Publications by authors named "Mak B"

Introduction: Emerging evidence supports mindfulness as a potential psychotherapy for post-traumatic stress disorder (PTSD). Individuals with subthreshold PTSD experience significant impairment in their daily life and functioning due to PTSD symptoms, despite not meeting the full diagnostic criteria for PTSD in DSM-5. Mindfulness skills, including non-judgmental acceptance, attentional control and openness to experiences may help alleviate PTSD symptoms by targeting characteristics such as intensified memory processing, dysregulated hyperarousal, avoidance, and thought suppression.

View Article and Find Full Text PDF

Purpose: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants.

Methods: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells.

Results: Biallelic variants in CRELD1 were found in 18 participants from 14 families.

View Article and Find Full Text PDF

Purpose: To determine prognostic and predictive clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) on the basis of a combination of plasma-derived genomic alterations and lipid features in a longitudinal cohort of patients with advanced prostate cancer.

Methods: A multifeature classifier was constructed to predict clinical outcomes using plasma-based genomic alterations detected in 120 genes and 772 lipidomic species as informative features in a cohort of 71 patients with mHSPC and 144 patients with mCRPC. Outcomes of interest were collected over 11 years of follow-up.

View Article and Find Full Text PDF

Background: Using comprehensive plasma lipidomic profiling from men with metastatic castration-resistant prostate cancer (mCRPC), we have previously identified a poor-prognostic lipid profile associated with shorter overall survival (OS). In order to translate this biomarker into the clinic, these men must be identifiable via a clinically accessible, regulatory-compliant assay.

Methods: A single regulatory-compliant liquid chromatography-mass spectrometry assay of candidate lipids was developed and tested on a mCRPC Discovery cohort of 105 men.

View Article and Find Full Text PDF

Despite key advances in the treatment of prostate cancer (PCa), a proportion of men have resistance, and all will develop resistance to current therapeutics over time. Aberrant lipid metabolism has long been associated with prostate carcinogenesis and progression, but more recently there has been an explosion of preclinical and clinical data which is informing new clinical trials. This review explores the epidemiological links between obesity and metabolic syndrome and PCa, the evidence for altered circulating lipids in PCa and their potential role as biomarkers, as well as novel therapeutic strategies for targeting lipids in men with PCa, including therapies widely used in cardiovascular disease such as statins, metformin and lifestyle modification, as well as novel targeted agents such as sphingosine kinase inhibitors, DES1 inhibitors and agents targeting FASN and beta oxidation.

View Article and Find Full Text PDF

Elevated circulating sphingolipids are associated with shorter overall survival and therapeutic resistance in metastatic castration-resistant prostate cancer (mCRPC), suggesting that perturbations in sphingolipid metabolism promotes prostate cancer growth. This study assessed whether addition of simvastatin to standard treatment for mCRPC can modify a poor prognostic circulating lipidomic profile represented by a validated 3-lipid signature (3LS). Men with mCRPC (n = 27) who were not on a lipid-lowering agent, were given simvastatin for 12 weeks (40 mg orally, once daily) with commencement of standard treatment.

View Article and Find Full Text PDF

Variants in RAC3, encoding a small GTPase RAC3 which is critical for the regulation of actin cytoskeleton and intracellular signal transduction, are associated with a rare neurodevelopmental disorder with structural brain anomalies and facial dysmorphism. We investigated a cohort of 10 unrelated participants presenting with global psychomotor delay, hypotonia, behavioural disturbances, stereotyped movements, dysmorphic features, seizures and musculoskeletal abnormalities. MRI of brain revealed a complex pattern of variable brain malformations, including callosal abnormalities, white matter thinning, grey matter heterotopia, polymicrogyria/dysgyria, brainstem anomalies and cerebellar dysplasia.

View Article and Find Full Text PDF
Article Synopsis
  • The study aims to assess the effectiveness and safety of intermittent docetaxel chemotherapy guided by plasma levels of methylated glutathione S-transferase Pi-1 in men with metastatic castration-resistant prostate cancer (CRPC).
  • It involves a randomized phase-2 trial with 120 patients across six Australian centers, where participants will be pre-screened based on their methylated levels before and during treatment.
  • The primary outcome is radiographic progression-free survival, while secondary outcomes include patient safety, overall survival, and treatment costs, with results expected to provide insights on using the biomarker for treatment decisions.
View Article and Find Full Text PDF

Background: Both changes in circulating lipids represented by a validated poor prognostic 3-lipid signature (3LS) and somatic tumour genetic aberrations are individually associated with worse clinical outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). A key question is how the lipid environment and the cancer genome are interrelated in order to exploit this therapeutically. We assessed the association between the poor prognostic 3-lipid signature (3LS), somatic genetic aberrations and clinical outcomes in mCRPC.

View Article and Find Full Text PDF

Background: Intrinsic resistance to androgen receptor signalling inhibitors (ARSI) occurs in 20-30% of men with metastatic castration-resistant prostate cancer (mCRPC). Ceramide metabolism may have a role in ARSI resistance. Our study's aim is to investigate the association of the ceramide-sphingosine-1-phosphate (ceramide-S1P) signalling axis with ARSI resistance in mCRPC.

View Article and Find Full Text PDF

Objective: Despite the implementation of quality assurance procedures, current clinical trial management processes are time-consuming, costly, and often susceptible to error. This can result in limited trust, transparency, and process inefficiencies, without true patient empowerment. The objective of this study was to determine whether blockchain technology could enforce trust, transparency, and patient empowerment in the clinical trial data management process, while reducing trial cost.

