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The associations between circulating PUFA and cardiovascular risk factors and events in healthy Asian populations have been less examined robustly compared with Western populations. This systematic review aimed to summarise current evidence on the associations between n -3 and n -6 PUFA biomarkers and cardiovascular risk factors and events in healthy Asian populations. Four databases were searched for observational studies from 2010 until 2024. Twenty-three studies were eligible, which covered six Asian countries and included events ( n 7), traditional risk factors such as blood pressure and lipids ( n 4), physical signs such as arterial stiffness ( n 4), non-traditional lipid markers ( n 1), markers of inflammation ( n 4), markers of thrombosis ( n 2) and non-invasive imaging-based markers ( n 5). Biological sample types included plasma ( n 6), serum ( n 14) and erythrocyte ( n 3). Higher circulating total n -3 PUFA appeared to be associated with lower hypertension risk and specifically EPA and DHA to be associated with lower myocardial infarction risk, reduction in TAG and inflammation. Higher circulating linoleic acid was associated with improved lipid profiles and lower inflammation. Limited evidence led to inconclusive associations between circulating n -6 PUFA biomarkers and CVD events and blood pressure. No consistent associations with arterial stiffness, obesity, thrombosis and imaging-based biomarkers were observed for circulating PUFA biomarkers in Asian populations. Limited studies exist for each outcome; hence, results should be interpreted with caution. More high-quality and prospective studies in Asian populations are warranted. Several recommendations such as sample size justification and reporting of non-respondents rate are proposed for future studies.

Rare and typically severe motor speech disorders such as childhood apraxia of speech (CAS) and dysarthria affect about 1 in 1000 children. The genetic basis of these speech disorders is well-documented, with approximately 30% of children who undergo genomic testing receiving an explanatory genetic diagnosis. As more children with speech disorders are offered genetic testing, understanding parental views and experiences around genetic testing for their child is critical in providing effective pre- and post-test genetic counselling. This research explored parental attitudes, experiences, and perceived implications of pursuing genetic testing for their child with motor speech disorder. Semi-structured interviews were conducted with 20 parents of children with CAS or dysarthria who had undergone exome sequencing. Eight parents had received a genetic diagnosis for their child and 12 received uninformative genetic test results. Interviews were transcribed verbatim, co-coded, and analysed using reflexive thematic analysis. Parents were highly motivated to pursue genetic testing for their child's speech disorder due to the perceived personal, clinical, social, and financial utility in obtaining a genetic diagnosis. Regardless of testing outcome, parents experienced complex emotional responses in receiving their child's genetic test results. Parents whose child received a genetic diagnosis reported improved access to funding and clinical care; however, they also hoped for ongoing informational, clinical, and peer support in navigating the uncertainty surrounding their child's rare diagnosis. Conversely, parents who received uninformative genetic test results reported finding meaning in this test outcome, and used emotional-focused and problem-focused strategies to cope with their child's continued diagnostic odyssey., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Human Research Ethics Committee of the Royal Children’s Hospital, Melbourne, Australia (reference number: 37353)., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Background/Objectives : The emergence and dissemination of carbapenem-resistant organisms, particularly Acinetobacter baumannii and Klebsiella pneumoniae , pose a significant threat to healthcare systems worldwide. This retrospective study aims to characterise carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains in a teaching hospital and to determine the risk factors associated with patients' in-hospital mortality. Methods : A total of 90 CRAB and 63 CRKP were included in this study. Carbapenemase genes and MLST types of CRAB and CRKP were determined using specific primers. Risk factors associated with in-hospital mortality were analysed with collected data. Results: All the CRAB strains consisted of OXA carbapenemase genes, with 98% of the strains co-harbouring bla OXA-23-like and bla OXA-51-like carbapenemase genes. Conversely, bla NDM is the predominant carbapenemase gene in CRKP, followed by bla OXA-48-like carbapenemase genes. ST2 and ST20 are the dominant MLST types in CRAB and CRKP, respectively. In CRAB, multivariate analysis identified age, ethnicity, the presence of a mechanical ventilator, and patients who experienced previous exposure to clindamycin in the last 90 days as associated with an increased risk of in-hospital mortality. In contrast, older age, male, ICU admission, and the presence of an indwelling urinary catheter were significantly associated with an increased risk of mortality for patients with CRKP. Conclusions : Both CRAB and CRKP lead to high rates of mortality. The MLST profile showed that the genomic patterns of CRKP were highly diverse, whereas CRAB strains had low genetic diversity. To tackle these challenging pathogens, robust surveillance and an in-depth understanding of molecular epidemiology and genomics studies are needed to tailor infection control strategies and individualise treatment approaches.

Chronic kidney disease is a significant cause of morbidity and mortality worldwide. In recent years, Galectin-3 has been put forward as a potential biomarker of chronic kidney disease progression. This review aims to assess the clinical utility of Galectin-3 in various pathological processes leading up to chronic kidney disease such as diabetes and lupus nephritis. We conducted a systematic search on PubMed from inception to September 2023, using the search term ("Galectin-3" OR "gal-3") AND ("renal" OR "kidney"). Galectin-3 has been shown to be both pro-fibrotic and protective against renal fibrosis through various mechanisms such as apoptotic body clearance and modulation of the Wnt pathway. Studies have found associations between raised Galectin-3, incidence and progression of chronic kidney disease. In lupus nephritis, Galectin-3 may serve as a biomarker for lupus nephritis activity. Although Galectin-3 inhibits cystogenesis, there is no correlation between total kidney volume and Galectin-3 in polycystic kidney disease. The role of Galectin-3 in staging and prognostication of renal cell carcinoma is yet to be determined. Galectin-3 has potential in predicting chronic kidney disease progression, in combination with other biomarkers. However, more trials are required given that present studies demonstrate conflicting results on the relationship between Galectin-3 and clinical outcomes in chronic kidney disease patients of varying aetiologies., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

As methanol can be derived from either CO 2 or methane, methanol economy can play an important role in combating climate change. In this scenario, rapid utilization of methanol by an industrial microorganism is the first and crucial step for efficient utilization of the C1 feedstock chemical. Here, we report the development of a methylotrophic E. coli strain with a doubling time of 3.5 hours under optimal conditions, comparable or faster than native model methylotrophs Methylorubrum extorquens AM1 (T d ~4hr) and Bacillus methanolicus at 37°C (T d ~5hr). To accomplish this, we develop a bacterial artificial chromosome (BAC) with dynamic copy number variation (CNV) to facilitate overcoming the formaldehyde-induced DNA-protein cross-linking (DPC) problem in the evolution process. We track the genome variations of 75 cultures along the evolution process by next-generation sequencing, and identified the features of the fast-growing strain. After stabilization, the final strain (SM8) grows to 20 g/L of cell mass within 77 hrs in a bioreactor. This study illustrates the potential of dynamic CNV as an evolution tool and synthetic methylotrophs as a platform for sustainable biotechnological applications., (© 2024. The Author(s).)

Background: In Malaysia, an increase in non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) has been observed over the years. Previously, four NC-CRKP with increased susceptibility to ciprofloxacin in the presence of phenylalanine-arginine β-naphthylamide (PAβN) were identified. However, no contribution of the PAβN-inhibited efflux pump to carbapenem resistance was observed. All four NC-CRKP harboured non-carbapenemase β-lactamase, with two also exhibiting porin loss. In this study, we further investigated the genomic features and resistance mechanisms of these four isolates., Methods: All four NC-CRKP were subjected to whole-genome sequencing, followed by comparative genomic and phylogenetic analyses., Results: Multi-locus sequence typing (MLST) analysis divided the four NC-CRKP into different sequence types: ST392, ST45, ST14, and ST5947. Neither major nor rare carbapenemase genes were detected. Given the presence of non-carbapenemase β-lactamase in all isolates, we further investigated the potential mechanisms of resistance by identifying related chromosomal mutations. Deletion mutation was detected in the cation efflux system protein CusF. Insertion mutation was identified in the nickel/cobalt efflux protein RcnA. Missense mutation of ompK36 porin was detected in two isolates, while the loss of ompK36 porin was observed in another two isolates., Conclusions: This study revealed that NC-CRKP may confer carbapenem resistance through a combination of non-carbapenemase β-lactamase and potential chromosomal mutations including missense mutation or loss of ompK36 porin and/or a frameshift missense mutation in efflux pump systems, such as cation efflux system protein CusF and nickel/cobalt efflux protein RcnA. Our findings highlighted the significance of implementing whole-genome sequencing into clinical practice to promote the surveillance of carbapenem resistance mechanisms among NC-CRKP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Sri La Sri Ponnampalavanar, Wong, Kong, Ngoi, Karunakaran, Lau, Abdul Jabar and Teh.)

