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Abstract Background Half of patients with heart failure are estimated to have sleep‐disordered breathing (SDB). However, many are undiagnosed as they do not report typical symptoms. This study aims to evaluate the implantable cardiac defibrillator (ICD) sleep‐disordered breathing algorithm in a cohort of multi‐racial Asian patients for detection of SDB against polysomnography (PSG). Methods In this prospective pilot study, participants who fulfill the American College of Cardiology (ACC) indication for ICD were recruited. The ICD algorithm uses transthoracic impedance sensing to calculate respiratory disturbance index (RDI). Results Twenty‐four patients were enrolled between August 2020 and December 2021. All patients underwent PSG exams and were followed up for up to 12 months. Eighteen participants completed the PSG study as of August 23, 2022. Severe SDB (defined as PSG‐AHI ≥30 episodes/h) was diagnosed in 66.7% of the patients. No significant direct linear correlation was found between the PSG‐AHI measurements and the RDI measurements (adjusted r2 = .224, r = .473, p = .027). Applying a binary threshold cut‐off RDI value of 32 episodes/h for the detection of severe SDB yielded a sensitivity of 91.7% and specificity of 16.7%. Conclusions Transthoracic impedance sensing with an advanced inbuilt algorithm may be helpful as a screening test in detecting severe SDB in patients with heart failure and cardiomyopathy, potentially by applying a binary threshold cut‐off value. This is the first study known to validate the algorithm in an exclusively multi‐ethnic Asian population with heart failure.

Objective: To elucidate the characteristics, management strategies, risk factors, and clinical impacts associated with adverse drug reactions (ADRs) induced by first-line antitubercular drugs to enhance tuberculosis (TB) management. Methods: A retrospective cohort study was conducted by retrieving drug-susceptible TB records among adult patients who received TB treatment from 2018 to 2021 at 10 public health clinics in Sarawak, Malaysia. Only the initial TB treatment and occurrence of specific ADRs within the study period were considered. Regression analysis was performed to identify the risk factors associated with both overall ADRs and individual types of ADRs. Results: Among 2 953 cases, 705 (23.9%) developed ADRs. Cutaneous reactions were the most prevalent (47.1%), followed by hepatotoxicity (32.8%) and gastrointestinal disturbances (29.8%). Six out of seven types of ADRs investigated occurred within the intensive phase, mostly manifesting at approximately 2 weeks of initiation. Hepatotoxicity resulted in the majority (85.3%) of treatment discontinuations, while vision problems led to treatment modifications in half of the cases. Risk factors for all ADRs included age ≥60 years, females, illicit drug use, and comorbidities such as HIV-positive, diabetes, and chronic liver disease. Alcohol consumption was independently associated with hepatotoxicity. ADRs caused around one-third of interruptions exceeding 2 weeks (33.0%) and subsequently necessitated treatment restarts (34.5%). Conclusions: Understanding these various aspects contributes to improving the overall management of ADRs in TB treatment. Close ADR monitoring and reporting are essential to strengthen ADR management.

Abstract Molybdenum sulfide (MoS2) and modified MoS2 with different percentages of CdS (10%, 30%, and 50% CdS@MoS2) were successfully synthesized and characterized. The photocatalytic performance of the MoS2 and CdS@MoS2 was evaluated by degrading brilliant green (BG), methylene blue (MB), and rhodamine B (RhB) dyes under visible light irradiation. Amongst the synthesized photocatalysts, 50% CdS@MoS2 exhibited the highest photocatalytic activity, degrading 97.6%, 90.3%, and 75.5% of BG, MB, and RhB dyes, respectively within 5 h. The active species involved in the degradation processes were investigated. All trapping agents inhibited BG and MB degradation to a similar extent, indicating that all of the probed active species play an important role in the degradation of BG and MB. In contrast, h+ and O2 •− were found to be the main reactive species in the photocatalytic RhB degradation. A potential mechanism for the photocatalytic degradation of dyes using CdS@MoS2 has been proposed. This work highlights the potential of CdS@MoS2 as a photocatalyst for more efficient water remediation applications.

