Publications by authors named "Keith Leung"

Unlabelled: Grip strength measurement, as a surrogate of sarcopenia diagnosis, effectively predicts secondary fracture risk in distal radius fracture patients. This simple tool enhances clinical practice by identifying high-risk patients for targeted interventions, potentially preventing or reversing functional decline and recurrent fractures.

Purpose: To evaluate grip strength and hand muscle cross-sectional area as predictors of secondary fracture risk in patients with a history of distal radius fracture (DRF), serving as surrogates of the diagnosis of sarcopenia.

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Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear. Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis.

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Fms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g.

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Theoretical accounts posit a close link between speech perception and production, but empirical findings on this relationship are mixed. To explain this apparent contradiction, a proposed view is that a perception-production relationship should be established through the use of critical perceptual cues. This study examines this view by using Mandarin tones as a test case because the perceptual cues for Mandarin tones consist of perceptually critical pitch direction and noncritical pitch height cues.

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  • - The study focuses on the role of Methyltransferase 16 (METTL16) in liver cancer stem cells (CSCs), revealing its significant involvement in the development and maintenance of hepatocellular carcinoma (HCC) while having a lesser effect on normal liver development.
  • - Using various experimental models, the researchers found that depleting METTL16 reduced CSC frequency and hindered HCC initiation and progression, indicating METTL16's essential role in cancer biology.
  • - The research highlights METTL16 as a key regulator of ribosomal RNA maturation and mRNA translation, identifying eIF3a as a target, providing insights for potential therapeutic developments against liver cancer.
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Clearly enunciated speech (relative to conversational, plain speech) involves articulatory and acoustic modifications that enhance auditory-visual (AV) segmental intelligibility. However, little research has explored clear-speech effects on the perception of suprasegmental properties such as lexical tone, particularly involving visual (facial) perception. Since tone production does not primarily rely on vocal tract configurations, tones may be less visually distinctive.

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  • mRNA methylation, specifically methyladenosine (mA), plays a crucial role in regulating gene expression and is linked to various processes, including cancer development.
  • The study identifies YTHDF2 as being overexpressed in acute myeloid leukemia (AML) patients, where it promotes the maturation of the miR-126-3p, a microRNA associated with cancer progression in AML.
  • Findings suggest that targeting the YTHDF2/miR-126 pathway could be a potential therapeutic strategy for treating AML, highlighting the role of mA in miRNA processing and tumorigenesis.
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  • * The lack of TET2 leads to increased expression of Tetraspanin 13 (TSPAN13), which activates CXCR4/CXCL12 signaling, enhancing LSC migration into the bone marrow and sustaining their growth.
  • * TET2 deficiency causes changes in TSPAN13 mRNA, making it more stable due to specific recognition of methyl modifications, highlighting TET2's role as a demethylase involved in AML progression and LSC behavior.
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  • N-methylguanosine (mG) modification is found not only at the mRNA 5' cap but also internally in mRNAs, and its specific role remains unclear.
  • Recent research shows that internal mG is recognized by Quaking proteins (QKIs), with over 1,000 mRNA targets identified that feature a specific "GANGAN" motif.
  • QKI7 interacts with the core protein G3BP1 to transport mG-modified transcripts into stress granules, influencing mRNA stability and translation, particularly affecting cancer cell responses to chemotherapy.
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Familial hypercholesterolemia (FH) is a hereditary condition caused by mutations in the lipid pathway. The goal in managing FH is to reduce circulating low-density lipoprotein cholesterol and, therefore, reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Because FH patients were considered high risk groups due to an increased susceptible for contracting COVID-19 infection, we hypothesized whether the effects of the pandemic hindered access to cardiovascular care.

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  • Although childhood B cell acute lymphoblastic leukemia (B-ALL) has an over 80% survival rate, the prognosis drops to 30% for older or relapsed patients, necessitating better treatments.
  • This study identifies the TET1 protein, which is overexpressed in B-ALL and functions as an oncogene, as it can transform normal B cells into leukemia in mice.
  • Targeting TET1 signaling through pharmacological inhibitors shows promise in reducing B-ALL cell viability and progression, particularly when combined with other treatments like AZD0156 and vincristine.
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Background And Objectives: Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females.

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  • N-methyladenosine (mA) is a key modification in mammalian mRNAs and is linked to various diseases, including leukemia.
  • Researchers identified METTL16 as a crucial gene for the survival of acute myeloid leukemia (AML) cells, finding it is overexpressed in human AML and especially prevalent in leukemia stem cells.
  • The study reveals that depleting METTL16 hampers AML development and stem cell self-renewal, largely by altering the metabolism of branched-chain amino acids (BCAAs) through the regulation of enzymes BCAT1 and BCAT2, positioning METTL16 as a significant player in leukemia progression.
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Introduction: The presence of multiple comorbidities increases the risk of all-cause mortality, but the effects of the comorbidity sequence before the baseline date on mortality remain unexplored. This study investigated the relationship between coronary heart disease (CHD), atrial fibrillation (AF) and heart failure (HF) through their sequence of development and the effect on all-cause mortality risk in type 2 diabetes mellitus. Methods: This study included patients with type 2 diabetes mellitus prescribed antidiabetic/cardiovascular medications in public hospitals of Hong Kong between 1 January 2009 and 31 December 2009, with follow-up until death or 31 December 2019.

