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.
View Article and Find Full Text PDFGenome-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.
View Article and Find Full Text PDFPurpose: 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.
View Article and Find Full Text PDFBackground 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.
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.
View Article and Find Full Text PDFIntroduction: 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.
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.
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.
View Article and Find Full Text PDFBackground & 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.
View Article and Find Full Text PDFPhotosensitization 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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFIntroduction: 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.
Background: The prevalence of hidradenitis suppurativa (HS) is 0.00033% to 4.10% globally.
View Article and Find Full Text PDFMajor 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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFCell Stem Cell
March 2023
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.
View Article and Find Full Text PDFBackground: 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.
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.
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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