With emerging Asian-derived diet quality indices and data-driven dietary patterns available, we aimed to synthesize the various dietary patterns and quantify its association with cardiovascular diseases (CVDs) among Asian populations. We systematically searched PubMed, Embase, Scopus, and Web of Science for observational studies in South, Southeast, and East Asia. Dietary patterns were grouped "high-quality," which included high intakes of three or more of the following food groups: 1) fruits and vegetables, 2) whole grains, 3) healthy protein sources (legumes and nuts, fish and seafood, low-fat dairy, and lean meat and poultry), and 4) liquid plant oils. High-quality patterns were further subcategorized based on their derivation methods: non-Asian indices, Asian indices, data-driven patterns, and plant-based indices. Dietary patterns were grouped "low-quality," which included high intakes of two or more of the following: 5) ultraprocessed food, 6) beverages and foods with added sugars, 7) foods high in salt, and 8) alcoholic beverages. Data-driven dietary patterns characterized by animal food sources were labeled "animal-based," and studies using dietary diversity scores were labeled "diet diversity indices." Dietary patterns that could not be meaningfully categorized were summarized narratively. Study-specific effect estimates were pooled using a random-effects model. Forty-one studies were included in this review. Higher adherence to high-quality dietary patterns in the top compared with bottom tertile defined by non-Asian indices (RR: 0.78; 95% CI: 0.69, 0.88; GRADE: moderate), Asian indices (RR: 0.84; 95% CI: 0.79, 0.90; GRADE: low), and data-driven patterns (RR: 0.81; 95% CI: 0.74, 0.89; GRADE: moderate) were associated with lower CVD risk. Plant-based, low-quality, animal-based, and diet diversity indices dietary patterns were not associated with CVD. Associations of Asian diet quality indices and CVD risk were weaker than those with non-Asian indices, highlighting the need for current Asian diet quality criteria to be updated to better capture the impact of diet on CVD. The systematic review and meta-analysis was registered at PROSPERO as CRD42021244318., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Blood typing is essential for safe transfusions and is performed serologically or genetically. Genotyping predominantly focuses on coding regions, but non-coding variants may affect gene regulation, as demonstrated in the ABO, FY and XG systems. To uncover regulatory loci, we expanded a recently developed bioinformatics pipeline for discovery of non-coding variants by including additional epigenetic datasets., Methods: Multiple datasets including ChIP-seq with erythroid transcription factors (TFs), histone modifications (H3K27ac, H3K4me1), and chromatin accessibility (ATAC-seq) were analyzed. Candidate regulatory regions were investigated for activity (luciferase assays) and TF binding (electrophoretic mobility shift assay, EMSA, and mass spectrometry, MS)., Results: In total, 814 potential regulatory sites in 47 blood-group-related genes were identified where one or more erythroid TFs bound. Enhancer candidates in CR1, EMP3, ABCB6, and ABCC4 indicated by ATAC-seq, histone markers, and co-occupancy of 4 TFs (GATA1/KLF1/RUNX1/NFE2) were investigated but only CR1 and ABCC4 showed increased transcription. Co-occupancy of GATA1 and KLF1 was observed in the KEL promoter, previously reported to contain GATA1 and Sp1 sites. TF binding energy scores decreased when three naturally occurring variants were introduced into GATA1 and KLF1 motifs. Two of three GATA1 sites and the KLF1 site were confirmed functionally. EMSA and MS demonstrated increased GATA1 and KLF1 binding to the wild-type compared to variant motifs., Discussion: This combined bioinformatics and experimental approach revealed multiple candidate regulatory regions and predicted TF co-occupancy sites. The KEL promoter was characterized in detail, indicating that two adjacent GATA1 and KLF1 motifs are most crucial for transcription., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Yeasts exhibit promising potential for the microbial conversion of crude glycerol, owing to their versatility in delivering a wide range of value-added products, particularly lipids. Sweetwater, a methanol-free by-product of the fat splitting process, has emerged as a promising alternative feedstock for the microbial utilization of crude glycerol. To further optimize sweetwater utilization, we compared the growth and lipid production capabilities of 21 oleaginous yeast strains under different conditions with various glycerol concentrations, sweetwater types and pH., Results: We found that nutrient limitation and the unique carbon composition of sweetwater boosted significant lipid accumulation in several strains, in particular Rhodosporidium toruloides NRRL Y-6987. Subsequently, to decipher the underlying mechanism, the transcriptomic changes of R. toruloides NRRL Y-6987 were further analyzed, indicating potential sugars and oligopeptides in sweetwater supporting growth and lipid accumulation as well as exogenous fatty acid uptake leading to the enhanced lipid accumulation., Conclusion: Our comparative study successfully demonstrated sweetwater as a cost-effective feedstock while identifying R. toluroides NRRL Y-6987 as a highly promising microbial oil producer. Furthermore, we also suggested potential sweetwater type and strain engineering targets that could potentially enhance microbial lipid production., (© 2024. The Author(s).)

Background: The widespread use of electronic health records in the clinical and biomedical fields makes the removal of protected health information (PHI) essential to maintain privacy. However, a significant portion of information is recorded in unstructured textual forms, posing a challenge for deidentification. In multilingual countries, medical records could be written in a mixture of more than one language, referred to as code mixing. Most current clinical natural language processing techniques are designed for monolingual text, and there is a need to address the deidentification of code-mixed text., Objective: The aim of this study was to investigate the effectiveness and underlying mechanism of fine-tuned pretrained language models (PLMs) in identifying PHI in the code-mixed context. Additionally, we aimed to evaluate the potential of prompting large language models (LLMs) for recognizing PHI in a zero-shot manner., Methods: We compiled the first clinical code-mixed deidentification data set consisting of text written in Chinese and English. We explored the effectiveness of fine-tuned PLMs for recognizing PHI in code-mixed content, with a focus on whether PLMs exploit naming regularity and mention coverage to achieve superior performance, by probing the developed models' outputs to examine their decision-making process. Furthermore, we investigated the potential of prompt-based in-context learning of LLMs for recognizing PHI in code-mixed text., Results: The developed methods were evaluated on a code-mixed deidentification corpus of 1700 discharge summaries. We observed that different PHI types had preferences in their occurrences within the different types of language-mixed sentences, and PLMs could effectively recognize PHI by exploiting the learned name regularity. However, the models may exhibit suboptimal results when regularity is weak or mentions contain unknown words that the representations cannot generate well. We also found that the availability of code-mixed training instances is essential for the model's performance. Furthermore, the LLM-based deidentification method was a feasible and appealing approach that can be controlled and enhanced through natural language prompts., Conclusions: The study contributes to understanding the underlying mechanism of PLMs in addressing the deidentification process in the code-mixed context and highlights the significance of incorporating code-mixed training instances into the model training phase. To support the advancement of research, we created a manipulated subset of the resynthesized data set available for research purposes. Based on the compiled data set, we found that the LLM-based deidentification method is a feasible approach, but carefully crafted prompts are essential to avoid unwanted output. However, the use of such methods in the hospital setting requires careful consideration of data security and privacy concerns. Further research could explore the augmentation of PLMs and LLMs with external knowledge to improve their strength in recognizing rare PHI., (©You-Qian Lee, Ching-Tai Chen, Chien-Chang Chen, Chung-Hong Lee, Peitsz Chen, Chi-Shin Wu, Hong-Jie Dai. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.01.2024.)

