An E2 ubiquitin-conjugating enzyme links diubiquitinated H2B to H3K27M oncohistone function.

The H3K27M oncogenic histone (oncohistone) mutation drives ~80% of incurable childhood brain tumors known as diffuse midline gliomas (DMGs). The major molecular feature of H3K27M mutant DMGs is a global loss of H3K27 trimethylation (H3K27me3), a phenotype conserved in (). Here, we perform unbiased genome-wide suppressor screens in expressing H3K27M and isolate 20 suppressors, all of which at least partially restore H3K27me3.

Automatic retinal image analysis methods using colour fundus images for screening glaucomatous optic neuropathy.

Objectives: Train an automatic retinal image analysis (ARIA) method to screen glaucomatous optic neuropathy (GON) on non-mydriatic retinal images labelled with the additional results of optical coherence tomography (OCT) and assess different models for the GON classification.

Methods: All the images were obtained from the hospital for training and 10-fold cross-validation. Two methods were used to improve the classification performance: (1) using images labelled with the additional results of OCT as the reference standard and (2) generating models using retinal features from the entire images, the region of interest (ROI) of the optic disc, and the ROI of the macula, and the combination of all the features.

Comparison of macular thickness in diabetic patients acquired from optical coherence tomography mode and optical coherence tomography angiography mode in Cirrus HD-OCT 5000.

Purpose: To compare macular thickness obtained using two different modes of image acquisitions with Cirrus HD-OCT 5000.

Methods: Patients with diabetes were recruited and macular thickness were obtained using optical coherence tomography (OCT) mode and optical coherence tomography angiography (OCTA) mode. The OCT mode involved a Macular Cube (512×128 pixels) centred on the fovea covering a 6 × 6 mm macular region.

Evaluating the impact of sugar-sweetened beverages tax on overweight, obesity, and type 2 diabetes in an affluent Asian setting: A willingness-to-pay survey and simulation analysis.

Background: The potential health effects of taxing sugar-sweetened beverages (SSBs) has been insufficiently examined in Asian contexts. This study aimed to assess the impact of SSB taxation on the prevalence of obesity/overweight and type 2 diabetes mellitus (T2DM) in Hong Kong using a willingness-to-pay (WTP) survey and simulation analysis.

Methods: A random telephone survey was conducted with 1000 adults from May to June 2020.

Projection of dengue fever transmissibility under climate change in South and Southeast Asian countries.

Vector-borne infectious disease such as dengue fever (DF) has spread rapidly due to more suitable living environments. Considering the limited studies investigating the disease spread under climate change in South and Southeast Asia, this study aimed to project the DF transmission potential in 30 locations across four South and Southeast Asian countries. In this study, weekly DF incidence data, daily mean temperature, and rainfall data in 30 locations in Singapore, Sri Lanka, Malaysia, and Thailand from 2012 to 2020 were collected.

Multi-domain neurocognitive impairment following definitive intensity-modulated radiotherapy for nasopharyngeal cancer: A cross-sectional study.

Introduction: Neurocognitive impairment from inadvertent brain irradiation is common following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to determine the prevalence, pattern, and radiation dose-toxicity relationship of this late complication.

Materials And Methods: We undertook a cross-sectional study of 190 post-IMRT NPC survivors.

Genetic association of COVID-19 severe versus non-severe cases by RNA sequencing in patients hospitalised in Hong Kong.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused extensive disruption of public health worldwide. There were reports of COVID-19 patients having multiple complications. This study investigated COVID-19 from a genetic perspective.

Plasma Epstein-Barr Virus DNA and Risk of Future Nasopharyngeal Cancer.

BACKGROUND: We previously conducted a prospective study to show that nasopharyngeal cancer (NPC) screening with circulating Epstein–Barr virus (EBV) DNA analysis can improve survival. However, the long-term significance of positive results in individuals without cancer was unclear. METHODS: We conducted a second-round screening at a median of 43 months after the initial screening.

Early detection of nasopharyngeal carcinoma: performance of a short contrast-free screening magnetic resonance imaging.

Background: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program.

Methods: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB.

Interpreting the Significance of Changes in Health-Related Quality-of-Life Scores.

Purpose: To determine the significance to patients of changes in health-related quality-of-life (HLQ) scores assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30).

Patients And Methods: A subjective significance questionnaire (SSQ), which asks patients about perceived changes in physical, emotional, and social functioning and in global quality of life (global QL) and the QLQ-C30 were completed by patients who received chemotherapy for either breast cancer or small-cell lung cancer (SCLC). In the SSQ, patients rated their perception of change since the last time they completed the QLQ-C30 using a 7-category scale that ranged from "much worse" through "no change" to "much better.

Mechanistic modeling of empty-full separation in recombinant adeno-associated virus production using anion-exchange membrane chromatography.

Recombinant adeno-associated viral vectors (rAAVs) have become an industry-standard technology in the field of gene therapy, but there are still challenges to be addressed in their biomanufacturing. One of the biggest challenges is the removal of capsid species other than that which contains the gene of interest. In this work, we develop a mechanistic model for the removal of empty capsids-those that contain no genetic material-and enrichment of full rAAV using anion-exchange membrane chromatography.

