Authors: Tan, Wei Phin | Tan, Wei Shen | Inman, Brant A.
Article Type: Systematic Review
Abstract: Background: Immune checkpoint inhibitors (ICI) are extremely expensive and most patients with metastatic urothelial carcinoma (mUC) do not benefit significantly from their use. Objective: We performed a systematic review and meta-analysis to determine response rates and survival outcomes on patients with mUC progressing despite prior platinum-based chemotherapy receiving ICI stratified by biomarker status. Methods: We performed a comprehensive literature search for all articles in PubMed and Embase up to 06/15/2019 to identify all studies pertaining to programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) receptor targeted therapies for mUC that reported biomarkers. Given that biomarkers are reported on different …scales and with different metrics, we defined each biomarker as either positive or negative using the definitions implemented in each individual trial. We meta-analyzed the data, reconstructed overall (OS) and progression-free survival (PFS) curves, and analyzed response rates by biomarker status. OS and PFS were analyzed in a pooled Kaplan-Meier analysis and pseudo-individualized patient data (IPD) extracted. Results: We identified 1429 manuscripts of which 8 met inclusion criteria, with a total of 1837 treated patients with outcomes data. On proportional hazards survival analysis, patients in the biomarker negative group were associated with a lower PFS (HR 1.48, 95% CI: 1.18 - 1.85, p < 0.001) and lower OS (HR 1.54, 95% CI: 1.32 - 1.80, p < 0.001) when compared to the biomarker positive group. Response data was available for 1641 patients and random effects proportion show complete response in 8% and 3% in biomarker positive and negative patients, respectively. Conclusions: ICI therapy for metastatic UC post platinum therapy has a higher overall response rate, OS and PFS in patients who are biomarker positive compared to those who are negative. However, some patients who are biomarker negative do achieve complete responses. A better biomarker for patient selection is essential before biomarkers can be used to stratify candidates for ICI therapy. Show more
Keywords: PD-L1, PD-1, B7-H1, B7H1 biomarker, systematic review, meta-analysis
DOI: 10.3233/BLC-190238
Citation: Bladder Cancer, vol. 5, no. 3, pp. 211-223, 2019
Authors: Tan, Wei Ying | Hargreaves, Carol | Chen, Christopher | Hilal, Saima
Article Type: Research Article
Abstract: Background: The major mechanisms of dementia and cognitive impairment are vascular and neurodegenerative processes. Early diagnosis of cognitive impairment can facilitate timely interventions to mitigate progression. Objective: This study aims to develop a reliable machine learning (ML) model using socio-demographics, vascular risk factors, and structural neuroimaging markers for early diagnosis of cognitive impairment in a multi-ethnic Asian population. Methods: The study consisted of 911 participants from the Epidemiology of Dementia in Singapore study (aged 60– 88 years, 49.6% male). Three ML classifiers, logistic regression, support vector machine, and gradient boosting machine, were developed. Prediction results of independent classifiers were combined …in a final ensemble model. Model performances were evaluated on test data using F1 score and area under the receiver operating curve (AUC) methods. Post modelling, SHapely Additive exPlanation (SHAP) was applied on the prediction results to identify the predictors that contribute most to the cognitive impairment prediction. Findings: The final ensemble model achieved a F1 score and AUC of 0.87 and 0.80 respectively. Accuracy (0.83), sensitivity (0.86), specificity (0.74) and predictive values (positive 0.88 negative 0.72) of the ensemble model were higher compared to the independent classifiers. Age, ethnicity, highest education attainment and neuroimaging markers were identified as important predictors of cognitive impairment. Conclusion: This study demonstrates the feasibility of using ML tools to integrate multiple domains of data for reliable diagnosis of early cognitive impairment. The ML model uses easy-to-obtain variables and is scalable for screening individuals with a high risk of developing dementia in a population-based setting. Show more
Keywords: Cognitive impairment, machine learning, socio-demographic, structural MRI, vascular risk factors
DOI: 10.3233/JAD-220776
Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 449-461, 2023
Authors: Yang, Liuzhu | Yan, Xinping | Xu, Zunying | Tan, Wei | Chen, Zhong | Wu, Bo
Article Type: Research Article