BackgroundWhile perceptions of electronic labeling (e-labeling) in developed countries have been generally positive, existing data primarily come from studies involving hospital pharmacists, community pharmacy customers who may not be frequent medication users, and individuals receiving COVID-19 vaccines. ObjectiveThis study aims to assess e-labeling acceptance, perceptions of its benefits, challenges with its implementation, and preferences among hospital ambulatory care patients in Malaysia. Additionally, the study investigates the factors influencing patients’ acceptance of e-labeling. MethodsA cross-sectional study using a 28-item questionnaire was conducted at the outpatient pharmacy department of a quaternary hospital in Kuala Lumpur, Malaysia, from May to June 2023. The questionnaire was developed based on a review of published literature related to e-labeling and was guided by the Unified Theory of Acceptance and Use of Technology, second version (UTAUT2). Patients aged 18 years and above were recruited using a stratified sampling method to ensure representative age-related medication usage. A mobile tablet was provided to patients for self-completion of the e-survey in their preferred language (English, Malay, or Mandarin). Categorical data on e-labeling acceptance, perceptions, and preferences were analyzed using descriptive statistics. Qualitative content analysis was performed to characterize participants’ responses to open-ended questions. Univariate and multivariate binomial logistic regression analyses were conducted to identify predictors of e-labeling acceptance. ResultsOut of 462 patients approached, 387 (83.8%) participated in the survey, with 283 (73.1%) accepting e-labeling. Most participants perceived the electronic version of the package insert as beneficial, particularly for understanding their medication better through the choice of language (352/387, 91.0%). However, around half of the participants (197/387, 50.9%) expressed concerns about the potential risks of obtaining illegal medication information via e-labeling. Most participants (302/387, 78.0%) preferred to access electronic leaflets through government websites. However, 221/387 (57.1%) still wanted the option to request printed leaflets. Significant predictors of e-labeling acceptance included perceived benefits such as better understanding of medication (adjusted odds ratio [AOR] 8.02, 95% CI 2.80-22.97, P

Abstract Background Pneumothorax can cause distressing breathlessness, however the effect of the accumulated air in the pleural space and its association with diaphragmatic function and symptoms of breathlessness is not well understood. Bendopnoea is an evolving clinical symptom that has been demonstrated as clinically useful in some heart and lung conditions. Whether bendopnoea is present in patients with pneumothorax, and its potential clinical usefulness has not yet been investigated. The PASE study is a pilot study to explore the incidence and clinical relevance of bendopnoea in patients with pneumothorax and may provide better understanding of pneumothorax related dyspnoea. Methods PASE is a prospective study. Eligible patients are assessed at baseline (pre air drainage/lung reinflation) and in patients whose pneumothorax resolves once the lung has re‐expanded (post conservative management or air drainage procedure). Outcome measures include the incidence of bendopnoea, correlation of the associated symptoms (pain and breathlessness) to the severity of bendopnoea and the size of pneumothorax; and correlation with clinical outcome (i.e., response to air drainage/lung reinflation). The study will recruit 50 participants. Discussion This is the first study to explore bendopnoea in patients with pneumothorax. The presence and significance of bendopnoea in relation to clinical and physiological parameters in patients with pneumothorax requires investigation. The findings of this study may further current understanding of dyspnoea related pneumothorax. Trial Registration Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number: ACTRN12623001109695p. URL of the trial registry record for this trial: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386631&isReview=true Date of registration: Registered on 24 October 2023. Funding of the trial: This study has not received grant support. The study is sponsored by the Institute for Respiratory Health, a not‐for‐profit organisation. Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands, WA 6009. Role of sponsor: The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript. Protocol version: 1.

Abstract Background Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. Methods A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. Discussion Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. Ethics and dissemination Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Abstract Background Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a ‘trial and error’ basis, as symptom relief varies. This population commonly complain of bendopnoea (breathlessness on bending forward) which has not been investigated. Our pilot data found bendopnoea was significantly associated with presence of pleural effusion. The PLEASE‐3 study will evaluate bendopnoea as a screening test for effusion‐related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore its underlying physiological mechanism. Methods PLEASE‐3 is a multi‐centre prospective study. Eligible patients are assessed at baseline (pre‐drainage) and for patients undergoing drainage, up to 72 h post‐procedure. Outcome measures include the prevalence of bendopnoea, its correlation with size of effusion and its predictive value of breathlessness relief after drainage. The relationship of bendopnoea with breathlessness, physiological parameters, functional capacity and diaphragmatic characteristics will be assessed. The study will recruit 200 participants. Discussion This is the first study to investigate bendopnoea in patients with pleural effusion. It has minimal exclusion criteria to ensure that the results are generalisable. The presence and clinical significance of bendopnoea in the context of pleural effusion requires thorough investigation. The post assessment of patients undergoing pleural fluid drainage will provide insight into whether the presence of bendopnoea is able to predict clinical outcomes. Trial Registration Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number: ACTRN12622000465752. URL of the trial registry record for this trial: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383639&isReview=true Date of registration: Registered on 24 March 2022. Funding of the trial: This study has received funding from the Sir Charles Gairdner Research Advisory Council research project grant. The study is sponsored by the Institute for Respiratory Health, a not‐for‐profit organisation. Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands WA 6009. t‖ + 61 8 6151 0877 e‖ bi.lam@resphealth.uwa.edu.au Role of sponsor: The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.

