identified three distinct exposure-response patterns: an inverse J-shaped curve with higher risks from extreme cold for most causes, a U-shaped curve for all-cause and respiratory mortality, and a J-shaped curve for injury and external causes with greater risks at extreme heat. Significant differences in temperature-related mortality risks were observed across age and sex groups, with the direction and magnitude of these differences varying by cause of death. We estimated that 2.03 million deaths were attributable to non-optimum temperatures during the study period, corresponding to 4.38% (95% CI: 2.02, 6.59) of all-cause mortality. The highest AFs were observed for mental disorders (6.53%), nervous (6.40%), and cardiovascular causes (5.71%). For most causes of death, cold temperatures accounted for the largest proportion of mortality. However, for deaths related to infectious as well as injury and external causes, heat exposure contributed to the majority of the mortality. Interpretation: Our findings demonstrated substantial variations in temperature-related mortality by cause of death, sex, and age. This analysis highlights the need for tailored public health strategies that address the unique vulnerabilities of specific demographic groups across different causes of death, with targeted interventions to mitigate temperature-related health risks. Future work should focus on improving estimation in data-sparse subgroups and developing cause-, age-, and sex-specific projections of temperature-related health risks under future climate scenarios. Funding: The Australian Research Council, Australian National Health and Medical Research Council, VicHealth, and National Research Council of Thailand.
Genomic characterization of clinical Stenotrophomonas strains from Thailand reveals five putative novel genospecies and extensive functional diversity
(2026-12-01) Thant E.P.; Klaysubun C.; Palittapongarnpim P.; Singkhamanan K.; Yingkajorn M.; Yaikhan T.; Chaichana N.; Pomwised R.; Wonglapsuwan M.; Chusri S.; Chukamnerd A.; Tongsima S.; Phornsiricharoenphant W.; Phokhaphan P.; Sunthornthummas S.; Sudtachat N.; Ngamphiw C.; Surachat K.; Thant E.P.; Mahidol University
Stenotrophomonas spp. are increasingly recognized as opportunistic pathogens with high levels of antimicrobial resistance (AMR). Despite their clinical importance, genomic diversity within the genus remains underexplored, particularly in Thailand and Southeast Asia. Ten Stenotrophomonas strains were isolated from diverse clinical specimens at Songklanagarind Hospital, Thailand, in 2023. Whole genome sequencing was performed using MGISEQ 2000 platform. Genome-based classification was assessed via average nucleotide identity (ANI), and digital DNA-DNA hybridization (dDDH). Functional annotation was conducted using RAST and COG databases. Pan-genome structure, AMR/virulence genes, and phenotypic traits (biofilm and hemolysis) were investigated. The genomes ranged from 4.11 to 5.05 Mb with 66.02–66.84% GC content. While 16S rRNA gene sequences showed high similarity to type strains, ANI and dDDH analyses clearly differentiated the ten studied strains from validly published species and grouped them into five putative novel genospecies. The pan-genome was open, with only 21.6% core, 1.5% soft-core and 76.9% accessory/unique genes, indicating high plasticity. Functional annotation revealed enrichment in genes related to regulation, metabolism, and cell envelope biogenesis, reflecting metabolic flexibility and environmental adaptability. AMR profiling showed conserved aminoglycoside-modifying enzymes, β-lactamase blaL1 and efflux pumps across all strains. Phenotypically, all strains exhibited multidrug resistance but remained uniformly susceptible to cotrimoxazole, the current treatment of choice. Virulence genes for adhesion, hemolysin, proteases, and biofilm were conserved, consistent with observed α-hemolysis and moderate-to-strong biofilm formation. This study reveals substantial genomic and functional diversity among ten Stenotrophomonas strains, highlighting five putative novel genospecies and underscoring the importance of continued surveillance and accurate identification for effective clinical management strategies.