Abstract: Purpose: A previous study showed that a 1-h delay in treatment of thoracic spinal cord injury (SCI) with recombinant human erythropoietin (rhEPO) lacked neuroprotective efficacy. The aim of the present study was to reassess delayed administration of different doses of rhEPO on acute spinal cord compressive injury in rats. Methods: The experiment was divided into first and second stages, which SCI rats were observed for 4 and 28 days, respectively. All rats were randomly divided into four groups at both stages: control group, and rhEPO-3,000U (Unit), rhEPO-4,000U and rhEPO-5,000U groups. SCI rats received rhEPO treatment at different time points. The …primary indicators were locomotor recovery, histopathology, apoptotic index, inflammatory index, ultrastructural scoring system and volume of areas of demyelination. Results: The most significant locomotor functional and histopathological improvements and the best myelin protection were observed after administration of 5,000 U/kg rhEPO. rhEPO at 3,000, 4,000 and 5,000 U/kg showed similar ultrastructural neuroprotection, as well as similar inhibition of apoptosis and regulation of inflammation. Conclusion: Delayed administration of rhEPO can reduce apoptosis and inflammation, and promote myelin repair and functional recovery following spinal cord compressive injury in rats. Show more
Keywords: Erythropoietin, delayed treatment, spinal cord injury, myelin, functional recovery, rats
DOI: 10.3233/RNN-150498
Citation: Restorative Neurology and Neuroscience, vol. 34, no. 4, pp. 647-663, 2016
Authors: Mo, Tong | Zhang, Rong | Li, Weiping | Zhang, Jingbo | Wu, Zhonghai | Tan, Wei
Article Type: Research Article
Abstract: To improve the efficiency of elderly assessments, an influence-based fast preceding questionnaire model (FPQM) is proposed. Compared with traditional assessments, the FPQM optimizes questionnaires by reordering their attributes. The values of low-ranking attributes can be predicted by the values of the high-ranking attributes. Therefore, the number of attributes can be reduced without redesigning the questionnaires. A new function for calculating the influence of the attributes is proposed based on probability theory. Reordering and reducing algorithms are given based on the attributes’ influences. The model is verified through a practical application. The practice in an elderly-care company shows that the FPQM …can reduce the number of attributes by 90.56% with a prediction accuracy of 98.39%. Compared with other methods, such as the Expert Knowledge, Rough Set and C4.5 methods, the FPQM achieves the best performance. In addition, the FPQM can also be applied to other questionnaires. Show more
Keywords: Questionnaire, reorder, reduce, fast preceding questionnaire model, elderly assessment
DOI: 10.3233/IDA-163320
Citation: Intelligent Data Analysis, vol. 22, no. 2, pp. 407-437, 2018
Authors: Tan, Wei-Qiang | Yuan, Li | Cao, Xu | Wu, Xiao-Yuan | Xing, Yi-Qun | Ye, Ming
Article Type: Research Article
Abstract: BACKGROUND: Long non-coding RNA (LncRNA) TUG1 plays a critical role in the development of human cancers. This study explored whether TUG1 is involved in the cytotoxicity of dendritic cells and cytokine-induced killer cells (DCs-CIK), an immunotherapy approach, in neuroblastoma. METHODS: A TUG1 expression plasmid was transfected into DCs. Neuroblastoma SK-N-SH cells were incubated with CIK cells, DCs-CIK cells, and TUG1-overexpressing DCs-CIK cells, with or without irradiation. SK-N-SH cell viability, colony formation, migration, and apoptosis were analyzed using CCK-8, colony formation assay, transwell assay, and flow cytometry, respectively. Production of IL-12, IL-2 and IFN-γ in the supernatants was determined using ELISA. …A dual luciferase activity assay was performed to confirm the molecular interactions between TUG1 and miR-204. Tumor-bearing mice were established by injection of SK-N-SH cells followed by stimulation with CIK cells, DC-CIK cells, and TUG1-overexpressing DCs-CIK cells. RESULTS: Compared to CIK alone or DC-CIK therapy, overexpression of TUG1 significantly suppressed tumor cell proliferation, colony formation, and migration of neuroblastoma cells. Moreover, upregulation of TUG1 robustly induced apoptosis and altered key molecules associated with apoptosis and epithelial-mesenchymal transition. Contents of IL-12, IL-2 and IFN-γ were dramatically elevated in the supernatants in the coculturing system upon transfection with TUG1. In addition, TUG1 was found to be act as miR-204 sponge. Furthermore, in vivo experiments demonstrated that upregulation of TUG1 potentiated the antitumor activity of DC-CIK immunotherapy. CONCLUSION: Overexpression of TUG1 promotes DC maturation and enhances CIK cytotoxicity, suggesting that TUG1 may be a novel target for enhancing DC-CIK based immunotherapy for neuroblastoma. Show more
Keywords: Neuroblastoma, immunotherapy, lncRNA TUG1
DOI: 10.3233/CBM-210436
Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 53-61, 2023
Authors: Grimberg, Dominic C. | Shah, Ankeet | Tan, Wei Phin | Etienne, Wiguins | Spasojevic, Ivan | Inman, Brant A.
