Background: s/Aims: Plasma pregenomic hepatitis B virus RNA (pgRNA) is a novel biomarker in chronic hepatitis B infection (CHB). We aimed to describe the longitudinal profile of pgRNA and factors influencing its levels in CHB patients on nucleoside analogue (NUC). Methods: Serial plasma samples from 1,354 CHB patients started on first-line NUC were evaluated. Time of NUC initiation was taken as baseline (year 0), followed by 1-year, 3-year and 5-year of NUC therapy. pgRNA was measured by Research Use Only RealTime HBV RNA v2.0 (0.2 mL) (Abbott Diagnostics) with lower limit of detection of 0.8 log U/mL (~20 copies/mL). Results: Among 1,354 subjects (median age at baseline 49.8 [interquartile range, IQR 40.2–57.3]) years, 65.2% male, 16.1% hepatitis B e antigen (HBeAg)-positive, 28.6% cirrhotic), baseline median HBV RNA was 3.68 (IQR 2.42–5.19) log U/mL. Upon NUC therapy, median pgRNA levels were 2.45 (IQR 1.82–3.62), 2.23 (IQR 1.67–3.05) and 2.14 (IQR 1.48–2.86) log U/mL at 1, 3 and 5 years, respectively, with the corresponding log U/mL reductions of 0.82, 1.20 and 1.54. Undetectable/ unquantifiable pgRNA was achieved in 13.5%, 15.9% and 20.1% of patients at 1, 3 and 5 years, respectively. Older age, male sex, HBeAg-negativity and high PAGE-B score were associated with lower pgRNA. Conclusions Plasma pgRNA declines are modest under NUC therapy, with only 16.3% achieving RNA undetectability after 5 years of first-line NUC indicating cccDNA silencing has not been achieved in the majority of patients. Clinical characteristics should be taken into consideration when interpreting the plasma pgRNA level.

Background: s/Aims: Plasma pregenomic hepatitis B virus RNA (pgRNA) is a novel biomarker in chronic hepatitis B infection (CHB). We aimed to describe the longitudinal profile of pgRNA and factors influencing its levels in CHB patients on nucleoside analogue (NUC). Methods: Serial plasma samples from 1,354 CHB patients started on first-line NUC were evaluated. Time of NUC initiation was taken as baseline (year 0), followed by 1-year, 3-year and 5-year of NUC therapy. pgRNA was measured by Research Use Only RealTime HBV RNA v2.0 (0.2 mL) (Abbott Diagnostics) with lower limit of detection of 0.8 log U/mL (~20 copies/mL). Results: Among 1,354 subjects (median age at baseline 49.8 [interquartile range, IQR 40.2–57.3]) years, 65.2% male, 16.1% hepatitis B e antigen (HBeAg)-positive, 28.6% cirrhotic), baseline median HBV RNA was 3.68 (IQR 2.42–5.19) log U/mL. Upon NUC therapy, median pgRNA levels were 2.45 (IQR 1.82–3.62), 2.23 (IQR 1.67–3.05) and 2.14 (IQR 1.48–2.86) log U/mL at 1, 3 and 5 years, respectively, with the corresponding log U/mL reductions of 0.82, 1.20 and 1.54. Undetectable/ unquantifiable pgRNA was achieved in 13.5%, 15.9% and 20.1% of patients at 1, 3 and 5 years, respectively. Older age, male sex, HBeAg-negativity and high PAGE-B score were associated with lower pgRNA. Conclusions Plasma pgRNA declines are modest under NUC therapy, with only 16.3% achieving RNA undetectability after 5 years of first-line NUC indicating cccDNA silencing has not been achieved in the majority of patients. Clinical characteristics should be taken into consideration when interpreting the plasma pgRNA level.

Objective: Patients with severe symptomatic aortic stenosis are assessed for coronary artery disease (CAD) prior to transcatheter aortic valve implantation (TAVI) with treatment implications. Invasive coronary angiography (ICA) is the recommended modality but is associated with peri-procedural complications. Integrating machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) into existing TAVI-planning CT protocol may aid exclusion of significant CAD and thus avoiding ICA in selected patients. Materials and Methods: A single-center, retrospective study was conducted, 41 TAVI candidates with both TAVI-planning CT and ICA performed were analyzed. CT datasets were evaluated by a ML-based CT-FFR software. Beta-blocker and nitroglycerin were not administered in these patients. The primary outcome was to identify significant CAD. The diagnostic performance of CT-FFR was compared against ICA. Results: On per-patient level, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were 89%, 94%, 80%, 97% and 93%, respectively. On per-vessel level, the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 75%, 94%, 67%, 96% and 92%, respectively. The area under the receiver operative characteristics curve per individual coronary vessels yielded overall 0.90 (95% confidence interval 85%–95%). ICA may be avoided in up to 80% of patients if CT-FFR results were negative. Conclusion ML-based CT-FFR can provide accurate screening capabilities for significant CAD thus avoiding ICA. Its integration to existing TAVI-planning CT is feasible with the potential of improving the safety and efficiency of pre-TAVI CAD assessment.