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  • The spiked helmet sign (SHS), an ECG pattern associated with poor outcomes, was first identified in 2011, prompting a study to evaluate its characteristics and clinical outcomes based on existing literature.
  • A total of 39 patients from 26 case reports were examined, finding that the most common associated conditions included intracranial hemorrhages and pneumothorax, with many patients facing multiple complications.
  • Of the 32 patients whose outcomes were reported, 59% died during hospitalization, emphasizing the need for clinicians to quickly recognize SHS and assess for underlying issues, alongside calls for more extensive research on its prevalence and implications.
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Introduction: Neutrophil-to-lymphocyte ratio (NLR) is a routinely available biomarker that reflects systemic inflammation. The study evaluated the predictive value of NLR for ischemic stroke and atrial fibrillation (AF) in patients with type 2 diabetes mellitus.

Methods: This was a population-based cohort study of patients with type 2 diabetes mellitus and complete blood count tests at baseline between 1 January 1st, 2009, and 31 December, 2009, at government-funded hospitals/clinics in Hong Kong.

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The in vivo mechanisms underlying dominant syndromes caused by mutations in SRY-Box Transcription Factor 9 () and () transcription factors, when they either are expressed alone or are coexpressed, are ill-defined. We created a mouse model for the campomelic dysplasia mutation, which truncates the transactivation domain but leaves DNA binding and dimerization intact. Here, we find that causes deafness via distinct mechanisms in the endolymphatic sac (ES)/duct and cochlea.

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Objectives: To assess the effect of vasopressin, steroid and epinephrine (VSE) combination therapy on return of spontaneous circulation (ROSC) after in-hospital cardiac arrest (IHCA), and test the conclusiveness of evidence using trial sequential analysis (TSA).

Methods: The systematic search included PubMed, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) that included adult patients with IHCA, with at least one group receiving combined VSE therapy were selected.

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  • The study investigates the role of the mA reader YTHDC1 in promoting metastasis in triple negative breast cancer (TNBC) and its impact on gene expression.
  • Researchers utilized various sequencing methods and a mammary fat pad mouse model to show that higher levels of YTHDC1 correlate with poor patient prognosis and increased lung metastasis of TNBC cells.
  • The findings reveal that YTHDC1 is crucial in regulating TGF-β signaling and the expression of the SMAD3 gene, which is linked to cell migration and invasion in TNBC.
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Background: This study examined the clinical characteristics, genetic basis, healthcare utilisation and costs of catecholaminergic ventricular tachycardia (CPVT) patients from a Chinese city.

Methods: This was a territory-wide retrospective cohort study of consecutive CPVT patients at public hospitals or clinics in Hong Kong. Healthcare resource utilisation for accident and emergency (A&E), inpatient and outpatient attendances were analysed over 19 years (2001-2019) followed by calculations of annualised costs (in USD).

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Background: The long-term prognosis of the cardio-metabolic and renal complications, in addition to mortality in patients with newly diagnosed pulmonary hypertension, are unclear. This study aims to develop a scalable predictive model in the form of an electronic frailty index (eFI) to predict different adverse outcomes.

Methods: This was a population-based cohort study of patients diagnosed with pulmonary hypertension between January 1st, 2000 and December 31st, 2017, in Hong Kong public hospitals.

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Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a hereditary disease characterized by fibrofatty infiltration of the right ventricular myocardium that predisposes affected patients to malignant ventricular arrhythmias, dual-chamber cardiac failure and sudden cardiac death (SCD). The present study aims to investigate the risk of detrimental cardiovascular events in an Asian population of ARVC/D patients, including the incidence of malignant ventricular arrhythmias, new-onset heart failure with reduced ejection fraction (HFrEF), as well as long-term mortality.

Methods And Results: This was a territory-wide retrospective cohort study of patients diagnosed with ARVC/D between 1997 and 2019 in Hong Kong.

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Introduction: Cancer patients may be susceptible to poorer outcomes in COVID-19 infection owing to the immunosuppressant effect of chemotherapy/radiotherapy and cancer growth, along with the potential for nosocomial transmission due to frequent hospital admissions.

Methods: This was a population-based retrospective cohort study of COVID-19 patients who presented to Hong Kong public hospitals between 1 January 2020 and 8 December 2020. The primary outcome was a composite endpoint of requirement for intubation, ICU admission and 30-day mortality.

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  • This study evaluates the effectiveness of store-and-forward tele-ophthalmology for diagnosing cataracts, glaucoma, and age-related macular degeneration in patients over 40 with vision impairment lasting three months or more.
  • The research involved comparing tele-ophthalmology results with traditional face-to-face assessments and used statistical measures to determine agreement and accuracy between the two methods.
  • Findings indicated that tele-ophthalmology matched in accuracy, particularly excelling in diagnosing AMD with over 99% sensitivity and specificity, while also showing solid performance with cataracts and glaucoma, and both modalities incurred similar costs.
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