Effects of massive transfusion (10-20 litres) versus ultramassive transfusion (≥20 litres) on mortality in adult liver transplant recipients: A propensity-score matched study
(2026-05-01) Tran Z.; Raykateeraroj N.; Suh J.; Ismail J.; Fink M.; Caragata R.; Perini M.V.; Koshy A.N.; Lee D.K.; Weinberg L.; Tran Z.; Mahidol University
Background Ultramassive perioperative fluid transfusion during orthotopic liver transplantation (OLT) identifies a high-risk recipient phenotype and is associated with substantially increased mortality compared with conventional massive transfusion. OLT frequently necessitates high-volume fluid resuscitation, yet the prognostic implications of ultramassive perioperative transfusion in this setting remain uncertain. We evaluated whether ultramassive transfusion (≥20 L total perioperative fluid) is independently associated with worse survival than massive transfusion (10– < 20 L) in adult OLT recipients. Methods In this single-centre retrospective cohort (2009–2023), we included adults undergoing primary OLT who received ≥10 L of total perioperative fluid (crystalloids, colloids, blood, and blood products administered intraoperatively and within 24 hours postoperatively). Propensity score matching was used to compare recipients receiving ultramassive (≥20 L) versus massive (10– < 20 L) transfusion, balancing recipient, donor, and intraoperative characteristics. Primary outcomes were 90-day, 3-year, and overall all-cause mortality; secondary outcomes included graft failure, graft and patient survival time, primary non-function, early allograft dysfunction, thrombotic complications, acute kidney injury, and hospital length of stay. Results Of 993 OLT recipients, 306 (30.8%) received ≥10 L perioperative fluid and comprised the unmatched cohort. In the propensity-matched cohort (n = 188), ultramassive transfusion was associated with significantly higher 90-day, 3-year and overall mortality compared with massive transfusion, with consistent effect estimates across multiple matching strategies and sensitivity analyses. In contrast, ultramassive transfusion showed no robust or consistent association with early allograft dysfunction, thrombotic complications, graft loss, or other secondary endpoints, likely reflecting low event rates and limited power. Conclusions Among adult OLT recipients exposed to high-volume perioperative resuscitation, ultramassive transfusion delineates a distinct high-risk phenotype characterised by substantially increased short- and long-term mortality. Although causal inference is precluded by the observational design, these findings suggest that reaching an ultramassive transfusion threshold may mark a particularly vulnerable subgroup that warrants intensified intraoperative optimisation strategies and tailored long-term surveillance.
Role of pH on hetero-aggregation of modified natural rubber and silica particles in latex medium and its physical and mechanical properties
(2026-10-05) Abdulraman D.; Sunintaboon P.; Amornsakchai T.; Phinyocheep P.; Abdulraman D.; Mahidol University
To achieve effective reinforcement of silica in natural rubber (NR) composites, it is essential to enhance the interaction between NR and silica particles to improve mechanical performance. In this study, NR latex was chemically modified to a low-degree epoxidation (5 mol%), designed as ENR-5. The average particle size (d₅₀) of ENR-5 latex increased to 6.1 µm—approximately ten times larger than that of unmodified NR—due to reduced surface charge and subsequent aggregation of rubber particles following epoxidation. The pH of ENR-5 latex, equal to 3, was further adjusted to 7, 10, and 12 using NaOH, resulting in progressive decrease of particle size to 3.4, 2.0, and 1.3 µm, respectively. A latex-based mixing of NR with 40 phr silica, named NR-40Si composite, exhibited homo-aggregation of NR-NR and silica-silica particles due to poor compatibility between the non-polar NR and polar silica surfaces. While ENR-5-pH3–40Si demonstrated pronounced hetero-aggregation between rubber and silica, driven by favorable interactions between epoxide and silanol groups. Increasing the pH of ENR-5 latex resulted in decreasing the hetero-aggregation sizes. Morphological analysis of the dried ENR-5-silica composites indicated that the dispersion of silica in the rubber matrix was closely related to the hetero-aggregation behavior in the latex phase. ENR-5-pH3 particles promoted the successful formation of hetero-aggregates of the rubber with silica, strengthening the rubber–silica interactions and enhancing thermal and mechanical properties better than other composites. This latex-stage mixing approach represents a simple, effective, and environmentally friendly (green) strategy for significantly improving the performance of silica-reinforced rubber composites.