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98 result(s) for "Melissa Teo"
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Surfactant-guided spatial assembly of nano-architectures for molecular profiling of extracellular vesicles
The controlled assembly of nanomaterials into desired architectures presents many opportunities; however, current preparations lack spatial precision and versatility in developing complex nano-architectures. Inspired by the amphiphilic nature of surfactants, we develop a facile approach to guide nanomaterial integration – spatial organization and distribution – in metal-organic frameworks (MOFs). Named surfactant tunable spatial architecture (STAR), the technology leverages the varied interactions of surfactants with nanoparticles and MOF constituents, respectively, to direct nanoparticle arrangement while molding the growing framework. By surfactant matching, the approach achieves not only tunable and precise integration of diverse nanomaterials in different MOF structures, but also fast and aqueous synthesis, in solution and on solid substrates. Employing the approach, we develop a dual-probe STAR that comprises peripheral working probes and central reference probes to achieve differential responsiveness to biomarkers. When applied for the direct profiling of clinical ascites, STAR reveals glycosylation signatures of extracellular vesicles and differentiates cancer patient prognosis. Current methods for controlled assembly of nanomaterials into desired architectures often lack the precision and versatility to develop complex architectures. Here the authors report STAR, surfactant tunable spatial architecture, to guide nanomaterial integration in metal-organic frameworks.
A hydrogel-based mechanical metamaterial for the interferometric profiling of extracellular vesicles in patient samples
The utility of mechanical metamaterials for biomedical applications has seldom been explored. Here we show that a metamaterial that is mechanically responsive to antibody-mediated biorecognition can serve as an optical interferometric mask to molecularly profile extracellular vesicles in ascites fluid from patients with cancer. The metamaterial consists of a hydrogel responsive to temperature and redox activity functionalized with antibodies to surface biomarkers on extracellular vesicles, and is patterned into micrometric squares on a gold-coated glass substrate. Through plasmonic heating, the metamaterial is maintained in a transition state between a relaxed form and a buckled state. Binding of extracellular vesicles from the patient samples to the antibodies on the hydrogel causes it to undergo crosslinking, induced by free radicals generated via the activity of horseradish peroxidase conjugated to the antibodies. Hydrogel crosslinking causes the metamaterial to undergo fast chiral re-organization, inducing amplified changes in its mechanical deformation and diffraction patterns, which are detectable by a smartphone camera. The mechanical metamaterial may find broad utility in the sensitive optical immunodetection of biomolecules. A hydrogel-based metamaterial undergoing shape and optical changes amplified in response to antibody-mediated biorecognition can be used to molecularly profile extracellular vesicles in ascites fluid from patients with cancer.
An Optimised Protocol Harnessing Laser Capture Microdissection for Transcriptomic Analysis on Matched Primary and Metastatic Colorectal Tumours
Generation of large amounts of genomic data is now feasible and cost-effective with improvements in next generation sequencing (NGS) technology. Ribonucleic acid sequencing (RNA-Seq) is becoming the preferred method for comprehensively characterising global transcriptome activity. Unique to cytoreductive surgery (CRS), multiple spatially discrete tumour specimens could be systematically harvested for genomic analysis. To facilitate such downstream analyses, laser capture microdissection (LCM) could be utilized to obtain pure cell populations. The aim of this protocol study was to develop a methodology to obtain high-quality expression data from matched primary tumours and metastases by utilizing LCM to isolate pure cellular populations. We demonstrate an optimized LCM protocol which reproducibly delivered intact RNA used for RNA sequencing and quantitative polymerase chain reaction (qPCR). After pathologic annotation of normal epithelial, tumour and stromal components, LCM coupled with cDNA library generation provided for successful RNA sequencing. To illustrate our framework’s potential to identify targets that would otherwise be missed with conventional bulk tumour sequencing, we performed qPCR and immunohistochemical technical validation to show that the genes identified were truly expressed only in certain sub-components. This study suggests that the combination of matched tissue specimens with tissue microdissection and NGS provides a viable platform to unmask hidden biomarkers and provides insight into tumour biology at a higher resolution.
Laparoscopic wedge resection for suspected large (≥5 cm) gastric gastrointestinal stromal tumors
Background Laparoscopic wedge resection (LWR) for small gastric gastrointestinal stromal tumors (GIST) is now widely accepted, but its application for large GISTs remains controversial. This study aims to evaluate the feasibility and safety of LWR for suspected large (≥5 cm) gastric GISTs. Methods Retrospective review of 82 consecutive patients who underwent attempted LWR for suspected gastric GIST. LWR for large (≥5 cm) ( n  = 23) tumors was compared with LWR for small (<5 cm) tumors ( n  = 59). The 23 patients with LWR for large tumors were also compared to 36 consecutive patients who underwent open wedge resection (OWR) for large tumors. Results Comparison between patients who underwent LWR for large versus small tumors demonstrated that resection of large tumors was associated with a longer operating time. There was no difference in other perioperative outcomes, and oncological outcomes such as frequency of close margins (≤1 mm) and recurrence-free survival. Comparison between patients who underwent LWR versus OWR for large tumors showed that LWR was associated with decreased median time to fluid or solid diet, shorter postoperative stay but longer operating times. There was no difference in oncological outcomes. Conclusion LWR for suspected large gastric GIST is feasible and safe. It is associated with similar short-term outcomes with LWR for small tumors and favorable short-term outcomes over OWR for large tumors without compromising on oncological outcomes.