Enhanced Operational Stability by Cavity Control of Single-Layer Organic Light-Emitting Diodes Based on Thermally Activated Delayed Fluorescence.

Highly efficient organic light-emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) emitters are realized in recent years, but the device lifetime needs further improvement for practical display or lighting applications. In this work, a device design principle is presented by tuning the optical cavity of single-layer undoped devices, to realize efficient and long-lived TADF OLEDs. Extending the cavity length to the second-order interference maximum by increasing the emissive layer thickness broadens the recombination zone, while the optical outcoupling efficiency remains close to that of the thinner first-order devices.

Impact of climate change on dengue fever epidemics in South and Southeast Asian settings: A modelling study.

The potential for dengue fever epidemic due to climate change remains uncertain in tropical areas. This study aims to assess the impact of climate change on dengue fever transmission in four South and Southeast Asian settings. We collected weekly data of dengue fever incidence, daily mean temperature and rainfall from 2012 to 2020 in Singapore, Colombo, Selangor, and Chiang Mai.

Robust time selection for interim analysis in the Bayesian phase 2 exploratory clinical trial.

In phase 2 clinical trials, we expect to make a right Go or No-Go decision during the interim analysis (IA) and make this decision at the right time. The optimal time for IA is usually determined based on a utility function. In most previous research, utility functions aim to minimize the expected sample size or total cost in confirmatory trials.

Cell state-dependent chromatin targeting in NUT carcinoma.

Aberrant transcriptional programming and chromatin dysregulation are common to most cancers. Whether by deranged cell signaling or environmental insult, the resulting oncogenic phenotype is typically manifested in transcriptional changes characteristic of undifferentiated cell growth. Here we analyze targeting of an oncogenic fusion protein, BRD4-NUT, composed of two normally independent chromatin regulators.

Cell state-dependent chromatin targeting in NUT carcinoma.

Aberrant transcriptional programming and chromatin dysregulation are common to most cancers. Whether by deranged cell signaling or environmental insult, the resulting oncogenic phenotype is typically manifested in transcriptional changes characteristic of undifferentiated cell growth. Here we analyze targeting of an oncogenic fusion protein, BRD4-NUT, composed of 2 normally independent chromatin regulators.

Reduced bimolecular charge recombination in efficient organic solar cells comprising non-fullerene acceptors.

Bimolecular charge recombination is one of the most important loss processes in organic solar cells. However, the bimolecular recombination rate in solar cells based on novel non-fullerene acceptors is mostly unclear. Moreover, the origin of the reduced-Langevin recombination rate in bulk heterojunction solar cells in general is still poorly understood.

Lifestyle Changes Reduced Estimated White Matter Hyperintensities Based on Retinal Image Analysis.

This study evaluates if there is an association between lifestyle changes and the risk of small vessel disease (SVD) as measured by cerebral white matter hyperintensities (WMH) estimated by the automatic retinal image analysis (ARIA) method. We recruited 274 individuals into a community cohort study. Subjects were assessed at baseline and annually with the Health-Promoting Lifestyle Profile II Questionnaire (HPLP-II) and underwent a simple physical assessment.

An efficient approach to estimate the risk of coronary artery disease for people living with HIV using machine-learning-based retinal image analysis.

Background: People living with HIV (PLWH) have increased risks of non-communicable diseases, especially cardiovascular diseases. Current HIV clinical management guidelines recommend regular cardiovascular risk screening, but the risk equation models are not specific for PLWH. Better tools are needed to assess cardiovascular risk among PLWH accurately.

The mechanism shaping the logistic growth of mutation proportion in epidemics at population scale.

Virus evolution is a common process of pathogen adaption to host population and environment. Frequently, a small but important fraction of virus mutations are reported to contribute to higher risks of host infection, which is one of the major determinants of infectious diseases outbreaks at population scale. The key mutations contributing to transmission advantage of a genetic variant often grow and reach fixation rapidly.

Digital solution for detection of undiagnosed diabetes using machine learning-based retinal image analysis.

Introduction: Undiagnosed diabetes is a global health issue. Previous studies have estimated that about 24.1%-75.

A Prism Vote method for individualized risk prediction of traits in genotype data of Multi-population.

Multi-population cohorts offer unprecedented opportunities for profiling disease risk in large samples, however, heterogeneous risk effects underlying complex traits across populations make integrative prediction challenging. In this study, we propose a novel Bayesian probability framework, the Prism Vote (PV), to construct risk predictions in heterogeneous genetic data. The PV views the trait of an individual as a composite risk from subpopulations, in which stratum-specific predictors can be formed in data of more homogeneous genetic structure.

Impact of extreme weather on dengue fever infection in four Asian countries: A modelling analysis.

The rapid spread of dengue fever (DF) infection has posed severe threats to global health. Environmental factors, such as weather conditions, are believed to regulate DF spread. While previous research reported inconsistent change of DF risk with varying weather conditions, few of them evaluated the impact of extreme weather conditions on DF infection risk.