Polypropylene is extensively used in aerospace, automotive and construction applications due to its versatile properties. This project aims to reduce plastic and oil palm waste and promote the development of strong, sustainable and eco-friendly construction materials. The objective of this project is to develop a sustainable yet high-performance construction material by incorporating polypropylene particles, oil palm empty fruit bunch (OPEFB) fibres and oil palm shell (OPS) particles into epoxy composites through the hand lay-up method. The composite specimens undergo ASTM D638 tensile test to determine the tensile properties. The addition of PP particles in varying weights shows decrease in tensile strength, likely due to poor dispersion and compatibility with the epoxy matrix. Incorporating 3 wt% OPEFB fibres with fibre length from 2mm to 4mm improves tensile strength by 2.32% and 23.36% respectively at higher PP particle loadings which are 15 wt% and 25 wt%. Adding 1 wt% and 3 wt% OPS particles improves the tensile strength by 2.96% and 4.68% respectively, in composites with 10 wt% PP particles and 3 wt% OPEFB fibres. The tensile performance may be improved by treating PP particles with compatibilizers such as silane or maleic anhydride grafted polypropylene.

IntroductionPharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related to CYP2D6 in children from the GUSTO cohort.MethodsBuffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated with CYP2D6 were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of the CYP2D6 gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models’ performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites.ResultsOverall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model.DiscussionThe development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing.

Phosphorus (P) deficiency is a predominant constraint on plant growth in acidified soils, largely due to the sequestration of P by toxic aluminum (Al) compounds. Indigenous phosphorus-solubilizing bacteria (PSBs) capable of mobilizing Al-P in these soils hold significant promise. A novel Al-P-solubilizing strain, Al-P Nguyenibacter sp. L1, was isolated from the rhizosphere soil of healthy Lespedeza bicolor plants indigenous to acidic terrains. However, our understanding of the genomic landscape of bacterial species within the genus Nguyenibacter remains in its infancy. To further explore its biotechnological potentialities, we sequenced the complete genome of this strain, employing an amalgamation of Oxford Nanopore ONT and Illumina sequencing platforms. The resultant genomic sequence of Nguyenibacter sp. L1 manifests as a singular, circular chromosome encompassing 4,294,433 nucleotides and displaying a GC content of 66.73%. The genome was found to host 3,820 protein-coding sequences, 12 rRNAs, and 55 tRNAs. Intriguingly, annotations derived from the eggNOG and KEGG databases indicate the presence of genes affiliated with phosphorus solubilization and nitrogen fixation, including iscU, glnA, and gltB/D associated with nitrogen fixation, and pqqBC associated with inorganic phosphate dissolution. Several bioactive secondary metabolite genes in the genome, including pqqCDE, phytoene synthase and squalene synthase predicted by antiSMASH. Moreover, we uncovered a complete metabolic pathway for ammonia, suggesting an ammonia-affinity property inherent to Nguyenibacter sp. L1. This study verifies the nitrogen-fixing and phosphate-dissolving abilities of Nguyenibacter sp. L1 at the molecular level through genetic screening and analysis. The insights gleaned from this study offer strategic guidance for future strain enhancement and establish a strong foundation for the potential incorporation of this bacterium into agricultural practices.

IntroductionThis scoping review focuses on the eating behaviour of Malaysian youths and the way in which their eating behaviour has been studied in recent years. There is a continuous need to comprehend the nature and structure of eating behaviour acquired during young adulthood as it is linked to the increasing number of adults who are overweight and obese. Past research has been employed using various methodologies in the analysis of different dimensions of eating behaviour amongst Malaysian youths. This enquiry reviewed recent studies to collate and map out the methodologies, areas of research and factors associated with eating behaviour amongst this target group.MethodsThe “preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews” (PRISMA-ScR) was adopted for this scoping review which utilised the EBSCOhost discovery platform and other such databases as Sage, ProQuest and Clinical Key™.ResultsThe search resulted in a total of 34 articles which were then analysed. This gave rise to the identification of four main dimensions of eating behaviour amongst Malaysian youth, namely: “general adequacy and frequency of consumption of food groups”; “consumption of specific food groups”; “eating disorders”; and “weight control.”ConclusionThe majority of the recent studies focused on the general adequacy and frequency of consumption of food groups studied using quantitative approaches across multi-ethnic target groups within the central region of Malaysia. This leaves room for more studies on the consumption of specific food groups, eating disorders and weight control that could be more ethnic-centric within other geographical areas within Malaysia. Many studies suggested the need to apply qualitative measures to investigate the contradictions arising from current research concerning the interplay between interpersonal, intrapersonal and environmental factors affecting eating behaviour amongst Malaysian youths.