Introduction: Patent foramen ovale (PFO) occurs in 25% of the general population and in 40% of cryptogenic ischemic stroke patients. Recent trials support PFO closure in selected patients with cryptogenic stroke. We examined the outcomes of transcatheter PFO closure in a real-world study cohort with cryptogenic stroke., Methods: Consecutive ischemic stroke patients who were classified as cryptogenic on the TOAST aetiology and diagnosed with a PFO were included. All patients underwent either transcatheter PFO closure or medical therapy. A 2:1 propensity score matching by sex and Risk-of-Paradoxical-Embolism (RoPE) score was performed. Multivariable regression models adjusted for sex and RoPE score., Results: Our cohort comprised 232 patients with mean age 44.3 years (SD 10.8) and median follow-up 1486.5 days. 33.2% were female. PFO closure (n=84) and medical therapy (n=148) groups were well-matched with <10% mean-difference in sex and RoPE score. Two patients in the treated group (2.4%) and seven in the control group (4.7%) had a recurrent ischemic stroke event. Multivariable Cox regression demonstrated a hazard-ratio of 0.26 (95%CI 0.03-2.13, P=0.21) for PFO closure compared to control. The incidence of atrial fibrillation (AF) detected post-PFO closure was similar between the treated and control (1.19% vs 1.35%, multivariable logistic regression odds-ratio 0.90, 95%CI 0.04-9.81, P=0.94). There were no major periprocedural complications documented. The difference in restricted mean survival-time free from stroke at two years between treated and control was 26.2 days (95%CI 5.52-46.85, P=0.013)., Conclusions: In this Asian cohort, we report a low incidence of ischemic stroke recurrence and new-onset AF in patients who underwent PFO closure. When compared to the medical therapy group, there was no significant difference in the incidence of stroke recurrence and new-onset AF. Further studies involving larger real-world cohorts are warranted to identify patients who are more likely to benefit from PFO closure., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance., Methods: Therefore, an inventory surveillance of the ESBL- Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated., Results: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The bla CTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring bla CTX-M-1 only, 27 isolates (21.3%) co-harbouring bla CTX-M-1 and bla TEM , and ten isolates (7.9%) co-harbouring bla CTX-M-1, bla TEM and bla SHV . A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes., Competing Interests: Cindy Shuan Ju Teh is an Academic Editor for PeerJ. Loong Hua Tee and Kin Chong Leong were employed by Shionogi Singapore Pte Ltd at the time of the study., (© 2023 Yap et al.)

Limited attention has been given to the role of cultural orientation towards different ethnic groups in multi-ethnic settings without a dominant host culture. We evaluated whether acculturation levels, reflecting cultural orientation towards other ethnic groups, were associated with obesity and related lifestyle behaviors in a cosmopolitan Asian population. We conducted the current study based on data from the Singapore Multi-Ethnic Cohort ( N = 10,622) consisting of ethnic Chinese, Malays, and Indians aged 21 to 75 years. Multivariable linear and logistic regression analyses were used to examine associations between the acculturation level (z-score), obesity, and related lifestyle behaviors, including dietary habits and physical activity. A higher acculturation level was directly associated with a higher prevalence of obesity among Chinese, whereas an inverse association was found for ethnic Indians, and no significant association in Malays. In ethnic Malays, greater acculturation was significantly associated with higher dietary quality and less sedentary time. Furthermore, a high acculturation level was significantly associated with higher sugar-sweetened beverage consumption and more leisure-time PA in all ethnic groups. Our findings suggest that greater cultural orientation towards other ethnic groups was associated with convergence in obesity levels. More research is required to understand how acculturation affects obesity-related lifestyle factors in multi-ethnic settings., Competing Interests: The authors declare no conflict of interest.

Genetic determinants underlying most human blood groups are now clarified but variation in expression levels remains largely unexplored. By developing a bioinformatics pipeline analyzing GATA1/Chromatin immunoprecipitation followed by sequencing (ChIP-seq) datasets, we identify 193 potential regulatory sites in 33 blood-group genes. As proof-of-concept, we aimed to delineate the low-expressing complement receptor 1 (CR1) Helgeson phenotype on erythrocytes, which is correlated with several diseases and protects against severe malaria. We demonstrate that two candidate CR1 enhancer motifs in intron 4 bind GATA1 and drive transcription. Both are functionally abolished by naturally-occurring SNVs. Erythrocyte CR1-mRNA and CR1 levels correlate dose-dependently with genotype of one SNV (rs11117991) in two healthy donor cohorts. Haplotype analysis of rs11117991 with previously proposed markers for Helgeson shows high linkage disequilibrium in Europeans but explains the poor prediction reported for Africans. These data resolve the longstanding debate on the genetic basis of inherited low CR1 and form a systematic starting point to investigate the blood group regulome., (© 2023. Springer Nature Limited.)

Introduction: A dental technologist is one of the most essential allied dental health professionals and the dental technology curriculum should be comprehensively reviewed on a regular basis. This study aims to compare the only existing Bachelor of Dental Technology (BDT) curriculum in Malaysia with BDT programmes offered by other well-established universities, and map out the similarities and differences, as well as to explore future recommendations and propose a new curriculum framework., Materials and Methods: A descriptive analysis was carried out using Laurie Brady's four-stage strategy. First, available curriculum materials were collected from four different institutions' electronic webpage: AIMST (Malaysia), GU (Australia), UO (New Zealand) and CMU (United Kingdom), and then compared based on three key domains: curriculum contents, teaching and learning strategies and assessments. Following that, the similarities and differences between various curricula were identified. Future recommendations and a curriculum framework were then proposed., Results: The core BDT curriculum content is concurred upon by all four universities, with an emphasis on basic sciences, laboratory materials, practical sessions and research projects. However, the credit weightage for each course or module varied across the four institutions, with some offering unique subjects and implementing different teaching methods and assessments. A simple BDT curriculum framework with a proposed syllabus was designed based on the three key domains and future recommendations for curriculum improvement were explored., Conclusion: The present study identified several areas for Malaysian BDT curriculum development and improvement. The proposed framework can be a guide for Malaysian dental schools in designing a comprehensive dental technology programme., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The biomass equation is a critical component in genome-scale metabolic models (GEMs): it is used as the de facto objective function in flux balance analysis (FBA). This equation accounts for the quantities of all known biomass precursors that are required for cell growth based on the macromolecular and monomer compositions measured at certain conditions. However, it is often reported that the macromolecular composition of cells could change across different environmental conditions and thus the use of the same single biomass equation in FBA, under multiple conditions, is questionable. Herein, we first investigated the qualitative and quantitative variations of macromolecular compositions of three representative host organisms, Escherichia coli , Saccharomyces cerevisiae and Cricetulus griseus , across different environmental/genetic variations. While macromolecular building blocks such as RNA, protein, and lipid composition vary notably, changes in fundamental biomass monomer units such as nucleotides and amino acids are not appreciable. We also observed that flux predictions through FBA is quite sensitive to macromolecular compositions but not the monomer compositions. Based on these observations, we propose ensemble representations of biomass equation in FBA to account for the natural variation of cellular constituents. Such ensemble representations of biomass better predicted the flux through anabolic reactions as it allows for the flexibility in the biosynthetic demands of the cells. The current study clearly highlights that certain component of the biomass equation indeed vary across different conditions, and the ensemble representation of biomass equation in FBA by accounting for such natural variations could avoid inaccuracies that may arise from in silico simulations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Cutibacterium acnes , one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The current limitations of acne treatment using antibiotics have caused an urgent need to develop a systematic strategy for selectively targeting C. acnes , which can be achieved by characterizing their cellular behaviors under various skin environments. To this end, we developed a genome-scale metabolic model (GEM) of virulent C. acnes , i CA843, based on the genome information of a relevant strain from ribotype 5 to comprehensively understand the pathogenic traits of C. acnes in the skin environment. We validated the model qualitatively by demonstrating its accuracy prediction of propionate and acetate production patterns, which were consistent with experimental observations. Additionally, we identified unique biosynthetic pathways for short-chain fatty acids in C. acnes compared to other GEMs of acne-inducing skin pathogens. By conducting constraint-based flux analysis under endogenous carbon sources in human skin, we discovered that the Wood-Werkman cycle is highly activated under acnes-associated skin condition for the regeneration of NAD, resulting in enhanced propionate production. Finally, we proposed potential anti- C. acnes targets by using the model-guided systematic framework based on gene essentiality analysis and protein sequence similarity search with abundant skin microbiome taxa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Lee, Lee, Lee, Rho, Kim, Seo, Youn, Hwang, Kang, Lee, Park and Lee.)