Background: s/Aims: Plasma pregenomic hepatitis B virus RNA (pgRNA) is a novel biomarker in chronic hepatitis B infection (CHB). We aimed to describe the longitudinal profile of pgRNA and factors influencing its levels in CHB patients on nucleoside analogue (NUC). Methods: Serial plasma samples from 1,354 CHB patients started on first-line NUC were evaluated. Time of NUC initiation was taken as baseline (year 0), followed by 1-year, 3-year and 5-year of NUC therapy. pgRNA was measured by Research Use Only RealTime HBV RNA v2.0 (0.2 mL) (Abbott Diagnostics) with lower limit of detection of 0.8 log U/mL (~20 copies/mL). Results: Among 1,354 subjects (median age at baseline 49.8 [interquartile range, IQR 40.2–57.3]) years, 65.2% male, 16.1% hepatitis B e antigen (HBeAg)-positive, 28.6% cirrhotic), baseline median HBV RNA was 3.68 (IQR 2.42–5.19) log U/mL. Upon NUC therapy, median pgRNA levels were 2.45 (IQR 1.82–3.62), 2.23 (IQR 1.67–3.05) and 2.14 (IQR 1.48–2.86) log U/mL at 1, 3 and 5 years, respectively, with the corresponding log U/mL reductions of 0.82, 1.20 and 1.54. Undetectable/ unquantifiable pgRNA was achieved in 13.5%, 15.9% and 20.1% of patients at 1, 3 and 5 years, respectively. Older age, male sex, HBeAg-negativity and high PAGE-B score were associated with lower pgRNA. Conclusions Plasma pgRNA declines are modest under NUC therapy, with only 16.3% achieving RNA undetectability after 5 years of first-line NUC indicating cccDNA silencing has not been achieved in the majority of patients. Clinical characteristics should be taken into consideration when interpreting the plasma pgRNA level.

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

Juvenile polyps (JPs) are the most common polyps in pediatric patients. We present the case of an 18-year-old male patient with a giant solitary JP resembling solitary rectal ulcer syndrome (SRUS). The presenting history was rectal bleeding and symptoms of obstructed defecation syndrome. Colonoscopy revealed a polypoidal mass at the anorectal junction, with biopsy-confirmed SRUS. The symptoms worsened, and a protruding mass from the anus caused fecal incontinence. Pelvic magnetic resonance imaging showed a huge pedunculated mass occupying the low rectum with local compression of the urinary bladder. Transanal excision of the anal tumor was performed due to bleeding. A histopathological examination showed a JP with high-grade dysplasia. A histological examination to differentiate JPs and SRUS could be challenging based on a superficial forceps biopsy. Therefore, an excision biopsy is usually warranted with the understanding that adenomatous or malignant transformation is found in 5.6% to 12% of all JPs.

FACTORS ASSOCIATED WITH PAROXYSMAL VERTIGO AMONG URBAN-DWELLERS AGED 55 YEARS AND OVER IN THE MALAYSIAN ELDERS LONGITUDINAL RESEARCH (MELOR) STUDY Background: Paroxysmal Vertigo (PV) negatively affects life quality and increases in prevalence with age, but the risk factors remain inconclusive. Objective: The present study aimed to investigate the risk factors of PV among a multi-ethnic urban population in late mid-life and late life within a middle-income Southeast-Asian country. Methods: Cross-sectional data from the first wave of the Malaysian Elders Longitudinal Research (MELoR) study were utilized for this study involving randomly sampled participants aged 55 years and over. Socio-demographics, comorbidities, and psychological status were obtained through home-based computer-assisted interviews. Results: Based on an analysis of 1530 participants, mean age (SD) = 68.81 (7.49), 64.9% female; 32.9% Malay, 34.6% Chinese), the lifetime prevalence of PV was 12.1%. The risk factors associated based on multivariate analysis were hypertension, osteoarthritis, depression, and vitamin B12 Deficiency. Chinese ethnicity (OR = 0.582; 95% CI = 0.390 to 0.870) and smoking (OR = 0.377; 95% CI = 0.223 to 0.637) were protective factors against PV. Conclusions: While the risk factors reported are similar to other studies, the lower prevalence of PV among ethnic Chinese and smokers had not previously been reported. Our study highlighted potential genetic and lifestyle links to PV which should be evaluated in future studies.

