Mahidol University's Institutional Repository
คลังสารสนเทศสถาบันของมหาวิทยาลัยมหิดล
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Recent Submissions
Intranasal Administration of Bivalent RBD Nanoparticles Elicits Strong Systemic Responses That Effectively Block Distal Dissemination of COVID-19
(2025-01-01) Seesen M.; Sunintaboon P.; Limthongkul J.; Janhirun Y.; Lerdsamran H.; Wiriyarat W.; Ubol S.; Jearanaiwitayakul T.; Seesen M.; Mahidol University
The intranasal vaccine against coronavirus disease 2019 (COVID-19) has gained more attention because of its ability to induce both mucosal and systemic immune responses. We have recently developed a c-GAMP-adjuvanted bivalent receptor-binding domain (RBD) vaccine, derived from the ancestral strain and the Omicron variant. We demonstrated here that intranasal administration of this vaccine candidate triggers not only the respiratory but also the systemic immune response against SARS-CoV-2. The immunized mice elicited the broadly neutralizing antibodies against the ancestral strain (Wuhan-1) and variants of concern (Delta, Omicron BA.1, and Omicron BA.5). This route of vaccination also induced potent systemic T cell responses with strong cytotoxic activity against both the Wuhan-1 and Omicron BA.1 strains. Additionally, intranasally immunized mice significantly suppressed SARS-CoV-2 RNA levels in circulation and spleens, indicating effective containment of the virus beyond the respiratory tract. These findings suggest that the intranasal bivalent RBD vaccine holds promise for combating SARS-CoV-2 infections.
Structurally Oriented Classification of FOXA1 Alterations Identifies Prostate Cancers with Opposing Clinical Outcomes and Distinct Molecular and Immunologic Subtypes
(2025-03-03) Hwang J.; Likasitwatanakul P.; Deshmukh S.K.; Wu S.; Kwon J.J.; Toye E.; Moline D.; Evans M.G.; Elliott A.; Passow R.; Luo C.; John E.; Gandhi N.; McKay R.R.; Heath E.I.; Nabhan C.; Reizine N.; Orme J.J.; Domingo Domenech J.M.; Sartor O.; Baca S.C.; Dehm S.M.; Antonarakis E.S.; Hwang J.; Mahidol University
PURPOSE: Around 10% to 15% of prostate cancers harbor recurrent aberrations in the Forkhead Box A1 gene, FOXA1, whereby the alteration type and the effect on the forkhead (FKH) domain affect protein function. We developed a FOXA1 classification system to inform clinical management. EXPERIMENTAL DESIGN: A total of 5,014 prostate cancer samples were examined using whole-exome and -transcriptome sequencing from the Caris Life Sciences database. We denoted class 1 FOXA1 alterations as missense and in-frame insertions/deletions with subclasses oriented with respect to the FKH domain. These were in the first part of the FKH domain [class 1A: amino acids (AA) 168-246], within the Wing2 region of FKH (class 1B: AA 247-269), or outside FKH (class 1C: AA 1-167, 270+). Two hotspot missense mutations at R219 were denoted class 2. Class 3 included predicted truncating mutations with subclasses partitioned based on the FKH domain (class 3A: AA 1-269 and class 3B: AA 270+). Class 4 represented FOXA1 amplifications. Real-world overall survival and therapy outcomes were determined from insurance claims. RESULTS: FOXA1 alterations did not influence survival when considered in aggregate but had distinct prognostic effects when stratified by class. In primary prostate samples, class 1A alterations were associated with overall improved survival (HR, 0.57; P = 0.03); a similar trend was seen in metastatic biopsies with class 1B (HR, 0.84; P = 0.09). Conversely, in primary specimens, class 1C exhibited worse survival upon second-generation androgen receptor signaling inhibitor treatment (HR, 1.93; P < 0.001). Class 2 mutations (R219C/S) were enriched in neuroendocrine prostate cancers and were associated with overall poor survival (HR, 2.05; P < 0.001) and worse outcomes to first-line androgen-deprivation therapies (HR, 2.5; P < 0.001). Class 3A alterations indicated improved survival (HR, 0.70; P = 0.01), whereas class 3B alterations portended poor outcomes (HR, 1.50; P < 0.001). Amplifications (class 4) indicated poor outcomes in metastatic samples (HR, 1.48; P = 0.02). Molecularly, different FOXA1 alteration classes harbored distinct mutational and immunologic features as well as unique transcriptional programs. Finally, relative to European Americans, African Americans had increased class 1C alterations, whereas Asian/Pacific Islander patients had increased class 1B alterations. CONCLUSIONS: FOXA1 alterations should not be interpreted in aggregate, as different classes are associated with divergent molecular features and clinical outcomes. Our revised classification schema facilitates clinical decision-making for patients with prostate cancer and uncovers important racial differences.