We report a case of intractable Aspergillus otomycosis with multiple relapses despite conventional topical and systemic antifungal treatment, and adjunctive usage of hyperbaric oxygen therapy. Of note, otomycosis relapsed even after six months of continuous systemic antifungal treatment with therapeutic drug levels and without treatment interruption; and only resolved after application of topical voriconazole. (max. 75 words)

Abstract Introduction Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. Methods and analysis A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. Ethics and dissemination Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. Discussion Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018. Protocol version: Version 3.00/4.02.19

This research examines the rise of a new religious travel segment – the Umrah Do It Yourself (DIY) travellers. While Hajj is the fifth pillar of Islam, Umrah is a minor Muslim pilgrimage that can be undertaken at any time of the year, while still playing a crucial role in the completion of Hajj rituals. In the past, Umrah was managed by an authorised travel agent, who makes all the necessary pilgrimage preparations, from flights to trip itineraries. Recent years have seen an upsurge in travellers who prefer not to utilise the services of such agencies, but instead, to make their own arrangements. The decision by the Saudi Arabian government to launch a Tourist e-Visa in September 2019 has opened a window of opportunity for the legalization of Umrah DIY journeys. The objectives of this study are (i) to explore the travel motives that contribute to the success of the Umrah DIY, and (ii) to explore the factors that support and facilitate the decision for the Umrah DIY. The data were obtained via 20 semi-structured interviews with Umrah DIY travellers. The findings show that flexibility, spirituality, and budget have a crucial impact on travel motivation. Additionally, the findings suggest that information sources, travel quality, companionship/new friendship, and familiarity facilitate the choice of Umrah DIY travel. This research contributes to the growing scholarship on the Muslim travel market beyond Hajj and to studies on independent religious travel. Findings provide an opportunity for suppliers and industry participants to understand the travel motives of this new segment as a basis for producing relevant religious tourism products and services.

Introduction Tuberculosis (TB) treatment interruption remains a critical challenge leading to poor treatment outcomes. Two-thirds of global new TB cases are mostly contributed by Asian countries, prompting systematic analysis of predictors for treatment interruption due to the variable findings.Methods Articles published from 2012 to 2021 were searched through seven databases. Studies that established the relationship for risk factors of TB treatment interruption among adult Asian were included. Relevant articles were screened, extracted and appraised using Joanna Briggs Institute’s checklists for cohort, case–control and cross-sectional study designs by three reviewers. Meta-analysis was performed using the random effect model in Review Manager software. The pooled prevalence and predictors of treatment interruption were expressed in ORs with 95% CIs; heterogeneity was assessed using the I2 statistic. The publication bias was visually inspected using the funnel plot.Results Fifty eligible studies (658 304 participants) from 17 Asian countries were included. The overall pooled prevalence of treatment interruption was 17% (95% CI 16% to 18%), the highest in Southern Asia (22% (95% CI 16% to 29%)), followed by Eastern Asia (18% (95% CI 16% to 20%)) and South East Asia (16% (95% CI 4% to 28%)). Seven predictors were identified to increase the risk of treatment interruption, namely, male gender (OR 1.38 (95% CI 1.26 to 1.51)), employment (OR 1.43 (95% CI 1.11 to 1.84)), alcohol intake (OR 2.24 (95% CI 1.58 to 3.18)), smoking (OR 2.74 (95% CI 1.98 to 3.78)), HIV-positive (OR 1.50 (95% CI 1.15 to 1.96)), adverse drug reactions (OR 2.01 (95% CI 1.20 to 3.34)) and previously treated cases (OR 1.77 (95% CI 1.39 to 2.26)). All predictors demonstrated substantial heterogeneity except employment and HIV status with no publication bias.Conclusion The identification of predictors for TB treatment interruption enables strategised planning and collective intervention to be targeted at the high-risk groups to strengthen TB care and control in the Asia region.

Background Delays in producing discharge prescriptions have hindered the provision of bedside dispensing services (BEDISC) that enable medication reconciliation and pharmaceutical intervention, which is an important element in transitional care medication safety. We aimed to assess the impact of early medication discharge planning on the delivery of BEDISC in terms of the rate of bedside dispensing, medication errors, and cost-saving from medication reconciliation by reusing patient’s own medicines (POMs). Methods A pre–post intervention study was conducted at medical wards in a public tertiary hospital. During the intervention phase, a structured bedside dispensing process was delineated and conveyed to the doctors, nurses, and pharmacists. Regular verbal reminders were given to the doctors to prioritize discharge patients by producing the prescriptions once discharge decisions had been made and nurses to hand the prescriptions to ward pharmacists and not patients. Throughout the study, ward pharmacists were involved in medication reconciliation via screening of discharge prescriptions and reusing POMs, performed pharmaceutical interventions for any medication errors detected, and provided bedside dispensing with discharge counseling. Comparisons were made between bedside versus counter-dispensing at pre–post intervention phases using the chi-square test. Results A total of 1097 and 817 discharge prescriptions were dispensed in the pre-intervention and post-intervention phases, respectively. The bedside dispensing rate increased by 13.5% following remedial actions (p

Shwachman-Diamond syndrome (SDS) is a leukemia predisposition disorder that is caused by defective release of eIF6 during ribosome assembly. Here the authors show that acquired somatic EIF6 mutations are frequent in the hematopoietic cells from individuals with SDS and provide a selective advantage over non-modified cells.