View Article and Find Full Text PDF

Associated particle imaging (API) is a non-destructive nuclear technique for the 3D determination of isotopic distributions. By detecting the alpha particle associated with the emitted neutron in the deuterium-tritium fusion reaction with a position- and time-resolving detector, the direction of the 14.1 MeV neutron and its time of emission can be determined.

View Article and Find Full Text PDF

Serine-arginine (SR) protein kinases (SRPKs) regulate the functions of the SR-rich splicing factors by phosphorylating multiple serines within their C-terminal arginine-serine-rich domains. Dysregulation of these phosphorylation events has been implicated in many diseases, suggesting SRPKs are potential therapeutic targets. In particular, aberrant SRPK1 expression alters the balances of proangiogenic (VEGF) and antiangiogenic (VEGFb) splicing isoforms of the key angiogenesis factor, vascular endothelial growth factor (VEGF), through the phosphorylation of prototypic SR protein SRSF1.

View Article and Find Full Text PDF

3q29 deletion syndrome (3q29del) is a recurrent deletion syndrome associated with neuropsychiatric disorders and congenital anomalies. Dysmorphic facial features have been described but not systematically characterized. This study aims to detail the 3q29del craniofacial phenotype and use a machine learning approach to categorize individuals with 3q29del through analysis of 2D photos.

View Article and Find Full Text PDF

Glutamine is a critical nutrient in cancer; however, its contribution to purine metabolism in prostate cancer has not previously been determined. Guanosine monophosphate synthetase (GMPS) acts in the de novo purine biosynthesis pathway, utilizing a glutamine amide to synthesize the guanine nucleotide. This study demonstrates that GMPS mRNA expression correlates with Gleason score in prostate cancer samples, while high GMPS expression was associated with decreased rates of overall and disease/progression-free survival.

View Article and Find Full Text PDF

Background: Dysregulated lipid metabolism is associated with more aggressive pathology and poorer prognosis in prostate cancer (PC). The primary aim of the study is to assess the relationship between the plasma lipidome and clinical outcomes in localised and metastatic PC. The secondary aim is to validate a prognostic circulating 3-lipid signature specific to metastatic castration-resistant PC (mCRPC).

View Article and Find Full Text PDF

Purpose: To identify the approximately 12% with inherited cancer predisposition, all men with metastatic prostate cancer (mPC) should be offered germline genetic testing. This guides treatment choices and impacts cancer prevention in the family. Limited genetic services globally present a barrier to testing.

View Article and Find Full Text PDF

A lack of knowledge about mental health and stigma of the mentally ill are barriers to the treatment of mental disorders. To reduce these barriers, anti-stigma campaigns using a knowledge contact approach were launched to raise public mental health knowledge by education and to reduce stigma by encouraging contact with individuals with mental disorders. The current study attempted to investigate the outcome of a knowledge contact-based programme in adolescents and adults in the Hong Kong Chinese population.

View Article and Find Full Text PDF

Surface bound guidance cues and gradients are vital for directing cellular processes during development and repair. In vivo, these cues are often presented within a soft extracellular matrix with elastic moduli E < 10 kPa, but in vitro haptotaxis experiments have been conducted primarily on hard substrates with elastic moduli in the MPa to GPa range. Here, a technique is presented for patterning haptotactic proteins with nanometer resolution on soft substrates with physiological elasticity.

View Article and Find Full Text PDF

Language teacher's composition rating process has become an issue of growing concern in writing research over the past three decades. It is evident that a substantial number of composition rating research have employed concurrent think-aloud protocol analysis (TAPA) as a major method of qualitative data collection and data analysis. For the previous studies that adopted the method of TAPA in exploring the composition marking process, they were mostly confined to the study on L1/L2 English language education and not much has been done specifically on L1 Chinese language education.

View Article and Find Full Text PDF

There has been no study evaluating whether primary care services are sufficiently oriented towards the older population in Hong Kong, particularly those with increasing frailty. Since primary care is a key first interface in promotion and maintenance of health in older people, an assessment of the age-friendliness of service provisions is of critical importance in optimizing the health of aging populations. The age-friendliness of primary care services for older people was assessed using focus groups of elderly people and also of service providers who care for them.

View Article and Find Full Text PDF

Background: Little is known about patient preferences for selection of chronic hepatitis B (CHB) treatment. This issue is important as it affects the therapeutic choices available for patients and, in the long term, the health of CHB patients.

Methods: The study was a questionnaire-led survey directed at patients attending a CHB follow-up clinic.

View Article and Find Full Text PDF

Entecavir switch is one of the treatment options for lamivudine-resistant hepatitis B (HBV) patients in Asia. This study examined the outcome of patients with different baseline resistance genotypes in a cohort study. In this study, 14 patients with chronic HBV were treated with entecavir 1 mg/day for 5 years.

View Article and Find Full Text PDF

Aim: This is a preliminary study to identify older people service needs in Hong Kong from the users' and service providers' perspective.

Background: As the Hong Kong population is ageing rapidly, it is important to identify the needs for care of older people. Although a wide variety of medical and social services have been provided to meet the needs of older people, there has been little evaluation from the users' or service providers' perspective regarding what the needs are and how well current service provisions match their needs.

View Article and Find Full Text PDF