A 61-year-old gentleman presented with small bowel intussusception from small bowel melanoma intussusceptum. He complains of intermittent abdominal distension but no history of intestinal obstruction. Apart from this, he was also symptomatic anemia which required repeated transfusion for the past few months. The contrast-enhanced computed tomography of the abdomen shows an omental mass with small bowel intussusception. He then underwent an exploratory laparotomy with segmental resection of the affected segment. Histopathological examination confirmed primary gastrointestinal melanoma. Multiple small bowel malignant melanoma is a rare disease. It remains a controversial diagnosis as it may be a primary or metastasis from an unidentified or regressed primary cutaneous melanoma. Prompt surgical intervention enables us to obtain tissue diagnosis, prevent complete intestinal obstruction and strategize the goals of treatment for the patient.

Aims: Recent discoveries have revealed that Glaciozyma antarctica PI12 has been discovered to encode numerous protein-coding genes that are crucial for thermal adaptation. However, more than 35% of the protein-coding genes for this species were identified as hypothetical proteins (HP). Nevertheless, over 35% of the protein-coding genes for this species were classified as hypothetical proteins (HP). Previous studies have documented the role of these uncharacterized proteins in the physiological regulation and cold adaptation of psychrophilic microorganisms. Thus, we aim to identify the structural features of the conserved HPs that were ideal for their function in response to temperature stress. Methodology and results: Three conserved HPs of G. antarctica, designated GaHP2, GaHP3 and GaHP4, were cloned, expressed purified and their function and structure were evaluated. Functional analysis showed that these proteins maintained their activities at low temperatures below 25 °C, but at a lower reaction rate. Meanwhile, thermal unfolding assays revealed the stability of GaHP2 and GaHP4 at high temperatures (43 °C), suggesting their non-ATPbinding chaperone activity. The comparative structural analysis demonstrated that the HPs exhibited cold-adapted traits, most notably increased flexibility in their 3D structures. For GaHP2, the aromatic residues can be linked to its heat stability. GaHP4's cold shock domain implies it regulates gene transcription and translation during temperature fluctuations. Conclusion, significance and impact of study: This study has established the structure-function relationships of the G. antarctica HPs and provided fundamental experimental data highlighting their importance in thermal stress response by maintaining a balance between molecular stability and structural flexibility.

Aims: The search for new antibiotics is an ongoing effort and has expanded to pristine niche areas in the Antarctic in recent years due to the emergence of multi-drug resistant pathogens that outpaced the discovery of new antibiotics. We have recently isolated two new actinomycetes strains, INACH3013a and INACH3013b, which displayed antimicrobial properties from soil samples collected from Ardley Island, Antarctica. Hence, an investigation was carried out to identify them and to characterise the antimicrobial compounds produced. Methodology and results: Strains, INACH3013a and INACH3013b were identified based on their 16S rDNA sequence alignment to those in the GenBank. The results showed that strain INACH3013a was closest to Streptomyces spp. while strain INACH3013b was closest to Streptomyces corallincola and Streptomyces bullii. The extracellular compounds they produced were extracted using various solvents and the extracted compounds were tested against the test pathogens. The dichloromethane extracts from strains, INACH3013a and INACH3013b inhibited mainly Gram-positive pathogens that include Listeria monocytogenes, Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus equorum, Bacillus cereus K3 and Enterococcus faecalis while extracts from strain INACH3013b also inhibited a Gram-negative pathogen, Klebsiella pneumonia 14x. Predominantly non-polar constituents seem responsible for antibacterial effects, with dichloromethane extracts proving most efficacious, followed by chloroform and ethyl acetate. Conclusion, significance and impact of study The research highlights the potential of Streptomyces spp. INACH3013a and INACH3013b as a source of potential novel antibiotics. This research explores Antarctic Streptomyces strains' antimicrobial capabilities, enabling the potential for the discovery of novel antibiotics and revealing how these compounds may have helped them to compete and survive in nutrient-deficient Antarctic niches.