Summary: Prenatal maternal mental health is a global health challenge with poorly defined biological mechanisms. We used maternal blood samples collected during the second trimester from a Singaporean longitudinal birth cohort study to examine the association between inter-individual genome-wide DNA methylation and prenatal maternal depressive symptoms. We found that (1) the maternal methylome was significantly associated with prenatal maternal depressive symptoms only in mothers with a female fetus; and (2) this sex-dependent association was observed in a comparable, UK-based birth cohort study. Qualitative analyses showed fetal sex-specific differences in genomic features of depression-related CpGs and genes mapped from these CpGs in mothers with female fetuses implicated in a depression-associated WNT/β-catenin signaling pathway. These same genes also showed enriched expression in brain regions linked to major depressive disorder. We also found similar female-specific associations with fetal-facing placenta methylome. Our fetal sex-specific findings provide evidence for maternal-fetal interactions as a mechanism for intergenerational transmission.

Stingless bee honey (SBH) is a natural, sweet product produced by stingless bees (Meliponini tribe) that has been used as a traditional medicine to treat various illnesses. It has been shown that SBH has high nutritional value and health-promoting properties due to the presence of plant bioactive compounds from different botanical flora of the foraged nectar. In this study, the antioxidant activities of seven monofloral honeys from acacia, agarwood, coconut, dwarf mountain pine (DMP), Mexican creeper (MC), rubber, and starfruit botanical origins were investigated. The antioxidant properties of SBH studied had a range from 19.7 to 31.4 mM TE/mg for DPPH assays, 16.1 to 29.9 mM TE/mg for ABTS assays, 69.0 to 167.6 mM TE/mg for ORAC assays, and 45.5 to 89.3 mM Fe2+/mg for FRAP assays. Acacia honey showed the highest level of antioxidant properties. The models built from mass spectral fingerprints from direct ambient mass spectrometry showed distinct clusters of SBH by botanical origin and correlated with the antioxidant properties. An untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach was undertaken to identify the antioxidant compounds that could explain the unique antioxidant and compositional profiles of the monofloral SBH by its botanical origin. The antioxidants that were identified predominantly consisted of alkaloids and flavonoids. Flavonoid derivatives, which are potent antioxidants, were found to be key markers of acacia honey. This work provides the fundamental basis for the identification of potential antioxidant markers in SBH associated with the botanical origin of the foraged nectar.

We report a novel case of a full term newborn with non-immune fetal hydrops and arterial tortuosity mimicking a double aortic arch, and cranial fractures in the immediate neonatal period. The infant had no classic features of neonatal arterial tortuosity syndrome or Loeys Dietz syndrome apart from bilateral inguinal hernia. He also had skeletal manifestations in the form of fractures in the neonatal period without any trauma during birth and without clinical evidence of Osteogenesis Imperfecta. A heterozygous missense variant of uncertain significance was detected in MYH11 gene which is increasingly recognized to be belonging to the familial/hereditary thoracic aneurysm and aortic dissection group of disorders. Fetal hydrops as an association with arterial tortuosity has not been reported in the literature. We hypothesize the possible mechanism behind developing fetal hydrops in this case and discuss the genetic and phenotypic heterogeneity of the Familial Thoracic Aortic Aneurysm and Dissection (FTAAD) group of conditions highlighting the unique phenotypic and genotypic presentations. We recommend a high index of suspicion and vigilance in the early detection of such potentially lethal conditions with sequelae also in adulthood.

Background: Autonomous vehicles are important in smart transportation. Although exciting progress has been made, it remains challenging to design a safety mechanism for autonomous vehicles despite uncertainties and obstacles that occur dynamically on the road. Collision detection and avoidance are indispensable for a reliable decision-making module in autonomous driving. Methods: This study presents a robust approach for forward collision warning using vision data for autonomous vehicles on Malaysian public roads. The proposed architecture combines environment perception and lane localization to define a safe driving region for the ego vehicle. If potential risks are detected in the safe driving region, a warning will be triggered. The early warning is important to help avoid rear-end collision. Besides, an adaptive lane localization method that considers geometrical structure of the road is presented to deal with different road types. Results: Precision scores of mean average precision (mAP) 0.5, mAP 0.95 and recall of 0.14, 0.06979 and 0.6356 were found in this study. Conclusions: Experimental results have validated the effectiveness of the proposed approach under different lighting and environmental conditions.

Background: The unprecedented development of Artificial Intelligence has revolutionised the healthcare industry. In the next generation of healthcare systems, self-diagnosis will be pivotal to personalised healthcare services. During the COVID-19 pandemic, new screening and diagnostic approaches like mobile health are well-positioned to reduce disease spread and overcome geographical barriers. This paper presents a non-invasive screening approach to predict the health of a person from visually observable features using machine learning techniques. Images like face and skin surface of the patients are acquired using camera or mobile devices and analysed to derive clinical reasoning and prediction of the person’s health. Methods: In specific, a two-level classification approach is presented. The proposed hierarchical model chooses a class by training a binary classifier at the node of the hierarchy. Prediction is then made using a set of class-specific reduced feature set. Results: Testing accuracies of 86.87% and 76.84% are reported for the first and second-level classification. Empirical results demonstrate that the proposed approach yields favourable prediction results while greatly reduces the computational time. Conclusions: The study suggests that it is possible to predict the health condition of a person based on his/her face appearance using cost-effective machine learning approaches.