Article Type: Research Article
Abstract: BACKGROUND: Nearly 70% of all new cases of bladder cancer are non-muscle invasive disease, the treatment for which includes transurethral resection followed by intravesical therapy. Unfortunately, recurrence rates approach 50% in part due to poor intravesical drug delivery. Hyperthermia is frequently used as an adjunct to intravesical chemotherapy to improve drug delivery and response to treatment. OBJECTIVE: To assess the solubility profile of intravesical chemotherapies under varying conditions of pH and temperature. METHODS: Using microplate laser nephelometry we measured the solubility of three intravesical chemotherapy agents (mitomycin C, gemcitabine, and cisplatin) at varying physical conditions. Drugs were assessed at room …temperature (23°C), body temperature (37°C), and 43°C, the temperature used for hyperthermic intravesical treatments. To account for variations in urine pH, solubility was also investigated at pH 4.00, 6.00, and 8.00. RESULTS: Heat incrementally increased the solubility of all three drugs studied. Conversely, pH largely did not impact solubility aside for gemcitabine which showed slightly reduced solubility at pH 8.00 versus 6.00 or 4.00. Mitomycin C at the commonly used 2.0 mg/mL was insoluble at room temperature, but soluble at both 37 and 43°C. CONCLUSIONS: Hyperthermia as an adjunct to intravesical treatment would improve drug solubility, and likely drug delivery as some current regimens are insoluble without heat. Improvements in solubility also allow for testing of alternative administration regimens to improve drug delivery or tolerability. Further studies are needed to confirm that improvements in solubility result in increased drug delivery. Show more
Keywords: Bladder cancer, intravesical chemotherapy, solubility, hyperthermia, nephelometry
DOI: 10.3233/BLC-200350
Citation: Bladder Cancer, vol. 6, no. 4, pp. 461-470, 2020
Authors: Tan, Wei-Qiang | Yuan, Li | Wu, Xiao-Yan | He, Cheng-Guang | Zhu, Shai-Cheng | Ye, Ming
Article Type: Research Article
Abstract: Accumulating evidence validates that aerobic glycolysis is involved in chemotherapy resistance in human malignant tumors. In the present study, we explored the role of exosome-delivered circular RNA DLGAP4 (circDLGAP4), a novel identified circRNAs, in the chemoresistance of neuroblastoma (NB) cells. Our study demonstrated that doxorubicin-resistant cells expressed higher HK2, accompanied with enhanced glycolysis. In addition, circDLGAP4 was validated to act as a sponge for the HK2-targeting miR-143. As a molecular cargo, exosomes were found to deliver circDLGAP4 from doxorubicin-resistant cells to the sensitive cells. Functionally, exosomal circDLGAP4 enhanced glycolysis and drug resistance via regulating miR-143 and HK2 in NB cells. …Consistently, upregulation of HK2 induced by circDLGAP4 or miR-143 inhibitors produced the similar malignant transformation in NB cells. However, knockdown of circDLGA P4 could reversed the drug resistance in the recipient cells. In conclusion, these findings demonstrate that exosome-delivered circDLGAP4 promotes the glycolysis, proliferation, and invasion of sensitive NB cells by regulating miR-143 and HK2, providing a novel link between drug resistance and circDLGAP4/miR-143/HK2 axis in drug-resistant NB. Show more
Keywords: Neuroblastoma, exosomes, CircDLGAP4, glycolysis, drug resistance
DOI: 10.3233/CBM-210272
Citation: Cancer Biomarkers, vol. 34, no. 3, pp. 375-384, 2022
Authors: Tan, Natalie Woon Hui | Pan, Woei-Jack | Yunos, Hernie Haryati Binte Mohd | Tan, Wei Chuen | Lim, Kevin Boon-Leong
Article Type: Research Article
Abstract: Pyogenic abscess formation is a known but rare complication following childhood immunization. We present a retrospective review of seven infants in Singapore with methicillin-sensitive Staphylococcus aureus abscesses following a 5-in-1 vaccine (diphtheria toxoid-tetanus toxoid-acellular pertussis, inactivated Poliomyelitis and Haemophilus influenzae type b) administration in the thigh that required surgical drainage. The children were 4 to 7 months old at the time of diagnosis. All of them presented with thigh swelling and fever was manifested in six infants. Four patients had ultrasound examination prior to surgery. A breach of sterility during immunization at one center most likely accounted for a cluster …of four cases. Health care personnel should have a high index of suspicion for post-vaccination abscess especially in a child that presents with limb swelling, with or without fever, and with a history of recent vaccination in the same limb. An ultrasound examination to diagnose intramuscular abscess is recommended for equivocal cases. Prevention strategies include strict adherence to sterility during immunization and timely reporting of post-vaccination abscesses to health care authorities. Show more
