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"Ang, Andrea"
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Chinatown unbound : trans-Asian urbanism in the age of China
Chinatowns' are familiar places in almost all major cities in the world. In popular Western wisdom, the restaurants, pagodas, and red lanterns are intrinsically equated with a self-contained, immigrant Chinese district, an alien enclave of 'the East' in 'the West'. By the 1980s, when these Western societies had largely given up their racially discriminatory immigration policies and opened up to Asian immigration, the dominant conception of Chinatown was no longer that of an abject ethnic ghetto: rather, Chinatown was now seen as a positive expression of multicultural heritage and difference. By the early 21st century, however, these spatial and cultural constructions of Chinatown as an 'other' space - whether negative or positive - have been thoroughly destabilised by the impacts of accelerating globalisation and transnational migration. This book provides a timely and much-needed paradigm shift in this regard, through an in-depth case study of Sydney's Chinatown. It speaks to the growing multilateral connections that link Australia and Asia (and especially China) together; not just economically, but also socially and culturally, as a consequence of increasing transnational flows of people, money, ideas and things. Further, the book elicits a particular sense of a placein Sydney's Chinatown: that of an inte-connected world in which Western and Asian realms inhabit each other, and in which the orientalist legacy is being reconfigured in new deployments and more complex delimitations.. As such, Chinatown Unbound engages with, and contributes to making sense of, the epochal shift in the global balance of power towards Asia, especially China.
Book
A Comprehensive Review of the Role of Rho-Kinase Inhibitors in Corneal Diseases
There is growing interest in the application of Rho-associated protein kinase (ROCK) inhibitors (ROCKI) to the treatment of corneal diseases. ROCK is a key regulator of several cellular processes in the cornea, including cytoskeletal organization, cell proliferation, migration, inflammation, and wound healing. ROCKI, such as ripasudil and netarsudil, enhances endothelial cell migration, and promotes repair in conditions characterized by endothelial dysfunction. These agents also exert anti-inflammatory, anti-angiogenic, and anti-fibrotic effects for wound healing. As such, ROCKI demonstrate promise as therapeutic options for conditions such as Fuchs’ endothelial corneal dystrophy, pseudophakic bullous keratopathy, and iridocorneal endothelial syndrome. Emerging data further supports ROCKI’s potential in managing corneal neovascularization and supporting recovery following cataract surgery and keratoplasty, reducing the need for donor tissue. This narrative review provides a comprehensive evaluation of ROCKI’s mechanism of action, pharmacological properties, safety profile, applications in corneal disease management, emerging clinical trials, and novel approaches. We emphasize both preclinical and clinical findings, highlight existing evidence gaps, and outline future research priorities.
Journal Article
Metabolic syndrome and its effect on the outcomes of rheumatoid arthritis in a multi-ethnic cohort in Singapore
Introduction
Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes.
Aim
We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes.
Method
Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions. Univariable and multivariable regression modelling were used to investigate the associations between patients’ demographics with MetS and MetS with RA outcomes.
Results
The prevalence of MetS in our RA cohort was 49.4% and 44.9% according to the JC and NCEP ATP III definitions, respectively. The diagnosis of MetS was largely due to hypertriglyceridemia, hypertension, and obesity. MetS was associated with older age (OR 1.06 [95% CI 1.04–1.08]), Malay ethnicity (OR 1.78 [95% CI 1.02–3.09]), or Indian ethnicity (OR 3.07 [95% CI 1.68–5.59]). No significant associations between MetS and RA outcomes were observed. RA patients with MetS are more likely to suffer from stroke and ischemic heart disease.
Conclusion
The prevalence of MetS in RA patients in Singapore was almost double that in the general population. MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. RA patients, especially those older and of Indian and Malay ethnicities, should be routinely screened for MetS. Any MetS-defining condition should be actively controlled.
Key Points
• Approximately half of the RA sample from the Singapore RA population can be diagnosed with MetS.
• Older patients, and patients of Malay and Indian ethnicities have higher odds of MetS.
• MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease.
Journal Article
Keratoconus International Consortium (KIC)- advancing keratoconus research
Clinical relevance
The Keratoconus International Consortium (KIC) will allow better understanding of keratoconus.
Background
Keratoconus is a disorder characterised by corneal elevation and thinning, leading to reduced vision. The current gaps in understanding of this disease will be discussed and the need for a multi-pronged and multi-centre engagement to enhance our understanding of keratoconus will be highlighted.