Background: Evidence is accumulating that intake of animal-based and plant-based proteins has different effects on cardiometabolic health, but less is known about the health effect of isocaloric substitution of animal-based and plant-based proteins. Data from Asian populations are limited., Objectives: This study aimed to evaluate the effects of isocaloric substitution of total plant-based proteins for total and various animal-based protein food groups and to evaluate the effects of substituting protein from legumes and pulses for various animal-based protein food groups on cardiovascular disease (CVD) risk factors and predicted 10-y CVD risk., Methods: We conducted a cross-sectional analysis using data collected from 9211 Singapore residents (aged 21-75 y) from the Singapore Multi-Ethnic Cohort. Data on sociodemographic and lifestyle factors were collected using questionnaires. Dietary intakes were assessed using a validated FFQ. BMI, waist circumference, and blood pressure were measured during a physical examination, and blood samples were collected to measure lipid profiles. Associations were assessed by substitution models using a multiple linear regression analysis., Results: Isocaloric substitution of total plant-based proteins for total and all specific animal-based protein food groups were associated with lower BMI (β: -0.30; 95% CI: -0.38, -0.22), waist circumference (β: -0.85; 95% CI: -1.04, -0.66), and LDL cholesterol concentrations (β: -0.06; 95% CI: -0.08, -0.05) (P < 0.0056). Replacement of processed meat and processed seafood proteins with total plant-based proteins was associated with improvement in most CVD risk factors and predicted 10-y CVD risk. Replacement of oily fish with legume proteins was associated with lower HDL cholesterol and higher TG concentrations., Conclusions: The substitution of plant-based proteins for animal-based proteins, especially from processed meat and processed seafood, was inversely associated with the established CVD risk factors such as BMI, waist circumference, and lipid concentrations and predicted 10-y CVD risk. These findings warrant further investigation in independent studies in other Asian populations., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies., (© 2022 National Society of Genetic Counselors.)

Introduction: Patent foramen ovale (PFO) is a potential source of cardiac embolism in cryptogenic ischemic stroke, but it may also be incidental. Right-to-left shunt (RLS) size may predict PFO-related stroke, but results have been controversial. In this cohort study of medically-managed PFO patients with cryptogenic stroke, we aimed to investigate the association of shunt size with recurrent stroke, mortality, newly detected atrial fibrillation (AF), and to identify predictors of recurrent stroke., Methods: Patients with cryptogenic stroke who screened positive for a RLS using a transcranial Doppler bubble study were included. Patients who underwent PFO closure were excluded. Subjects were divided into two groups: small (Spencer Grade 1, 2, or 3; n = 135) and large (Spencer Grade 4 or 5; n = 99) shunts. The primary outcome was risk of recurrent stroke, and the secondary outcomes were all-cause mortality and newly detected AF., Results: The study cohort included 234 cryptogenic stroke patients with medically-managed PFO. The mean age was 50.5 years, and 31.2% were female. The median period of follow-up was 348 (IQR 147-1096) days. The rate of recurrent ischemic stroke was higher in patients with large shunts than in those with small shunts (8.1% vs. 2.2%, p = 0.036). Multivariate analyses revealed that a large shunt was significantly associated with an increased risk of recurrent ischemic stroke [aOR 4.09 (95% CI 1.04-16.0), p = 0.043]., Conclusions: In our cohort of cryptogenic stroke patients with medically managed PFOs, those with large shunts were at a higher risk of recurrent stroke events, independently of RoPE score and left atrium diameter.

Introduction: A patent foramen ovale (PFO) may coexist with other potential embolic sources (PESs) in patients with embolic stroke of undetermined source (ESUS), leading to difficulty in attributing the stroke to either the PFO or other PESs. We aimed to investigate the prevalence and predictors of concomitant PESs in ESUS patients with PFOs., Methods: A retrospective cohort study was conducted in a tertiary stroke centre. Consecutive patients with ESUS and a concomitant PFO admitted between 2012 and 2021 were included in the study. Baseline characteristics and investigations as a part of stroke workup including echocardiographic and neuroimaging data were collected. PESs were adjudicated by 2 independent neurologists after reviewing the relevant workup., Results: Out of 1,487 ESUS patients, a total of 309 patients who had a concomitant PFO with mean age of 48.8 ± 13.2 years were identified during the study period. The median Risk of Paradoxical Embolism (RoPE) score for the study cohort was 6 (IQR 5-7.5). Of the 309 patients, 154 (49.8%) only had PFO, 105 (34.0%) patients had 1 other PES, 34 (11.0%) had 2 PES, and 16 (5.2%) had 3 or more PES. The most common PESs were atrial cardiopathy (23.9%), left ventricular dysfunction (22.0%), and cardiac valve disease (12.9%). The presence of additional PESs was associated with age ≥60 years (p < 0.001), RoPE score ≤6 (p ≤0.001), and the presence of comorbidities including diabetes mellitus (p = 0.004), hypertension (p≤ 0.001), and ischaemic heart disease (p = 0.011)., Conclusion: A large proportion of ESUS patients with PFOs had concomitant PESs. The presence of concomitant PESs was associated with older age and a lower RoPE score. Further, large cohort studies are warranted to investigate the significance of the PES and their overlap with PFOs in ESUS., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Lactic acid bacteria (LAB) are well known to elicit health benefits in humans, but their functional metabolic landscapes remain unexplored. Here, we analyze differences in growth, intestinal persistence, and postbiotic biosynthesis of six representative LAB and their interactions with 15 gut bacteria under 11 dietary regimes by combining multi-omics and in silico modeling. We confirmed predictions on short-term persistence of LAB and their interactions with commensals using cecal microbiome abundance and spent-medium experiments. Our analyses indicate that probiotic attributes are both diet and species specific and cannot be solely explained using genomics. For example, although both Lacticaseibacillus casei and Lactiplantibacillus plantarum encode similarly sized genomes with diverse capabilities, L. casei exhibits a more desirable phenotype. In addition, "high-fat/low-carb" diets more likely lead to detrimental outcomes for most LAB. Collectively, our results highlight that probiotics are not "one size fits all" health supplements and lay the foundation for personalized probiotic design., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ensuring that the elderly drink adequate fluids to meet their recommended daily allowance is often a challenge, especially among the elderly in hospitals and long-term care settings. The complex interplay of biological, medical and psychosocial factors that cause the elderly to become dehydrated is difficult to tackle especially in care settings where there is a staff shortage and heavy workload. The team realised that 90% of the elderly inpatients in the general ward of a teaching hospital in Singapore were not drinking enough to meet their needs, despite the hot and humid weather. Reasons which contributed to inadequate fluid intake included human resources, environmental, patient and system factors. Strategies were put in place to improve fluid intake but were not successful, due to staff shortage and time constraints. The team ended up innovating and producing a dysphagia cup to improve fluid intake, promote independence among patients while encouraging them to drink more, improve nursing efficiency, reduce caregiver burden and reduce aspiration risk. The cup was able to meet all the expectations with good feedback from the care team, patients and their families., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia from January 2013 to October 2019. During the study period, 54 NC-CRKP-infected/colonised patients' isolates were obtained. Clinical parameters were assessed in 52 patients. The all-cause in-hospital mortality rate among NC-CRKP patients was 46.2% (24/52). Twenty-three (44.2%) patients were infected, while others were colonised. Based on the Charlson Comorbidity Index (CCI) score, 92.3% (48/52) of the infected/colonised patients had a score of ≥ 1. Resistance genes found among the 54 NC-CRKP isolates were bla TEM , bla SHV , bla CTX-M , bla OXA , and bla DHA . Porin loss was detected in 25/54 (46.3%) strains. None of the isolated strains conferred carbapenem resistance through the efflux pumps system. In conclusion, only 25/54 (46.3%) NC-CRKP conferred carbapenem resistance through a combination of porin loss and the acquisition of non-carbapenemase resistance mechanisms. The carbapenem resistance mechanisms for the remaining strains (53.7%) should be further investigated as rapid identification and distinction of the NC-CRKP mechanisms enable optimal treatment and infection control efforts.