Gluten avoidance is becoming a popular diet trend around the world. In this study, green Saba banana flour (GSBF) was used to produce a gluten-free (GF) steamed cake. The effects of soy protein isolate (SPI) (0%, 10%, 15%) and Ovalette (0%, 3.5%, 7%) on the quality of the cake were investigated. Physicochemical properties of the flours were measured. The viscosity and specific gravity of the batters; as well as the specific volume, weight loss and texture profile of the resulting cakes were determined. Sensory evaluation was performed to compare the acceptance of the cake formulations. The macronutrient and resistant starch content of the cakes were determined. The use of an appropriate level of SPI and Ovalette was found to effectively enhance the aeration of the cake batter and improved the specific volume and weight loss of the cake. The presence of Ovalette was essential to soften the texture of the cake. GF cake supplemented with 10% SPI and 3.5% Ovalette obtained the highest sensorial acceptance. The nutritional quality of this sample was significantly improved, whereby it contained higher protein than the gluten-containing counterpart. GSBF also contributed to the high dietary fiber and resistant starch content of the cake.

Candida infections of the central nervous system (CNS) are rare. We report a case of Candida glabrata meningitis successfully treated with combination antifungal therapy followed by step-down therapy with fluconazole. New-onset hypercalcaemia, an uncommon side effect of the prolonged fluconazole treatment, prompted early treatment cessation. A negative cerebrospinal fluid (CSF) β-d-glucan supported the decision of treatment cessation despite incomplete resolution of CSF biochemical parameters. No disease relapse was encountered after 2 years post-treatment.

Abstract Background CHILD syndrome is an X‐linked dominant disorder associated with pathogenic mutations in the NSDHL gene. The condition is predominantly found in females as it is lethal in males. Most cases present at birth with extensive unilateral ichthyosiform erythroderma involving the trunk and limbs. Milder and less extensive presentations have been reported, leading to misdiagnosis especially during early childhood. Methods and Results We report an adult female of Malay ancestry who presented with minimal skin and limb involvement. She was only diagnosed in adulthood when she presented with gastrointestinal symptoms and worsening of skin manifestations. The clinical diagnosis was suspected after a combination of clinical, pathological and immunohistochemistry correlation, and molecularly confirmed with the discovery of a frameshift variant in NSDHL. The novel variant was inherited from her mother who had some linear hypopigmented patches over the medial aspects of both her arms and right forearm. Conclusion We uncovered a novel frameshift variant associated with presentations that cast a new light on the clinical features of CHILD syndrome.

Abstract Background Preterm birth (PTB), defined as child birth before completion of 37 weeks of gestation, is a major challenge in perinatal health care and can bear long-term medical and financial burden. Over a million children die each year due to PTB complications, and those who survive can face developmental delays. Unfortunately, our understanding of the molecular pathways associated with PTB remains limited. There is a growing body of evidence suggesting the role of DNA methylation (DNAm) in mediating the effects of PTB on future health outcomes. Thus, epigenome-wide association studies (EWAS), where DNAm sites are examined for associations with PTB, can help shed light on the biological mechanisms linking the two. Results In an Asian cohort of 1019 infants (68 preterm, 951 full term), we examined and compared the associations between PTB and genome-wide DNAm profiles using both cord tissue (n = 1019) and cord blood (n = 332) samples on Infinium HumanMethylation450 arrays. PTB was significantly associated (P

The increase in health and safety concerns regarding chemical modification in recent years has caused a growing research interest in the modification of starch by physical techniques. There has been a growing trend toward using a combination of treatments in starch modification in producing desirable functional properties to widen the application of a specific starch. In this study, a novel combination of gamma irradiation and annealing (ANN) was used to modify sago starch (Metroxylon sagu). The starch was subjected to gamma irradiation (5, 10, 25, 50 kGy) prior to ANN at 5 °C (To-5) and 10 °C (To-10) below the gelatinization temperature. Determination of amylose content, pH, carboxyl content, FTIR (Fourier Transform Infrared) intensity ratio (R1047/1022), swelling power and solubility, thermal behavior, pasting properties, and morphology were carried out. Annealing irradiated starch at To-5 promoted more crystalline perfection as compared to To-10, particularly when combined with 25 and 50 kGy, whereby a synergistic effect was observed. Dual-modified sago starch exhibited lower swelling power, improved gel firmness, and thermal stability with an intact granular structure. Results suggested the potential of gamma irradiation and annealing to induce some novel characteristics in sago starch for extended applications.

