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Institution

Mahidol University

EducationBangkok, Nakhon Pathom, Thailand
About: Mahidol University is a education organization based out in Bangkok, Nakhon Pathom, Thailand. It is known for research contribution in the topics: Population & Malaria. The organization has 23758 authors who have published 39761 publications receiving 878781 citations.


Papers
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Journal ArticleDOI
TL;DR: Molecular docking suggested that the cytotoxicity of reported hybrids could be possibly due to their dual inhibition of α- and β-tubulins at GTP and colchicine binding sites, respectively, and falcipain-2 was identified to be a plausible target site of the hybrids given their antimalarial potency.

162 citations

Journal ArticleDOI
TL;DR: In this article, pembro significantly improved PFS and OS over chemo as first-line therapy for metastatic NSCLC without targetable alterations and PD-L1 TPS ≥ 50%.
Abstract: LBA4Background: In KEYNOTE-024, pembro significantly improved PFS (primary end point) and OS (secondary end-point) over chemo as first-line therapy for metastatic NSCLC without targetable alterations and PD-L1 TPS ≥50%. In KEYNOTE-042, we compared pembro with chemo at the lower TPS of ≥1% (NCT02220894). Methods: Eligible patients (pts) were randomized 1:1 to ≤35 cycles of pembro 200 mg Q3W or investigator’s choice of ≤6 cycles of paclitaxel + carboplatin or pemetrexed (peme) + carboplatin with optional peme maintenance (nonsquamous only). Randomization was stratified by region (east Asia vs non-east Asia), ECOG PS (0 vs 1), histology (squamous vs nonsquamous), and TPS (≥50% vs 1-49%). Primary end-points were OS in pts with TPS ≥50%, ≥20%, and ≥1%. OS differences were assessed sequentially using the stratified log-rank test. Efficacy boundaries at the prespecified second interim analysis were one-sided P = .0122, .01198, and .01238, respectively. Results: 1274 pts were randomized: 637 to each arm. 599 pts ...

162 citations

Journal ArticleDOI
TL;DR: In a murine model, there was a striking difference in virulence between Ara- and Ara+ B. pseudomallei, which suggests that the biotype is stable.
Abstract: Two distinct types of Burkholderia pseudomallei, differentiated by the ability to assimilate L-arabinose but with similar morphologies and antigenicities, can be isolated from soil in Thailand. Approximately 25% of soil isolates from northeast Thailand were arabinose assimilators (Ara+), but in 1,200 sequentially studied patients, only arabinose "nonassimilators" (Ara-) caused melioidosis (P < 0.0001). In a murine model, there was a striking difference in virulence between Ara- and Ara+ B. pseudomallei. The mean (standard deviation) 50% lethal dose (LD[50]) inoculum for Ara- isolates was 182 (111) CFU/mouse compared with approximately 10(9) CFU/mouse for Ara+ soil isolates. There was no significant difference between the LD(50)s for clinical and soil Ara- isolates. All attempts to convert the biochemical phenotype by selective culture failed, which suggests that the biotype is stable.

162 citations

Journal ArticleDOI
TL;DR: Evidence is provided that FcgammaR polymorphisms may be an important predisposing factor also in Thais in a complex manner.
Abstract: We recently reported association of a newly identified polymorphism of Fcgamma receptor (FcgammaR) IIb, I232T, with systemic lupus erythematosus (SLE) in Japanese. To date, information on FcgammaR genotypes and their association with SLE is limited in South-east Asian populations. To gain further insight into the role of FcgammaR polymorphisms in the genetic predisposition of SLE, association of FcgammaRIIa-H131R, IIb-I232T, IIIa-F176V and IIIb-NA1/NA2 (HNA-1a/1b) polymorphisms with SLE was analyzed in the Thai population, using case-control association analysis. FcgammaRIIb-232T/T and IIIb-NA2/NA2 genotypes were associated with SLE with the odds ratio of 2.55. Genotype relative risk analysis revealed significant association of IIb-232T/T and IIIb-NA2/NA2, and a tendency of association of the IIIa-176F/F genotype. Moreover, carriers of FcgammaRIIa-131R were significantly increased in patients with lupus nephritis. Significant linkage disequilibrium was present among FcgammaRIIb, IIIa and IIIb, and two-locus analyses suggested that the tendency of association of FcgammaRIIIa could derive from linkage disequilibrium with IIb and IIIb. These results provided evidence that FcgammaR polymorphisms may be an important predisposing factor also in Thais in a complex manner.

162 citations

Journal ArticleDOI
TL;DR: The model-derived assessment suggests that the efficacy of artesunate on ring stage parasites is reduced significantly in Pailin, which supports the hypothesis that artemisinin resistance mainly reflects reduced ring-stage susceptibility and predicts that doubling the frequency of dosing will accelerate clearance of art Artemisinin-resistant parasites.
Abstract: Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia. Resistance is characterized by prolonged in vivo parasite clearance times (PCTs) following artesunate treatment. The biological basis is unclear. The hypothesis that delayed parasite clearance results from a stage-specific reduction in artemisinin sensitivity of the circulating young asexual parasite ring stages was examined. A mathematical model was developed, describing the intrahost parasite stage-specific pharmacokinetic–pharmacodynamic relationships. Model parameters were estimated using detailed pharmacokinetic and parasite clearance data from 39 patients with uncomplicated falciparum malaria treated with artesunate from Pailin (western Cambodia) where artemisinin resistance was evident and 40 patients from Wang Pha (northwestern Thailand) where efficacy was preserved. The mathematical model reproduced the observed parasite clearance for each patient with an accurate goodness of fit (rmsd: 0.03–0.67 in log10 scale). The parameter sets that provided the best fits with the observed in vivo data consist of a highly conserved concentration–effect relationship for the trophozoite and schizont parasite stages, but a variable relationship for the ring stages. The model-derived assessment suggests that the efficacy of artesunate on ring stage parasites is reduced significantly in Pailin. This result supports the hypothesis that artemisinin resistance mainly reflects reduced ring-stage susceptibility and predicts that doubling the frequency of dosing will accelerate clearance of artemisinin-resistant parasites.

162 citations


Authors

Showing all 23819 results

NameH-indexPapersCitations
Nicholas J. White1611352104539
Pete Smith1562464138819
Randal J. Kaufman14049179527
Kevin Marsh12856755356
Barry M. Trost124163579501
John R. Perfect11957352325
Jon Clardy11698356617
François Nosten11477750823
Paul Turner114109961390
Paul Kubes10939341022
Ian M. Adcock10766042380
Peter H. Verburg10746434254
Guozhong Cao10469441625
Carol L. Shields102142446800
Nicholas P. J. Day10270850588
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202329
2022187
20213,386
20203,028
20192,630
20182,531