With the advent of poly-ADP-ribose polymerase inhibitor (PARPi) therapies, the focus of genetic testing for breast, ovarian, and other cancers has shifted from risk management to treatment decision-making in high-resource settings. Due to the shortage of genetic counselors worldwide, alternative ways of delivering genetic counseling have been explored, including training nongenetics healthcare professionals (NGHPs) to provide genetic counseling. However, little is known about the feasibility of adopting such models in healthcare settings with insufficient specialists, where population health literacy is low and where access to new therapies may be limited. In this study, we evaluated the attitudes, considerations, and self-efficacy of oncologists, breast surgeons, and general surgeons in mainstreaming breast cancer genetic counseling in Malaysia, a middle-income Asian country with a universal healthcare system. We developed a 32-item survey via a modified Delphi method, which was then distributed via a purposive and network sampling approach. While 77% of respondents expressed interest in providing breast cancer genetic counseling, 85% preferred to refer patients directly to genetic services for genetic counseling and testing. The main considerations for mainstreaming were the cost of genetic testing and PARPi therapy, as well as the availability of support from genetics professionals. Respondents reported a lack of confidence in communicating genetic risk, particularly to patients with poor health literacy, and in the clinical management of patients with variants of uncertain significance. Our results highlight the urgent need to train more NGHPs in providing genetic counseling and testing in low-to-middle income countries, and suggest that the mainstay for genetic counseling in this setting may be for risk management rather than access to PARPi therapy., (© 2022 National Society of Genetic Counselors.)

Objective: The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) Program is a diabetes prevention trial comparing the diabetes conversion rate at 3 years between the intervention group, which receives the incentivized lifestyle intervention program with stepwise addition of metformin, and the control group, which receives the standard of care. We describe the baseline characteristics and compare Pre-DICTED participants with other diabetes prevention trials cohort., Research Design and Methods: Participants were aged between 21 and 64 years, overweight (body mass index (BMI) ≥23.0 kg/m 2 ), and had pre-diabetes (impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT))., Results: A total of 751 participants (53.1% women) were randomized. At baseline, mean (SD) age was 52.5 (8.5) years and mean BMI (SD) was 29.0 (4.6) kg/m 2 . Twenty-three per cent had both IFG and IGT, 63.9% had isolated IGT, and 13.3% had isolated IFG. Ethnic Asian Indian participants were more likely to report a family history of diabetes and had a higher waist circumference, compared with Chinese and Malay participants. Women were less likely than men to meet the physical activity recommendations (≥150 min of moderate-intensity physical activity per week), and dietary intake varied with both sex and ethnicity. Compared with other Asian diabetes prevention studies, the Pre-DICTED cohort had a higher mean age and BMI., Conclusion: The Pre-DICTED cohort represents subjects at high risk of diabetes conversion. The study will evaluate the effectiveness of a community-based incentivized lifestyle intervention program in an urban Asian context., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Studies examining associations between dietary patterns and Framingham risk score (FRS) and predicted 10-year cardiovascular diseases (CVD) risk in an Asian population are lacking. This study aimed to identify a posteriori dietary patterns across three major ethnic groups in Singapore and ascertain their associations with locally modified FRS and predicted 10-year CVD risk., Methods and Results: This cross-sectional study included 8594 Singapore residents (aged 21-75 years) from the Singapore Multi-Ethnic Cohort. Data on sociodemographic and lifestyle factors were collected via questionnaires. Food consumption was assessed using a validated Food Frequency Questionnaire. Dietary patterns were identified using principal component analysis and associations with CVD risk factors, FRS and predicted CVD risk (%) were analysed using multiple linear and logistic regression. Four dietary patterns emerged that explained 25.6% of variance. The 'processed food and sugar-sweetened beverages' pattern was significantly associated with higher FRS (β: 0.13; 95% CI: 0.04, 0.23), while the 'ethnic breads, legumes and nuts' (β: 0.13; 95% CI: 0.22, -0.04) and 'whole grains, fruit and dairy' (β: 0.17; 95% CI: 0.24, -0.10) patterns were significantly associated with lower FRS. The 'meat and vegetables' pattern was not significantly associated with FRS. Increased adherence to the 'whole grains, fruit and dairy' pattern was associated with lower odds of having predicted CVD risk of ≥10% (p-trend: 0.03)., Conclusion: Adherence to the 'ethnic breads, legumes and nuts' and 'whole grains, fruit and dairy' patterns was associated with a lower predicted CVD risk, and an inverse association for the 'processed food and sugar-sweetened beverages' pattern in an Asian population. These findings can inform the development of culturally sensitive dietary interventions to prevent CVD., Competing Interests: Declaration of competing interest None of the authors has a conflict of interest to declare., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Electronic health records (EHRs) at medical institutions provide valuable sources for research in both clinical and biomedical domains. However, before such records can be used for research purposes, protected health information (PHI) mentioned in the unstructured text must be removed. In Taiwan's EHR systems the unstructured EHR texts are usually represented in the mixing of English and Chinese languages, which brings challenges for de-identification. This paper presented the first study, to the best of our knowledge, of the construction of a code-mixed EHR de-identification corpus and the evaluation of different mature entity recognition methods applied for the code-mixed PHI recognition task.

Purpose: Few studies have described adherence to dietary patterns over time in women of childbearing age. This study aims to describe, examine the stability and changes in dietary patterns between pregnancy and 6 years post-pregnancy and the sociodemographic and lifestyle factors influencing the adherence over time., Methods: During pregnancy and at 6 years post-pregnancy, 24-h recalls and food frequency questionnaires were collected, respectively, from 709 women. Data on sociodemographic and lifestyle factors were collected via questionnaires. Dietary patterns were identified using principal component analysis and stability assessed using Pearson's correlation coefficients (r) and Cohen's weighted kappa (κ). Associations with sociodemographic characteristics were assessed by multiple logistic regression., Results: The 'Fruits, Vegetables and Legumes' (FVL) and 'Seafood, Noodle, Soup' (SNS) patterns were identified at both time points, with low correlation for the dietary pattern z scores (r 0.2 and 0.3, respectively) and modest agreement in tertile assignment, suggesting poor stability. An 'unhealthy' pattern was only observed at 6 years post-pregnancy. Women who showed increased adherence to FVL pattern had higher educational attainment and exhibited healthy lifestyle behaviours. Women who had gestational diabetes during pregnancy were less likely to decrease adherence to FVL pattern over time. Women who adhered more closely to the 'unhealthy' pattern at 6 years post-pregnancy tended to be younger, of Malay ethnicity, had lower socioeconomic status, were less physically active and had additional pregnancies., Conclusions: Dietary habits of women became less healthy during the transition from pregnancy to 6 years post-pregnancy. However, results should be interpreted with caution due to the different dietary assessment tools used at the two time points., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

There is an increasing number of cancer patients undertaking treatment-focused genetic testing despite not having a strong family history or high a priori risk of being carriers because of the decreasing cost of genetic testing and development of new therapies. There are limited studies on the psychosocial outcome of a positive result among breast cancer patients who are at low a priori risk, particularly in women of Asian descent. Breast cancer patients enrolled under the Malaysian Breast Cancer Genetic Study between October 2002 and February 2018 were tested for BRCA1, BRCA2 and PALB2 genes. All 104 carriers identified were invited by a research genetic counsellor for result disclosure. Of the 104 carriers, 64% (N = 66) had low a priori risk as determined by PENN II scores. Psychosocial, risk perception and health behaviour measures survey were conducted at baseline (pre-result disclosure), and at two to six weeks after result disclosure. At baseline, younger carriers with high a priori risk had higher Cancer Worry Scale scores than those with low a priori risk but all scores were within acceptable range. Around 75% and 55% of high a priori risk carriers as well as 80% and 67% of low a priori risk carriers had problems in the "living with cancer" and "children" psychosocial domains respectively. All carriers regardless of their a priori risk demonstrated an improved risk perception that also positively influenced their intent to undergo risk management procedures. This study has shown that with sufficient counselling and support, low a priori risk carriers are able to cope psychologically, have improved perceived risk and increased intent for positive health behaviour despite having less anticipation from a family history prior to knowing their germline carrier status., Competing Interests: The authors have declared that no competing interests exist.