Aim The long-term stress, anxiety and job burnout experienced by healthcare workers (HCWs) are important to consider as the novel coronavirus disease (COVID-19) pandemic stresses healthcare systems globally. The primary objective was to examine the changes in the proportion of HCWs reporting stress, anxiety, and job burnout over six months during the peak of the pandemic in Singapore. The secondary objective was to examine the extent that objective job characteristics, HCW-perceived job factors, and HCW personal resources were associated with stress, anxiety, and job burnout. Method A sample of HCWs (doctors, nurses, allied health professionals, administrative and operations staff; N = 2744) was recruited via invitation to participate in an online survey from four tertiary hospitals. Data were gathered between March-August 2020, which included a 2-month lockdown period. HCWs completed monthly web-based self-reported assessments of stress (Perceived Stress Scale-4), anxiety (Generalized Anxiety Disorder-7), and job burnout (Physician Work Life Scale). Results The majority of the sample consisted of female HCWs (81%) and nurses (60%). Using random-intercept logistic regression models, elevated perceived stress, anxiety and job burnout were reported by 33%, 13%, and 24% of the overall sample at baseline respectively. The proportion of HCWs reporting stress and job burnout increased by approximately 1·0% and 1·2% respectively per month. Anxiety did not significantly increase. Working long hours was associated with higher odds, while teamwork and feeling appreciated at work were associated with lower odds, of stress, anxiety, and job burnout. Conclusions Perceived stress and job burnout showed a mild increase over six months, even after exiting the lockdown. Teamwork and feeling appreciated at work were protective and are targets for developing organizational interventions to mitigate expected poor outcomes among frontline HCWs.

Background: Catheter ablation is increasingly being performed worldwide for atrial fibrillation (AF). However, there are concerns of lower success rates and higher complications of AF ablations performed in low-volume centers. Thus, we sought to evaluate the safety and efficacy of AF catheter ablation in a low-volume center using contemporary technologies. Methods and results: 71 consecutive patients (50 paroxysmal AF [pAF] vs 21 persistent AF) who underwent first catheter ablation were studied. Primary outcome was AF recurrence rate. Secondary outcomes included periprocedural complications, hospitalization for symptomatic tachy-arrhythmias post-ablation and number of repeat ablations. Mean age of our cohort was 59.1 ± 9.7 years, of which 56 (78.9%) were males. 1-year AF recurrence was 19.5% in pAF and 23.8% in persistent AF (p = 0.694). Ablation in persistent AF group required longer procedural (197.76 ± 48.60 min [pAF] vs 238.67 ± 70.50 min [persistent AF], p = 0.006) and ablation duration (35.08 ± 15.84 min [pAF] vs 52.65 ± 28.46 min [persistent AF], p = 0.001). There were no significant differences in secondary outcomes. Major periprocedural complication rate was 2.8%.Subset analysis on (i) cryoablation vs radiofrequency, (ii) Ensite vs CARTO navigational system and (iii) circular vs high density mapping catheter did not yield significant differences in primary or secondary outcomes. Conclusions: The AF ablation complication and recurrence free rates in both paroxysmal and persistent AF at one year were comparable to high-volume centers. Long-term follow up is needed. In addition, first AF catheter ablation in a low-volume center is realistic with comparable efficacy and safety outcomes to high-volume centers using contemporary ablation technologies.

Accounting for cellular heterogeneity is essential in neonatal epigenome-wide association studies (EWAS) performed on heterogeneous tissues, such as umbilical cord tissue (CT) or cord blood (CB). Using a reference-panel-based statistical approach, the cell type composition of heterogeneous tissues can be estimated by comparison of whole tissue DNA methylation profiles with cell type-specific DNA methylation signatures. Currently, there is no adequate DNA methylation reference panel for CT, and existing CB panels have been generated on lower coverage Infinium HumanMethylation450 arrays. In this study, we generate a reference panel for CT and improve available CB panels by using the higher coverage Infinium MethylationEPIC arrays. We performed DNA methylation profiling of 9 cell types isolated from CT and CB samples from 14 neonates. In addition to these cell types, we profiled DNA methylation of unfractionated CT and CB. Cell type composition of these unfractionated tissue samples, as estimated by our reference panels, was in agreement with that obtained by flow cytometry. Expectedly, DNA methylation profiles from CT and CB were distinct, reflecting their mesenchymal and hematopoietic stem cell origins. Variable CpGs from both unfractionated CT and its isolated cell types were more likely to be located in open seas and intronic regions than those in CB. Cell type specific CpGs in CT were enriched in intercellular matrix pathways, while those from CB were enriched in immune-related pathways. This study provides an open source reference panel for estimation and adjustment of cellular heterogeneity in CT and CB, and broadens the scope of tissue utilization assessed in future neonatal EWAS studies.