Platelet Responses to Urethane Dimethacrylate-Based Bone Cements Containing Monocalcium Phosphate/ϵ-Polylysine: Role of ϵ-Polylysine in In Vitro Wound Healing Induced by Platelet-Derived Growth Factor-BB
(2025-03-12) Klaihmon P.; Sungkhaphan P.; Thavornyutikarn B.; Kitpakornsanti S.; Septham P.; Young A.; Lorthongpanich C.; Janvikul W.; Singhatanadgit W.; Klaihmon P.; Mahidol University
Platelets play a pivotal role in initiating bone fracture healing. However, the interaction between platelets and bone cements used for fracture repair remains relatively unexplored. This study investigated the platelet response to recently developed urethane dimethacrylate-based bone cements containing 8% (w/w) monocalcium phosphate monohydrate (MCPM) and/or 5% (w/w) ϵ-polylysine (PLS). All experimental bone cements achieved final monomer conversions of 75-78%, compared with the 86% conversion of the commercial PMMA bone cement Kyphon. The MCPM and PLS microparticles, varying in size, were dispersed within the glass-filler-incorporated polymer matrix. In contrast to Kyphon, all experimental cements exhibited significantly smoother and more hydrophilic surfaces. Bone cements incorporating PLS, with or without MCPM, effectively activated platelets by inducing cellular adhesion, aggregation, and extracellular-signal-regulated kinase (ERK) activation, comparable to Kyphon. Flow cytometry analysis demonstrated a statistically significant increase in CD62P-positive platelets following exposure to PLS-incorporated bone cements and exogenously administered PLS in a concentration-dependent manner, but not with Kyphon. A wound healing assay revealed a 2-fold enhancement in wound closure within 24 h and exceeding 85% at 48 h by bone cements containing PLS, with or without MCPM, and Kyphon. Notably, platelet-derived growth factor BB (PDGF-BB) secretion was significantly elevated, specifically after platelet exposure to PLS-incorporated bone cements, a phenomenon not observed with Kyphon. Interestingly, PDGF-BB neutralization attenuated wound closure induced by the PLS-incorporated bone cements. In conclusion, the urethane dimethacrylate-based bone cements containing PLS demonstrated a significant enhancement in platelet activation and PDGF-BB secretion, which, at least partly, enhanced in vitro wound closure. The results suggest that PDGF-BB plays a crucial role in the PLS-mediated enhancement of wound healing in these bone cements.
Optimizing Stroke Recognition with MediaPipe and Machine Learning: An Explainable AI Approach for Facial Landmark Analysis
(2025-01-01) Ul Karim R.; Mahdi S.; Samin A.; Zereen A.N.; Abdullah-Al-Wadud M.; Uddin J.; Ul Karim R.; Mahidol University
Early detection of stroke is critical for improving survival rates and recovery. This study presents an innovative approach to stroke diagnosis through the analysis of facial landmarks combining MediaPipe's facial landmark detection with advanced machine learning models - Random Forest (RF), Extreme Gradient Boosting (XGB), and Categorical Boosting (CB). A comprehensive dataset of stroke and non-stroke facial images are curated, with MediaPipe extracting 228 facial landmarks from key regions affected by stroke-related asymmetry. Explainable AI (XAI) techniques are applied to enhance model interpretability, allowing for a deeper understanding of the most significant facial regions contributing to stroke prediction. The machine learning models are individually optimized through hyperparameter tuning, and further we propose a Multimodal Voting Classifier (MVC). By aggregating the predictions through majority voting or weighted averaging, the system reduces the likelihood of incorrect classifications that might arise from a single model's limitations. This results in a more stable and generalized model with improved diagnostic accuracy, as demonstrated by its 94.75% accuracy, than any individual model's performance. Feature importance analysis, facilitated by XAI, identified key facial regions - such as the eyes, cheeks, and lips - as critical indicators of stroke, significantly improving the model's diagnostic precision. Additionally, t-SNE visualization is employed to provide insight into classifying the stroke and non-stroke cases, reinforcing the model's robustness. Real-time metrics show the model's efficiency and adaptability across diverse hardware, enabling practical clinical integration. The proposed system offers a cost-effective, non-invasive diagnostic tool that can be implemented in real-time, potentially improving accessibility to stroke diagnosis in remote and resource-limited areas.
Dynamics of ammonia-oxidizing microorganisms in gradient temperature-regulated reactors under low ammonia loading condition
(2025-04-01) Sonthiphand P.; Songkriengkrai N.; Charanaipayuk N.; Termsaithong T.; Suwannasilp B.B.; Mhuantong W.; Limpiyakorn T.; Sonthiphand P.; Mahidol University
Ammonia-oxidizing microorganisms (AOMs) play a crucial role in nitrogen removal in engineered systems. However, temperature fluctuations can lead to ammonia oxidation failure. This study investigated the effects of a broad temperature range (10.5, 14, 17.5, 21, 26.4, 35, 38.5, 42, and 45.5 °C) on the distribution of ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and comammox together with Nitrospira and Nitrobacter in gradient temperature-regulated reactors operated under low ammonia loading condition. Quantitative PCR and high throughput sequencing revealed that the AOA amoA gene numbers (∼104 copies/ng DNA) were relatively high at 38.5 °C to 42 °C, suggesting AOA favoring higher temperature than lower temperature. The amoA genes of AOA (∼103 - 104 copies/ng DNA) outcompeted those of AOB (∼103 copies/ng DNA) and comammox (