Publications by authors named "Seah C"

Background/objectives: Glioblastoma (GBM) is the most common malignant primary central nervous system tumor with extremely poor prognosis and survival outcomes. Non-invasive methods like radiomic feature extraction, which assess sub-visual imaging features, provide a potentially powerful tool for distinguishing molecular profiles across groups of patients with GBM. Using consensus clustering of MRI-based radiomic features, this study aims to investigate differential gene expression profiles based on radiomic clusters.

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Genome-wide association studies identify common genomic variants associated with disease across a population. Individual environmental effects are often not included, despite evidence that environment mediates genomic regulation of higher order biology. Body mass index (BMI) is associated with complex disorders across clinical specialties, yet has not been modeled as a genomic environment.

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Purpose: Meningiomas are central nervous system tumors whose incidence increases with age. Benign meningioma pathogenesis involves germline or somatic mutation of target genes, such as NF2, leading to clonal expansion. We used an established cancer epidemiology model to investigate the number of rate-limiting steps sufficient for benign meningioma development.

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Background Context: Degenerative cervical myelopathy (DCM) is a progressive spinal condition that can lead to severe neurological dysfunction. Despite its degenerative pathophysiology, family history has shown to be a largely important factor in incidence and progression, suggesting that inherent genetic predisposition may play a role in pathophysiology.

Purpose: To determine the tissue-specific, functional genetic basis of hereditary predisposition to cervical myelopathy.

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Psychological trauma has profound effects on brain function and precipitates psychiatric disorders in vulnerable individuals, however, the molecular mechanisms linking trauma with psychiatric risk remain incompletely understood. Using RNA-seq data postmortem brain tissue of a cohort of 304 donors (N=136 with trauma exposure), we investigated transcriptional signatures of trauma exposures in two cortical regions (dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex) and two amygdala regions (medial amygdala and basolateral amygdala) associated with stress processing and regulation. We focused on dissecting heterogeneity of traumatic experiences in these transcriptional signatures by investigating exposure to several trauma types (childhood, adulthood, complex, single acute, combat, and interpersonal traumas) and interactions with sex.

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Introduction: We presented the key findings from Singapore's Changi General Hospital Breast Centre's lymphedema surveillance strategy that used patients' reported symptoms, standard arm circumference measurements and clinical assessment in the diagnosis of breast cancer-related lymphedema (BCRL). Our secondary aim was to highlight and discuss important elements of a surveillance strategy that can be implemented to track this outcome measure of breast cancer treatment for future research.

Method: We conducted a cross-sectional study of 511 breast cancer patients to assess the prevalence of BCRL and its associated risk factors.

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Background: Chronic pain affects one fifth of American adults, contributing significant public health burden. Chronic pain mechanisms can be further understood through investigating brain gene expression.

Methods: We tested differentially expressed genes (DEGs) in chronic pain, migraine, lifetime fentanyl and oxymorphone use, and with chronic pain genetic risk in four brain regions (dACC, DLPFC, MeA, BLA) and imputed cell type expression data from 304 postmortem donors.

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The overproduction of the toxic peptide amyloid-beta (Aβ) generated from the cleavage of amyloid precursor protein (APP) is proposed to be a critical event in the development of Alzheimer's disease. Evidence suggests that the cleavage of APP occurs after its internalization from the cell surface. Previously, we identified a novel pathway for APP internalization, which trafficks cell surface APP directly to lysosomes by macropinocytosis, leading to its processing into Aβ.

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Article Synopsis
  • PTSD genetics have been difficult to study compared to other psychiatric disorders, limiting our biological understanding of the condition.
  • A large-scale meta-analysis involving over 1.2 million individuals identified 95 genome-wide significant loci, with 80 being new discoveries related to PTSD.
  • Researchers identified 43 potential causal genes linked to neurotransmitter activity, developmental processes, synaptic function, and immune regulation, enhancing our knowledge of the neurobiological systems involved in PTSD.
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Background & Aims: Hepatitis B surface antigen (HBsAg) loss or functional cure (FC) is considered the optimal therapeutic outcome for patients with chronic hepatitis B (CHB). However, the immune-pathological biomarkers and underlying mechanisms of FC remain unclear. In this study we comprehensively interrogate disease-associated cell states identified within intrahepatic tissue and matched PBMCs (peripheral blood mononuclear cells) from patients with CHB or after FC, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC.