Chronic respiratory diseases are major contributors to the global burden of disease. While understanding of these diseases has improved, treatment guidelines have continued to rely on severity and exacerbation-based approaches. A new personalised approach, termed the "treatable traits" approach, has been suggested to address the limitations of the existing treatment strategies. We aim to systematically review the current evidence regarding treatable traits in chronic respiratory diseases and to identify gaps in the current literature. We searched the PubMed and Embase databases and included studies on treatable traits and chronic respiratory diseases. We then extracted information on prevalence, prognostic implications, treatment options and benefits from these studies. A total of 58 papers was included for review. The traits identified were grouped into five broad themes: physiological, biochemical, psychosocial, microbiological, and comorbidity traits. Studies have shown advantages of the treatable traits paradigm in the clinical setting. However, few randomised controlled trials have been conducted. Findings from our review suggest that multidisciplinary management with therapies targeted at treatable traits has the potential to be efficacious when added to the best practices currently implemented. This paradigm has the potential to improve the holistic care of chronic respiratory diseases.

Aims: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards., Methods: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year., Results: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001)., Conclusions: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections., Clinical Trial Registration: ClinicalTrial.gov, NCT04347395., (© 2021. European Geriatric Medicine Society.)

Introduction: Suicide is a pressing psychiatric concern worldwide with no established biomarker. While there is some evidence of the clinical utility of functional near-infrared spectroscopy (fNIRS) in assessing and predicting suicidality, no systematic review of such evidence has been conducted to date. Therefore, this review aimed to systematically review and gather evidence from existing studies that used fNIRS signals to assess suicidality and its associated changes in the brain, and those that examined how such signals correlated with suicide symptomatology. Methods: PubMed, EMBASE, and Cochrane Library databases were used in a systematic literature search for English-language articles published between 2000 and December 19, 2020 that focused on the utility of fNIRS for (i) assessing suicidality and its associated changes in the brain, and (ii) correlating with suicide symptomatology. Studies were included if they utilised fNIRS to evaluate variations in fNIRS-measured cerebral hemodynamic responses in patients with different mental disorders (e.g., major depressive disorder, schizophrenia), as well as in healthy controls, of any age group. Quality of evidence was assessed using the Newcastle-Ottawa quality assessment scale. Results: A total of 7 cross-sectional studies were included in this review, all of which had acceptable quality. Across all studies, fNIRS demonstrated reduced cerebral hemodynamic changes in suicidal individuals when compared to non-suicidal individuals. One study also demonstrated the potential of fNIRS signals in correlating with the severity of suicidality. Conclusions: This review provides a comprehensive, updated review of evidence supporting the clinical utility of fNIRS in the assessment and prediction of suicidality. Further studies involving larger sample sizes, standardised methodology, and longitudinal follow-ups are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Tay and Ho.)

Curcumin analogs with excellent biological properties have been synthesized to address and overcome the poor pharmacokinetic profiles of curcumin. This study aims to investigate the cytotoxicity, anti-proliferative, and apoptosis-inducing ability of curcumin analog, MS13 on human glioblastoma U-87 MG, and neuroblastoma SH-SY5Y cells, and to examine the global proteome changes in these cells following treatment. Our current findings showed that MS13 induced potent cytotoxicity and anti-proliferative effects on both cells. Increased caspase-3 activity and decreased bcl-2 concentration upon treatment indicate that MS13 induces apoptosis in these cells in a dose- and time-dependent manner. The label-free shotgun proteomic analysis has defined the protein profiles in both glioblastoma and neuroblastoma cells, whereby a total of nine common DEPs, inclusive of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), alpha-enolase (ENO1), heat shock protein HSP 90-alpha (HSP90AA1), Heat shock protein HSP 90-beta (HSP90AB1), Eukaryotic translation initiation factor 5A-1 (EFI5A), heterogenous nuclear ribonucleoprotein K (HNRNPK), tubulin beta chain (TUBB), histone H2AX (H2AFX), and Protein SET were identified. Pathway analysis further elucidated that MS13 may induce its anti-tumor effects in both cells via the common enriched pathways, "Glycolysis" and "Post-translational protein modification." Conclusively, MS13 demonstrates an anti-cancer effect that may indicate its potential use in the management of brain malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Rajadurai, Abas, Othman and Naidu.)

Background: Gastrointestinal carriage of multidrug resistant (MDR) Gram-negative bacilli, especially Klebsiella pneumoniae and Escherichia coli, was highly associated with severe nosocomial infections. The main objectives of this study were to determine the clonal relatedness of intestinal carriage and transmission risk factors of MDR E. coli and K. pneumoniae amongst preterm infants admitted to the neonatal intensive care unit (NICU)., Methods: A prospective cohort study of preterm infants with gestational age < 37 weeks was conducted in the NICU of the University of Malaya Medical Centre (UMMC). Infants' stool specimens were collected on day 1 (meconium), week 1, week 2, week 8 and week 10 during their admission (from 1st June to 31st August 2017) until discharge. The presence and antibiotic resistance pattern of MDR E. coli and K. pneumoniae were determined. Strain clonality and relatedness were explored via pulsed-field gel electrophoresis (PFGE) fingerprints. The risk factors for MDR strains acquisition were evaluated using the Cox proportional-hazards model and Firth logistic regression., Results: A total of 139 stool specimens were obtained from 50 subjects. Twenty-six (52%) infants were colonized with MDR K. pneumoniae and/or E. coli. High clonal dissemination between two clusters of ESBL-producing K. pneumoniae strains was seen from PFGE profile. We detected a persistent, dominant, aminoglycosides-resistant strains cluster (cluster B), which harbored bla TEM , bla SHV , bla OXA-1 , bla CTX-M-1 , ompK35 and ompK36 genes. Infants born to women who were anemic in pregnancy [OR = 0.01 (CI = 0.00-0.39), P-value = 0.042] and infants exposed to penicillin/β-lactams group antibiotics during the first week of life [OR = 0.02 (CI = 0.02-0.32), P-value = 0.013] were found to have a lower risk of MDR K. pneumoniae and E. coli colonization., Conclusions: The prevalence of dominant aminoglycosides-resistant strains cluster in the NICU is alarming. Awareness of and vigilance for the dominant cluster found will enable the reduction of cross-transmission amongst high-risk infants., Competing Interests: Declaration of competing interest All authors declared no competing of interest in this study., (Copyright © 2020. Published by Elsevier B.V.)

Suboptimal nutrition during pregnancy is recognised as a significant modifiable determinant in the development of chronic disease in offspring in later life. The current study aimed: (i) to assess the dietary intakes of pregnant Indigenous Australian women against national recommendations and (ii) to investigate the associations between maternal nutrition during pregnancy and the growth of the offspring, including kidney development in late gestation in the Gomeroi gaaynggal cohort ( n = 103). Maternal dietary intake in the third trimester was assessed using the Australian Eating Survey Food Frequency Questionnaire. Estimated fetal weight (EFW) and kidney size were obtained by ultrasound. Birth weight was retrieved from hospital birth records. Of the five key nutrients for optimal reproductive health (folate, iron, calcium, zinc and fibre), the nutrients with the highest percentage of pregnant women achieving the nutrient reference values (NRVs) were zinc (75.7%) and folate (57.3%), whereas iron was the lowest. Only four people achieved all NRVs (folate, iron, calcium, zinc and fibre) important in pregnancy. Sodium and saturated fat intake exceeded recommended levels and diet quality was low, with a median score of 28 out of 73 points. After adjusting for smoking and pre-pregnancy body mass index, only maternal intake of retinol equivalents and the proportion of energy from nutrient-dense or energy-dense, nutrient-poor (EDNP) foods were associated with fetal growth. EFW decreased by 0.13 g and birth weight decreased by 0.24 g for every µg increase in maternal dietary retinol intake. Interestingly, EFW, but not actual birth weight, was positively associated with percentage energy from nutrient dense foods and negatively associated with percentage energy from EDNP foods. Dietary supplement usage was associated with increased birthweight, most significantly iron and folate supplementation. Current dietary intakes of pregnant Australian women from this cohort do not align with national guidelines. Furthermore, current findings show that maternal retinol intake and diet composition during pregnancy can influence fetal growth, but not fetal kidney growth in late gestation. Strategies that aim to support and optimise nutrient intakes of Indigenous pregnant women are urgently needed. Future studies with long-term follow-up of the children in the current cohort to assess renal damage and blood pressure are imperative.