Design
KIC has been established to address the gaps in our understanding of keratoconus with the aim of collecting baseline as well as longitudinal data on several fields.
Participants
Keratoconus and control (no corneal condition) subjects from different sites globally will be recruited in the study.
Methods
KIC collects data using an online, secure database, which enables standardised data collection at member sites. Data fields collected include medical history, clinical features, quality of life and economic burden questionnaires and possible genetic sample collection from patients of different ethnicities across different geographical locations.
Results
There are currently 40 Australian and international clinics or hospital departments who have joined the KIC. Baseline data has so far been collected on 1130 keratoconus patients and indicates a median age of 29.70 years with 61% being male. A total of 15.3% report a positive family history of keratoconus and 57.7% self-report a history of frequent eye rubbing.
Conclusion
The strength of this consortium is its international, collaborative design and use of a common data collection tool. Inclusion and analyses of cross-sectional and longitudinal data will help answer many questions that remain in keratoconus, including factors affecting progression and treatment outcomes.
Journal Article
Dermoscopy of molluscum contagiosum
Molluscum contagiosum is a common benign viral infection affecting children, sexually active adults, and immunocompromised individuals. We present the case of a 28-year-old male with advanced HIV who developed scattered pink papules over a 2-year period. Through clinical, dermoscopic, and histopathologic evaluations, a diagnosis of molluscum contagiosum was eventually confirmed. Dermoscopy revealed numerous whitish round to polylobular amorphous structures with visible branching vessels. Histopathologic examination showed cup-shaped inverted lobules of hyperplastic squamous epithelium with eosinophilic intracytoplasmic inclusion bodies. This case highlights the importance of dermoscopy in the accurate diagnosis of molluscum contagiosum in immunocompromised patients, reinforcing its role as a non-invasive diagnostic tool in dermatology.
Journal Article
Impact of Immune-Related Adverse Events on Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Hepatocellular Carcinoma
Introduction: Development of immune-related adverse events (irAEs) has been associated with enhanced efficacy with the use of immune checkpoint inhibitors (ICIs). It remains unknown whether such an association exists in advanced hepatocellular carcinoma (aHCC). This study aims to evaluate the association between irAEs and ICI efficacy in patients with aHCC. Methods: We performed a retrospective cohort study on patients with aHCC who received at least one dose of an ICI between May 2015 and November 2019 at the National Cancer Centre Singapore. The primary study objectives were to compare the overall survival (OS) and progression-free survival (PFS) between patients with and without irAEs. Complementary multivariable landmark analyses were performed at the 6-week and 12-week landmarks. Data cutoff was December 31, 2020. Results: One hundred and sixty-eight patients were included. Median age was 69 years, 85.7% were male, 57.7% had hepatitis B infection, 60.7% had ECOG 0, and 78.0% had Child-Pugh A liver cirrhosis. 82.7% received ICI monotherapy, while 17.3% received ICI in combination. Development and severity of irAE were correlated with survival. The median PFS for grade ≥3 irAE versus grades 1–2 irAE versus no irAE was 8.5 versus 3.6 versus 1.3 mths (p < 0.001). The median OS for grade ≥3 irAE versus grades 1–2 irAE versus no irAE was 26.9 versus 14.0 versus 4.6 mths (p < 0.001). Patients with ≥2 irAEs had a significantly longer OS on multivariable analysis (adjusted hazard ratio [aHR]0.35, p < 0.001). The presence of grade ≥3 irAEs was associated with a significantly longer OS on the multivariable analysis at the 6-week landmark (aHR0.34, p = 0.030) and 12-week landmark (aHR0.28, p = 0.011). The use of systemic corticosteroids in patients with irAE was associated with a trend toward a longer OS (20.7 vs. 14.3 mths, p = 0.064). Conclusion: Our study suggests that the presence of all-grade irAEs may be a potential prognostic biomarker in patients with aHCC treated with ICI. Patients with more severe irAEs and multisystem involvement have better prognosis. The prompt use of systemic corticosteroids to treat patients with irAEs is key to ensure the best long-term outcomes for these patients.