Validation of the MSKCC Gastrointestinal Stromal Tumor Nomogram and Comparison with Other Prognostication Systems: Single-Institution Experience with 289 Patients
Purpose To validate the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic nomogram in a single-institution cohort of patients with gastrointestinal stromal tumors (GISTs), and to compare its predictive accuracy against other established risk classification systems, including the National Institutes of Health (NIH), Armed Forces Institute of Pathology (AFIP), and Joensuu criteria. Methods We retrospectively reviewed 289 patients who underwent surgical resection for primary localized GISTs without adjuvant imatinib therapy and compared the actuarial recurrence-free survival (RFS) with the predicted RFS. Results Tumors >5 cm in size, with high mitotic index, and which had ruptured were significantly associated with recurrent disease. The 2-year RFS was 77.2 % [95 % confidence interval (CI) 71.6–81.8], and the 5-year RFS was 67.9 % (95 % CI 61.7–73.4). The concordance probability of the nomogram of 2-year RFS was 0.71 (SE 0.02), and 5-year RFS was 0.71 (SE 0.19). The 2-year and 5-year MSKCC nomogram probability calculations and the AFIP criteria gave a better estimation of RFS compared to the NIH ( p  < 0.001) and Joensuu ( p  < 0.001) criteria. There was no significant difference between the predictive accuracy of the nomogram compared to the AFIP criteria. Conclusions The MSKCC nomogram slightly underestimated the probability of RFS after surgical resection of GISTs. It was associated with a significantly better predictive accuracy compared to the NIH and Joensuu. This study suggests that there is a wider than expected prognostic divergence between gastric GISTs versus GISTs arising from the small intestine.
Repeat Cytoreductive Surgery and HIPEC for Peritoneal Surface Malignancy and Peritoneal Carcinomatosis
Background Peritoneal-based malignancy (PBM), especially peritoneal carcinomatosis from gastrointestinal malignancies traditionally carries a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) have been shown to attain long median survival of 34–92 months and 5 year survival of 29–59 % in patients with favorable histopathological subtypes. Recurrence after CRS and HIPEC poses a management dilemma. This paper evaluates our institution’s experience with repeat CRS and HIPEC, its associated morbidity and outcomes. Methods One-hundred and thirty underwent CRS and HIPEC for PBM from April 2001 to June 2013. 49 had peritoneal recurrences, of which 24 had peritoneal only recurrence. 7 out of the 24 underwent a second CRS and HIPEC. Results Five females and two males with median age of 51 (37–63), underwent a second CRS and HIPEC. The primary malignancies were: 1 peritoneal mesothelioma, 3 appendiceal, 2 ovarian, and 1 colorectal cancers. Median peritoneal cancer indices for the initial and second CRS were 19 and 12, respectively. Completeness of cytoreduction score of 0 was achieved for all patients. Median hospitalization after second CRS and HIPEC was 12 days (7–60). 1 out of 7 (14 %) experienced grade 3 or 4 post-operative complications. There was no 30-day or inpatient mortality. Median follow-up was 13 months (1–97). Median disease-free interval between the first CRS and HIPEC to peritoneal recurrence was 20 months (14–87). Median disease-free survival of 6 months (1–97) was achieved after the second CRS and HIPEC. Six patients remained alive without disease and one passed away with disease. Two had recurrences at 12 and 71 months after second CRS and HIPEC, 1 died and the other, still alive, went on to have a third CRS. Conclusion Repeat CRS and HIPEC can achieve prolonged survival in selected patients with peritoneal-based malignancies, and can be performed with acceptable morbidity and mortality.