The design principle of establishing an intracellular protein gradient for asymmetric cell division is a long-standing fundamental question. While the major molecular players and their interactions have been elucidated via genetic approaches, the diversity and redundancy of natural systems complicate the extraction of critical underlying features. Here, we take a synthetic cell biology approach to construct intracellular asymmetry and asymmetric division in Escherichia coli, in which division is normally symmetric. We demonstrate that the oligomeric PopZ from Caulobacter crescentus can serve as a robust polarized scaffold to functionalize RNA polymerase. Furthermore, by using another oligomeric pole-targeting DivIVA from Bacillus subtilis, the newly synthesized protein can be constrained to further establish intracellular asymmetry, leading to asymmetric division and differentiation. Our findings suggest that the coupled oligomerization and restriction in diffusion may be a strategy for generating a spatial gradient for asymmetric cell division.

The introduction of pre-trained language models in natural language processing (NLP) based on deep learning and the availability of electronic health records (EHRs) presents a great opportunity to transfer the "knowledge" learned from data in the general domain to enable the analysis of unstructured textual data in clinical domains. This study explored the feasibility of applying NLP to a small EHR dataset to investigate the power of transfer learning to facilitate the process of patient screening in psychiatry. A total of 500 patients were randomly selected from a medical center database. Three annotators with clinical experience reviewed the notes to make diagnoses for major/minor depression, bipolar disorder, schizophrenia, and dementia to form a small and highly imbalanced corpus. Several state-of-the-art NLP methods based on deep learning along with pre-trained models based on shallow or deep transfer learning were adapted to develop models to classify the aforementioned diseases. We hypothesized that the models that rely on transferred knowledge would be expected to outperform the models learned from scratch. The experimental results demonstrated that the models with the pre-trained techniques outperformed the models without transferred knowledge by micro-avg. and macro-avg. F-scores of 0.11 and 0.28, respectively. Our results also suggested that the use of the feature dependency strategy to build multi-labeling models instead of problem transformation is superior considering its higher performance and simplicity in the training process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dai, Su, Lee, Zhang, Wang, Kuo and Wu.)

Background: Identifying and extracting family history information (FHI) from clinical reports are significant for recognizing disease susceptibility. However, FHI is usually described in a narrative manner within patients' electronic health records, which requires the application of natural language processing technologies to automatically extract such information to provide more comprehensive patient-centered information to physicians., Objective: This study aimed to overcome the 2 main challenges observed in previous research focusing on FHI extraction. One is the requirement to develop postprocessing rules to infer the member and side information of family mentions. The other is to efficiently utilize intrasentence and intersentence information to assist FHI extraction., Methods: We formulated the task as a sequential labeling problem and propose an enhanced relation-side scheme that encodes the required family member properties to not only eliminate the need for postprocessing rules but also relieve the insufficient training instance issues. Moreover, an attention-based neural network structure was proposed to exploit cross-sentence information to identify FHI and its attributes requiring cross-sentence inference., Results: The dataset released by the 2019 n2c2/OHNLP family history extraction task was used to evaluate the performance of the proposed methods. We started by comparing the performance of the traditional neural sequence models with the ordinary scheme and enhanced scheme. Next, we studied the effectiveness of the proposed attention-enhanced neural networks by comparing their performance with that of the traditional networks. It was observed that, with the enhanced scheme, the recall of the neural network can be improved, leading to an increase in the F score of 0.024. The proposed neural attention mechanism enhanced both the recall and precision and resulted in an improved F score of 0.807, which was ranked fourth in the shared task., Conclusions: We presented an attention-based neural network along with an enhanced tag scheme that enables the neural network model to learn and interpret the implicit relationship and side information of the recognized family members across sentences without relying on heuristic rules., (©Hong-Jie Dai, You-Qian Lee, Chandini Nekkantti, Jitendra Jonnagaddala. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 01.12.2020.)

Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent pathogen causing invasive infections such as bacteraemia. The continued excessive use of antibiotics to treat MRSA infections has resulted in the evolution of antimicrobial resistant of S. aureus. This study aims to perform a comparative evaluation of changing trends in molecular epidemiology of MRSA and clinical characteristics of patients. This study shows that ST22-MRSA-IV has gradually replaced ST239-MRSA-III as the predominant MRSA clone in the tertiary teaching hospital studied. Independent predictors of mortality among patients included devices in situ at the time of infection, pre-exposure to macrolides, catheter-related bloodstream infection and mono-microbial infection. Hence, our study affirmed community-associated MRSA, which was previously identified from individuals without any exposure to healthcare settings, has now emerged in healthcare settings, causing healthcare-associated MRSA infections., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Probiotics are live beneficial microorganisms that can be consumed in the form of dairy and food products as well as dietary supplements to promote a healthy balance of gut bacteria in humans. Practically, the main challenge is to identify and select promising strains and formulate multi-strain probiotic blends with consistent efficacy which is highly dependent on individual dietary regimes, gut environments, and health conditions. Limitations of current in vivo and in vitro methods for testing probiotic strains can be overcome by in silico model guided systems biology approaches where genome scale metabolic models (GEMs) can be used to describe their cellular behaviors and metabolic states of probiotic strains under various gut environments. Here, we summarize currently available GEMs of microbial strains with probiotic potentials and propose a knowledge-based framework to evaluate metabolic capabilities on the basis of six probiotic criteria. They include metabolic characteristics, stability, safety, colonization, postbiotics, and interaction with the gut microbiome which can be assessed by in silico approaches. As such, the most suitable strains can be identified to design personalized multi-strain probiotics in the future., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

We systematically reviewed studies to examine changes in women's diets from pregnancy to the postpregnancy period and sought to understand the characteristics of women making these changes. From a search of 4 databases and up to November 2019, 17 studies met our inclusion criteria. They reported changes in various dietary aspects. Mixed findings were reported for changes in energy and micronutrient intakes. Most studies reported significant decreases in fruit and vegetable consumption, diet quality, and adherence to a healthier dietary pattern during the transition from pregnancy to postpregnancy, whereas increases in discretionary food and fat intakes were observed. Women with lower education level, lower income, and/or who worked full-time tended to have poorer dietary behaviors postpregnancy. Further research, with better aligned dietary measurement time points during pregnancy and postpartum and standardization of dietary assessment tools, is needed for future studies to be comparable. The systematic review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews as CRD42020158033., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Xanthomonas oryzae pv. oryzae (Xoo) is a vascular pathogen that causes leaf blight in rice, leading to severe yield losses. Since the usage of chemical control methods has not been very promising for the future disease management, it is of high importance to systematically gain new insights about Xoo virulence and pathogenesis, and devise effective strategies to combat the rice disease. To do this, we reconstructed a genome-scale metabolic model of Xoo (iXOO673) and validated the model predictions using culture experiments. Comparison of the metabolic architecture of Xoo and other plant pathogens indicated that the Entner-Doudoroff pathway is a more common feature in these bacteria than previously thought, while suggesting some of the unique virulence mechanisms related to Xoo metabolism. Subsequent constraint-based flux analysis allowed us to show that Xoo modulates fluxes through gluconeogenesis, glycogen biosynthesis, and degradation pathways, thereby exacerbating the leaf blight in rice exposed to nitrogenous fertilizers, which is remarkably consistent with published experimental literature. Moreover, model-based interrogation of transcriptomic data revealed the metabolic components under the diffusible signal factor regulon that are crucial for virulence and survival in Xoo. Finally, we identified promising antibacterial targets for the control of leaf blight in rice by using gene essentiality analysis., (© 2020 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Conclusions: This update of the Xg blood group system (Johnson NC. XG: The forgotten blood group system. Immunohematology 2011;27:68-71) notes the identification of a cis-regulatory element of both XG and CD99 expression, remarkably by two independent groups during 2018, and confirmed by another in 2019. A single nucleotide change at the XG locus (rs311103) abolishes GATA1 binding and suppresses both XG and CD99. The last blood group system to resist elucidation of its genetic basis was thereby resolved. Soon afterwards, it was discovered that the rare anti-Xga response, mainly seen in men, is produced by individuals primarily carrying a large deletion in the X chromosome that truncates XG and leads to the Xgnull phenotype.