Journal Article
Robust SNP-based prediction of rheumatoid arthritis through machine-learning-optimized polygenic risk score
Background
The popular statistics-based Genome-wide association studies (GWAS) have provided deep insights into the field of complex disorder genetics. However, its clinical applicability to predict disease/trait outcomes remains unclear as statistical models are not designed to make predictions. This study employs statistics-free machine-learning (ML)-optimized polygenic risk score (PRS) to complement existing GWAS and bring the prediction of disease/trait outcomes closer to clinical application. Rheumatoid Arthritis (RA) was selected as a model disease to demonstrate the robustness of ML in disease prediction as RA is a prevalent chronic inflammatory joint disease with high mortality rates, affecting adults at the economic prime. Early identification of at-risk individuals may facilitate measures to mitigate the effects of the disease.
Methods
This study employs a robust ML feature selection algorithm to identify single nucleotide polymorphisms (SNPs) that can predict RA from a set of training data comprising RA patients and population control samples. Thereafter, selected SNPs were evaluated for their predictive performances across 3 independent, unseen test datasets. The selected SNPs were subsequently used to generate PRS which was also evaluated for its predictive capacity as a sole feature.
Results
Through robust ML feature selection, 9 SNPs were found to be the minimum number of features for excellent predictive performance (AUC > 0.9) in 3 independent, unseen test datasets. PRS based on these 9 SNPs was significantly associated with (P < 1 × 10
–16
) and predictive (AUC > 0.9) of RA in the 3 unseen datasets. A RA ML-PRS calculator of these 9 SNPs was developed (
https://xistance.shinyapps.io/prs-ra/
) to facilitate individualized clinical applicability. The majority of the predictive SNPs are protective, reside in non-coding regions, and are either predicted to be potentially functional SNPs (pfSNPs) or in high linkage disequilibrium (r2 > 0.8) with un-interrogated pfSNPs.
Conclusions
These findings highlight the promise of this ML strategy to identify useful genetic features that can robustly predict disease and amenable to translation for clinical application.
Journal Article
The impact of diabetes mellitus on treatment and outcomes of rheumatoid arthritis at 5-year follow-up: results from a multi-ethnic Asian cohort
Objectives
We evaluated the impact of type 2 diabetes mellitus (T2DM) on RA treatment and outcomes in a longitudinal RA cohort.
Methods
We analysed data collected in the period 2001–2013 involving 583 RA patients, including demographics, diabetes diagnosis, clinical features, treatment, ACR functional class, HAQ, and quality-of-life measurement using the Short‐Form 36.
Results
Seventy-seven (13.2%) of the RA patients had T2DM. DAS28 was not different in patients with T2DM at 5 years post-RA diagnosis. Fewer T2DM patients received MTX than those without T2DM (51% vs 80%, P < 0.001). Using univariate analysis, T2DM patients were more likely to experience poorer outcomes in terms of ACR functional status (P = 0.009), joint surgery (P = 0.007), knee arthroplasty (P < 0.001) and hospital admissions (P = 0.006). Multivariate regression analyses showed more knee arthroplasty (P = 0.047) in patients with T2DM.
Conclusion
Fewer patients with T2DM received MTX compared with those without T2DM. Patients with RA and T2DM were at higher risk of knee arthroplasty than RA patients without T2DM.
Journal Article
Development, validation, and reliability testing of the College Perspectives around Food Insecurity survey
The objective of this study was to develop and to test the validity and reliability of a survey aimed to evaluate internal and external factors associated with college food insecurity. Researchers used a mixed methods approach to evaluate the College Perspectives around Food Insecurity survey. Survey items were constructed from interview data and assigned a social cognitive theory concept (environment, personal, or behavior). Two rounds of expert reviews established content validity (Round 1, n = 3; Round 2, n = 2). Researchers evaluated face validity through two rounds of cognitive interviews with college students 18+ years old (Round 1, n = 9; Round 2, n = 16) and tested survey reliability (n = 105). Researchers used descriptive statistics, test-retest reliability statistics, and Cronbach’s alpha scores for data analysis. The initial survey contained 143 items. After feedback from expert reviewers and cognitive interviews, the final survey contained 99 items. Test-retest reliability was 0.99, and Cronbach’s alpha scores were 0.74 for environment, 0.47 for personal, and 0.39 for behavior. The College Perspectives around Food Insecurity survey can be used to better understand internal and external factors associated with food insecurity in college students, which can inform interventions aimed at assisting this population.
Journal Article