Abstract Background Genomic selection (GS) uses genome-wide markers as an attempt to accelerate genetic gain in breeding programs of both animals and plants. This approach is particularly useful for perennial crops such as oil palm, which have long breeding cycles, and for which the optimal method for GS is still under debate. In this study, we evaluated the effect of different marker systems and modeling methods for implementing GS in an introgressed dura family derived from a Deli dura x Nigerian dura (Deli x Nigerian) with 112 individuals. This family is an important breeding source for developing new mother palms for superior oil yield and bunch characters. The traits of interest selected for this study were fruit-to-bunch (F/B), shell-to-fruit (S/F), kernel-to-fruit (K/F), mesocarp-to-fruit (M/F), oil per palm (O/P) and oil-to-dry mesocarp (O/DM). The marker systems evaluated were simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs). RR-BLUP, Bayesian A, B, Cπ, LASSO, Ridge Regression and two machine learning methods (SVM and Random Forest) were used to evaluate GS accuracy of the traits. Results The kinship coefficient between individuals in this family ranged from 0.35 to 0.62. S/F and O/DM had the highest genomic heritability, whereas F/B and O/P had the lowest. The accuracies using 135 SSRs were low, with accuracies of the traits around 0.20. The average accuracy of machine learning methods was 0.24, as compared to 0.20 achieved by other methods. The trait with the highest mean accuracy was F/B (0.28), while the lowest were both M/F and O/P (0.18). By using whole genomic SNPs, the accuracies for all traits, especially for O/DM (0.43), S/F (0.39) and M/F (0.30) were improved. The average accuracy of machine learning methods was 0.32, compared to 0.31 achieved by other methods. Conclusion Due to high genomic resolution, the use of whole-genome SNPs improved the efficiency of GS dramatically for oil palm and is recommended for dura breeding programs. Machine learning slightly outperformed other methods, but required parameters optimization for GS implementation.

Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

Abstract Background Up to now, numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), however, without a consistent result. Hence we performed current systematic review and meta-analysis to clarify the controversial results. Methods Case-control studies reporting the relationship of rs9939609 A/T polymorphism and PCOS published before April 2015 were searched in Pubmed database without language restriction. Data was analyzed by Review Manager 5.2. Results A total of five studies involving 5010 PCOS patients and 5300 controls were included for further meta-analysis. The results of meta-analysis showed that the FTO gene rs9939609 A/T polymorphism was significantly different between PCOS group and control group in different gene models (For AA + AT vs. TT: OR = 1.41, 95% CI = 1.28–1.55, P

Abstract Genomic selection (GS) uses genome-wide markers to select individuals with the desired overall combination of breeding traits. A total of 1,218 individuals from a commercial population of Ulu Remis x AVROS (UR x AVROS) were genotyped using the OP200K array. The traits of interest included: shell-to-fruit ratio (S/F, %), mesocarp-to-fruit ratio (M/F, %), kernel-to-fruit ratio (K/F, %), fruit per bunch (F/B, %), oil per bunch (O/B, %) and oil per palm (O/P, kg/palm/year). Genomic heritabilities of these traits were estimated to be in the range of 0.40 to 0.80. GS methods assessed were RR-BLUP, Bayes A (BA), Cπ (BC), Lasso (BL) and Ridge Regression (BRR). All methods resulted in almost equal prediction accuracy. The accuracy achieved ranged from 0.40 to 0.70, correlating with the heritability of traits. By selecting the most important markers, RR-BLUP B has the potential to outperform other methods. The marker density for certain traits can be further reduced based on the linkage disequilibrium (LD). Together with in silico breeding, GS is now being used in oil palm breeding programs to hasten parental palm selection.

Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health.

Traditional polyamide elastomer synthesis via polycondensation of diamines and dicarboxylic acids involves high energy use and by-product mass loss. Here, we present a novel method using thiol-Michael addition click chemistry to produce these elastomers under mild conditions, marking the first use of this strategy. The polymerization involves coupling bis-acrylamide (BAA) with 3,6-dioxa-l,8-octanedithiol (DODT), catalyzed by l,5-diazabicyclo[4.3.0] non-5-ene (DBN). BAA is synthesized from polyetheramine and acrvloyl chloride, creating a compound with amide groups and carbon double bonds at chain ends. These double bonds' electron-withdrawing effect facilitates the click reaction efficiently, avoiding high energy and mass loss. The resulting polymers have a molecular weight of approximately 10,000 g/mol, verified by [sup.1]H NMR and FTIR spectroscopy, which show amide group presence. SAXS and AFM confirm nanophase separation of these groups. Tensile strength ranges from 0.235 to 0.542 MPa, decreasing with lower polyetheramine content but still showing notable elasticity. This method's low energy use, no mass loss, and good mechanical properties make it promising for developing high-performance polyamide plastics and elastomers, appealing to researchers in both academia and industry. Highlights * High elasticity, softness, and high tensile polyamide elastomer. * Thiol-Michael addition click reaction conforms to atomic economy. * Long molecular chain contains extraordinary evolution of hydrogen bonding. KEYWORDS click reaction, high elasticity, polyamide elastomer, thiol-Michael addition, 1 | INTRODUCTION Elastomers with superior elastic recovery are capable of reverting to their original form post-stretching without necessitating external assistance, a capability attributed to their distinctive structural features, such [...]