Prospective Quality of Life Study for Colorectal Cancer Patients with Peritoneal Carcinomatosis Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is becoming accepted treatment for peritoneal carcinomatosis (PC) from colorectal cancer. Quality of life (QoL) for patients after surgery is still a concern amongst physicians despite studies that show that QoL recovers after surgery. We conducted a prospective QoL study on patients undergoing CRS and HIPEC and attempt to identify factors that affect the QoL. Methods Patients who underwent CRS and HIPEC for PC from colorectal cancer from March 2012 to January 2015 were included. The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and the colorectal module (QLQ-CR29) were administered prior to surgery and thereafter at 3, 6, and 12 months. Results Twenty-three patients underwent 25 procedures. Median disease-free survival was 12.9 months [95 % confidence interval (CI) 2.5–19.3]. Physical and role functioning scores decreased at 3 months but returned to baseline at 6 months. There were significant increases in emotional and social functioning scores at 6–12 months and improvements in all symptoms scales at 6–12 months, especially the fatigue and appetite scores. A higher PCI score, longer duration of surgery, the presence of a stoma, and recurrence within 3 months were associated with a poorer QoL. Conclusions QoL after CRS and HIPEC improved or returned to baseline in all categories by 6–12 months after surgery. Patient selection is important not only for improved survival but also for improved QoL.
A machine learning approach to identify predictive molecular markers for cisplatin chemosensitivity following surgical resection in ovarian cancer
Ovarian cancer is associated with poor prognosis. Platinum resistance contributes significantly to the high rate of tumour recurrence. We aimed to identify a set of molecular markers for predicting platinum sensitivity. A signature predicting cisplatin sensitivity was generated using the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas databases. Four potential biomarkers (CYTH3, GALNT3, S100A14, and ERI1) were identified and optimized for immunohistochemistry (IHC). Validation was performed on a cohort of patients (n = 50) treated with surgical resection followed by adjuvant carboplatin. Predictive models were established to predict chemosensitivity. The four biomarkers were also assessed for their ability to prognosticate overall survival in three ovarian cancer microarray expression datasets from The Gene Expression Omnibus. The extreme gradient boosting (XGBoost) algorithm was selected for the final model to validate the accuracy in an independent validation dataset (n = 10). CYTH3 and S100A14 , followed by nodal stage, were the features with the greatest importance. The four gene signature had comparable prognostication as clinical information for two-year survival. Assessment of tumour biology by means of gene expression can serve as an adjunct for prediction of chemosensitivity and prognostication. Potentially, the assessment of molecular markers alongside clinical information offers a chance to further optimise therapeutic decision making.
Mapping Two Decades of AI in Construction Research: A Scientometric Analysis from the Sustainability and Construction Phases Lenses
The construction industry plays a vital role in the urbanization process and global economy, and there is a growing interest in utilizing artificial intelligence (AI) technologies to improve sustainability, productivity, and efficiency. However, there is a lack of comprehensive analysis regarding the progression of AI in the construction context, particularly from the sustainability angle. This study aims to fill this gap by conducting a scientometric analysis of AI research in construction by focusing on historical clusters, emerging trends, research clusters, and the correlation between sustainability pillars and key project stages. A Scopus search, between January 2000 and July 2023, was conducted that used 25 construction industry-related keywords, resulting in a total of 9564 publications. After evaluating practical AI applications in construction, 3710 publications were selected for further analysis using VOSviewer for visual diagrams and to further understand connections and patterns between literature. The findings revealed that: (a) Literature on AI in construction has experienced steady growth over the past two decades; (b) Machine learning, deep learning, and big data are seen as the key enabling digital technologies in the construction sector’s performance; (c) Economic and governance pillars of sustainability exhibit the highest potential for AI adoption; (d) Design and construction phases demonstrate substantial advantages for AI adoption; (e) AI technologies have become, despite adoption challenges, a strong driver of construction industry modernization, and; (f) By incorporating AI, the construction industry can advance towards a more sustainable future by consolidating its processes and practices.
Preoperative platelet-lymphocyte ratio is an independent prognostic marker and superior to carcinoembryonic antigen in colorectal peritoneal carcinomatosis patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Objective The aim of this study was to examine the prognostic significance of preoperative inflammatory-based indices, platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and carcinoembryonic antigen (CEA) in predicting overall survival (OS) in patients with colorectal peritoneal carcinomatosis (CPC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods Sixty patients with pathologically confirmed CPC treated with CRS and HIPEC between 2003 and 2015 were included. Levels of preoperative PLR, NLR, and CEA were recorded. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Results Median OS was 36 months (95% CI, 26.6-45.4) and 5-year OS was 40.5% (95% CI, 27.3-51.6%). Preoperative PLR (p = 0.034) and CEA (p = 0.036) were found to be significant prognostic markers of OS, whereas NLR did not affect OS. PLR remained significant on multivariate analysis (hazard ratio, 1.035; 95% CI, 1.027-1.043; p < 0.001). Conclusion Our study indicates that preoperative PLR may be used as a prognostic marker in CPC patients undergoing CRS and HIPEC and could be useful in the preoperative setting when selecting patients for surgery. The subset of patients with PLR > 300 have a median OS of 5 months (95% CI, 0-24.6 months), indicating that CRS and HIPEC may not be superior to systemic chemotherapy in this subset of patients.