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Article Synopsis
  • The study investigates why people react differently to the same stressors by examining how stress affects gene expression related to brain disorders.
  • Researchers identified over 8,500 genetic variants that interact with stress and can disrupt the expression of genes associated with brain disorders, specifically in certain brain regions and cell types.
  • The findings highlight the importance of considering stress in genetic studies of brain disorders, suggesting that this approach could enhance diagnosis, treatment, and drug development.
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Photosensitization was developed as a risk-reduction strategy against the contamination by environmental mold spores during the bread cooling phase. Two food-grade photosensitizers -chlorophyllin (CHL) and riboflavin (RBF), were used to evaluate the effect of visible (blue) LED illumination against three common bread spoilage molds. Aided by CHL, 405 nm LEDs inactivated Rhizopus stolonifer and Penicillium expansum by 77.

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Background: Providing high-quality early childhood care and education is understood as key to maximizing children's potential to succeed later in life, as it stimulates young children's development of skills and competencies needed to promote optimal outcomes and success later in life. Despite the government's efforts to support the early childhood sector, educators in Singapore continue to report difficulties in implementing practices in classrooms that promote children's social, emotional, and cognitive development. To enhance educators' skills in these domains, we developed the Enhancing And Supporting Early development to better children's Lives (EASEL) Approach, a set of universal, educator-delivered practices for use with 3-6-year-old children in early childhood settings to improve social, emotional, behavioral, and executive functioning (SEB+EF) outcomes.

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Article Synopsis
  • PTSD genetics are harder to study compared to other mental health disorders, resulting in limited biological insights from past research.
  • A large-scale analysis involving over 1.2 million individuals found 95 significant genetic loci related to PTSD, with 80 being new discoveries.
  • The study identified 43 potential causal genes linked to neurotransmitters, synaptic function, and immune responses, enhancing understanding of PTSD's biological mechanisms and suggesting new research directions.
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Introduction: The most recent local study on the incidence of histological subtypes of all brain and spinal tumours treated surgically was published in 2000. In view of the outdated data, we investigated the presenting characteristics, histological subtypes and outcomes of adult patients who underwent surgery for brain or spinal tumours at our institution.

Methods: A single-centre retrospective review of 501 patients who underwent surgery for brain or spinal tumours from 2016 to 2020 was conducted.

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Major depressive disorder (MDD) is a complex and heterogeneous psychiatric syndrome with genetic and environmental influences. In addition to neuroanatomical and circuit-level disturbances, dysregulation of the brain transcriptome is a key phenotypic signature of MDD. Postmortem brain gene expression data are uniquely valuable resources for identifying this signature and key genomic drivers in human depression; however, the scarcity of brain tissue limits our capacity to observe the dynamic transcriptional landscape of MDD.

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Article Synopsis
  • Genetic studies show that schizophrenia has a complex polygenic risk with many common variants, each contributing only a bit to the overall risk.
  • Researchers found that when four specific schizophrenia risk genes (called eGenes) are disturbed together, they cause unexpected changes in gene expression, especially among genes related to brain function and schizophrenia risk.
  • By studying fifteen eGenes, they discovered that these genes interact in ways that make their combined effects smaller than expected, indicating that understanding their relationships is crucial for predicting schizophrenia outcomes and developing new treatments.
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The integration of microarray technologies and machine learning methods has become popular in predicting the pathological condition of diseases and discovering risk genes. Traditional microarray analysis considers pathways as a simple gene set, treating all genes in the pathway identically while ignoring the pathway network's structure information. This study proposed an entropy-based directed random walk (e-DRW) method to infer pathway activities.

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In this issue, Wells et al. combine genetic multiplexing ("village-in-a-dish") and Stem-cell-derived NGN2-accelerated Progenitors (SNaPs) to evaluate genotype-phenotype relationships across 100 donors in the context of Zika virus infection in the developing brain. This resource will be broadly applicable in uncovering how genetic variation underlies risk for neurodevelopmental disorders.

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Background: Knowledge of the barriers and facilitators in the adoption of digital health interventions (DHI) is sparse yet crucial to facilitate chronic obstructive pulmonary disease (COPD) management.

Objectives: This scoping review aimed to summarize patient- and healthcare provider-level barriers and facilitators in the adoption of DHIs for COPD management.

Methods: Nine electronic databases were searched from inception up till October 2022 for English language evidence.

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Aim And Objective: As rising global prevalence of diabetes burdens an overstrained healthcare system, it would be prudent to employ primary prevention strategies. This review aims to detail characteristics of technology-enabled diabetes prevention programs (t-DPP) and the technology acceptance amongst prediabetic individuals.

Design: A scoping review.

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Aims: Muscleblind-like 2 (MBNL2) plays a crucial role in regulating alternative splicing during development and mouse loss of MBNL2 recapitulates brain phenotypes in myotonic dystrophy (DM). However, the mechanisms underlying DM neuropathogenesis during brain development remain unclear. In this study, we aim to investigate the impact of MBNL2 elimination on neuronal development by Mbnl2 conditional knockout (CKO) mouse models.

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