Keywords: Vaccination, abscess, surgical drainage
DOI: 10.3233/JPI-2010-0239
Citation: Journal of Pediatric Infectious Diseases, vol. 5, no. 2, pp. 139-147, 2010
Authors: Kee, Su Keyau | Hsu-Lin See, Valene | Chia, Patrick | Tan, Wei Ching | Tien, Sim Leng | Lim, Soon Tiong Alvin
Article Type: Research Article
Abstract: The t(11;22) rearrangement is the most common recurrent familial reciprocal translocation in man. Heterozygote carriers are phenotypically normal but are at risk of subfertility in the male, miscarriages, and producing chromosomally unbalanced offspring. The unbalanced progeny usually results from an extra der(22) chromosome resulting from a 3:1 malsegregation. We present here a family with t(11;22). Of six siblings, three were found to be carriers following prenatal diagnosis of the proband fetus. Neither of the two married carrier siblings have a live born child. In keeping with the prevailing knowledge of the pregnancy outcomes of heterozygote carriers, between the siblings they …had recurrent miscarriages, a fetus with a +der(22) chromosome, and other subfertility issues resulting in multiple failed in vitro fertilization cycles with preimplantation genetic diagnosis. However, unlike the siblings, their extended family comprising their heterozygote translocation mother, married aunts and an uncle had normal fertility and a lack of a history of miscarriages or an abnormal child. The differing outcomes may be related to the male partners having additional semen anomalies which may further exacerbate problems associated with the t(11;22). Because the t(11;22) rearrangement tends to run in families, it is recommended that chromosome studies are offered to family members of an affected relative as an option, and provide them with appropriate genetic counseling so that they will have the necessary information with regard to their risk for subfertility, miscarriages, and production of viable unbalanced offspring. Follow-up prenatal diagnosis should also be offered to affected expectant family members, especially after preimplantation genetic diagnosis. Show more
Keywords: Emanuel syndrome, subfertility, miscarriage, preimplantation genetic diagnosis, +der(22)t(11;22) syndrome
DOI: 10.3233/PGE-13046
Citation: Journal of Pediatric Genetics, vol. 2, no. 1, pp. 37-42, 2013
Authors: Yu, Wei-Ye | Zhang, Qian Qian | Xiao, Yong | Tan, Wei-Guo | Li, Xiang-Dong | Lu, Pu-Xuan
Article Type: Research Article
Abstract: OBJECTIVE: To explore the difference of 18F-FDG PET/CT images between the symptomatic and asymptomatic pulmonary tuberculosis, as well as the correlation between the standard uptake value (SUV) and the symptomatic/asymptomatic pulmonary tuberculosis. METHODS: A study dataset of 57 pulmonary tuberculosis cases was retrospectively assembled and analyzed. Among these cases, 30 were diagnosed having symptomatic pulmonary tuberculosis and 27 were asymptomatic pulmonary tuberculosis. PET/CT was performed in all 57 cases. The clinical data, CT images and PET/CT radioactive uptake data were analyzed using statistical data analysis software. RESULTS: All 57 cases showed radioactively high uptake, with the maximum standard uptake value …(SUVmax) of the lesion ranging from 1.60 to 27.30 and a mean value of 6.63±4.82. The symptomatic cases had an SUVmax of 8.76±4.97 and the asymptomatic cases had an SUVmax of 4.27±3.39. The SUVmax as well as singular or multiple lesions showed statistical differences between symptomatic and asymptomatic cases. CONCLUSION: The symptomatic pulmonary tuberculosis cases show significantly higher SUVmax than the asymptomatic cases. Based on the criteria of SUVmax greater than 2.0 to define active lesions, 100% of symptomatic cases might have active lesions while 70.4% of asymptomatic cases might have active lesions. Therefore, focused attention should be clinically paid on the asymptomatic cases of pulmonary tuberculosis to avoid miss diagnosis and delayed treatment. Show more
Keywords: PET/CT, active, pulmonary tuberculosis
DOI: 10.3233/XST-190543
Citation: Journal of X-Ray Science and Technology, vol. 27, no. 5, pp. 899-906, 2019