Aim: Diabetes-related nutrition knowledge (DRNK) is essential for the self-care of patients with type 2 diabetes mellitus (T2DM). A specific tool measuring DRNK can help us to understand awareness levels and tailor structured nutrition education programs. Our study aimed to develop a questionnaire to assess DRNK for individuals with T2DM in Singapore., Methods: An expert panel was formed to consolidate in-depth, culturally suitable, and current information on DRNK. A literature review of diabetes self-care knowledge questionnaires was performed to outline the scope of the questionnaire and generate a question pool. User friendliness was tested in the first draft of the questionnaire (n = 21). Then, a second draft was tested for item difficulty, discrimination index, and internal consistency (n = 62). The final draft was examined for construct validity and test-retest reliability (n = 100)., Results: The final questionnaire (four sections: 27 questions) was found to be consistent and reliable. The item difficulty scores of the selected questions ranged from difficult to desirable (2-85). There was fair to good internal consistency (Cronbach's alpha: 0.66, 0.79, 0.56, and 0.78 for Sections 1, 2, 3 and 4, respectively) and construct validity (independent t-test: P < 0.001). Questions in the final questionnaire had an average discrimination index of 0.3 (reasonably good). The questionnaire was revealed to have good test-retest reliability (intraclass correlation: 0.82-0.84)., Conclusions: The DRNK questionnaire is a valid and reliable measure to complement assessment tools measuring self-efficacy/behaviour in individuals with T2DM living in Singapore., (© 2019 Dietitians Association of Australia.)

Maternal obesity during pregnancy has a detrimental impact on offspring renal development and function. This is pertinent to Indigenous Australians as they are twice as likely as non-Indigenous Australians to develop chronic kidney disease (CKD). The aim of this study was to examine whether there was an association between maternal adiposity and fetal kidney growth in late gestation (>28 weeks) and kidney function in infants, <2.5 years of age, from the Gomeroi gaaynggal cohort. Pre-pregnancy body mass index (BMI) was recorded at the first prenatal visit and maternal adiposity indicators (percent body fat and visceral fat area) measured at >28 weeks gestation by bioelectrical impedance analysis. Fetal kidney structure was assessed by ultrasound. Renal function indicators (urinary albumin:creatinine and protein:creatinine) were measured in infants from a spot urine collection from nappies. Multiple linear regression and multi-level mixed effects linear regression models with clustering were used to account for repeated measures of urine. 147 mother-child pairs were examined. Estimated fetal weight (EFW), but not fetal kidney size, was positively associated with maternal adiposity and pre-pregnancy BMI. When adjusted for smoking, combined kidney volume relative to EFW was negatively associated with maternal percentage body fat. Infant kidney function was not influenced by maternal adiposity and pre-pregnancy BMI (n = 84 observations). Current findings show that Indigenous babies born to obese mothers have reduced kidney size relative to EFW. We suggest that these babies are experiencing a degree of glomerular hyperfiltration in utero, and therefore are at risk of developing CKD in later life, especially if their propensity for obesity is maintained. Although no impact on renal function was observed at <2.5 years of age, long-term follow-up of offspring is required to evaluate potential later life impacts., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Evidence from animal models indicates that exposure to an obesogenic or hyperglycemic intrauterine environment adversely impacts offspring kidney development and renal function. However, evidence from human studies has not been evaluated systematically. Therefore, the aim of this systematic review was to synthesize current research in humans that has examined the relationship between gestational obesity and/or diabetes and offspring kidney structure and function. Systematic electronic database searches were conducted of five relevant databases (CINAHL, Cochrane, EMBASE, MEDLINE and Scopus). Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed, and articles screened by two independent reviewers generated nine eligible papers for inclusion. Six studies were assessed as being of 'neutral' quality, two of 'negative' and one 'positive' quality. Observational studies suggest that offspring exposed to a hyperglycemic intrauterine environment are more likely to display markers of renal dysfunction and are at higher risk of end-stage renal disease. There was limited and inconsistent evidence for a link between exposure to an obesogenic intrauterine environment and offspring renal outcomes. Offspring renal outcome measures across studies were diverse, with a large variation in offspring age at follow-up, limiting comparability across studies. The collective current body of evidence suggests that intrauterine exposure to maternal obesity and/or diabetes adversely impacts renal programming in offspring, with an increased risk of kidney disease in adulthood. Further high-quality, longitudinal, prospective cohort studies that measure indicators of offspring renal development and function, including fetal kidney volume and albuminuria, at standardized follow-up time points, are warranted.

Maternal undernutrition during pregnancy is prevalent across the globe, and the origins of many chronic diseases can be traced back to in utero conditions. This systematic review considers the current evidence in animal models regarding the relationship between maternal global nutrient restriction during pregnancy and offspring kidney structure and function. CINAHL, Cochrane, EMBASE, MEDLINE, and Scopus were searched to November 2017. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed, and articles were screened by two independent reviewers. Twenty-eight studies met the inclusion criteria: 16 studies were on rats, 9 on sheep, 2 on baboons, and 1 on goats. The majority of the rat studies had maternal global nutrient restriction during pregnancy at 50% of ad libitum while restriction for sheep and baboon studies ranged from 50% to 75%. Because of the heterogeneity of outcome measures and the large variation in the age of offspring at followup, no meta-analysis was possible. Common outcome measures included kidney weight, nephron number, glomerular size, glomerular filtration rate, and creatinine clearance. To date, there have been no studies assessing kidney function in large animal models. Most studies were rated as having a high or unknown risk of bias. The current body of evidence in animals suggests that exposure to maternal global nutrient restriction during pregnancy has detrimental effects on offspring kidney structure and function, such as lower kidney weight, lower nephron endowment, larger glomerular size, and lower glomerular filtration rate. Further long-term followup of studies in large animal models investigating kidney function through to adulthood are warranted.

Background: The PBDX/XG gene encoding the Xg a blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a-) individuals could not explain the rarity of anti-Xg a makers. We therefore sought to elucidate the molecular basis of the Xg(a-) phenotype in people producing anti-Xg a ., Study Design and Methods: Two genomic DNA (gDNA) and 13 plasma-derived cell-free DNA (cfDNA) samples from anti-Xg a makers were investigated (14 males and one female). PBDX/XG exon sequencing was attempted on one gDNA sample. Polymerase chain reaction assays were developed and bioinformatics used to define a suspected deletion in all samples., Results: Investigation of one gDNA sample revealed a 114-kb deletion (esv2662319) on the X chromosome that spans XG exons 4 through 10 and the downstream GYG2 gene. A 3555-bp fragment bridging this deletion was amplified to confirm its presence. Another deletion-specific polymerase chain reaction of 714 bp enabled identification of esv2662319 in both gDNA samples and eight cfDNA samples while ruling it out in one cfDNA. Males were hemizygous for esv2662319 and the female likely homozygous. Four cfDNA sample results were inconclusive, probably due to poor sample quality. Sanger sequencing recognized the recombination junctions as a heterogeneous LTR6B sequence., Conclusion: We identified a large deletion on the X chromosome, resulting in a true, tissue-wide Xg null phenotype. This deletion was found in 10 of 11 anti-Xg a makers from which DNA could be amplified. One sample remained unexplained, indicating further heterogeneity to be explored., (© 2019 AABB.)

Cancer is a deadly disease and there is an urgent need for the development of effective and safe therapeutic agents to treat it. Snake venom is a complex mixture of bioactive proteins that represents an attractive source of novel and naturally-derived anticancer agents. Malaysia is one of the world's most biodiverse countries and is home to various venomous snake species, including cobras. Naja kaouthia , Naja sumatrana , and Ophiophagus hannah are three of the most common cobra species in Malaysia and are of medical importance. Over the past decades, snake venom has been identified as a potential source of therapeutic agents, including anti-cancer agents. This present review highlights the potential anticancer activity of the venom and purified venom protein of N. kaouthia, N. sumatrana , and O. hannah . In conclusion, this review highlights the important role of the venom from Malaysian cobras as an important resource that researchers can exploit to further investigate its potential in cancer treatment.