Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography.

Many COVID-19 patients infected by SARS-CoV-2 virus develop pneumonia (called novel coronavirus pneumonia, NCP) and rapidly progress to respiratory failure. However, rapid diagnosis and identification of high-risk patients for early intervention are challenging. Using a large computed tomography (CT) database from 3,777 patients, we developed an AI system that can diagnose NCP and differentiate it from other common pneumonia and normal controls. The AI system can assist radiologists and physicians in performing a quick diagnosis especially when the health system is overloaded. Significantly, our AI system identified important clinical markers that correlated with the NCP lesion properties. Together with the clinical data, our AI system was able to provide accurate clinical prognosis that can aid clinicians to consider appropriate early clinical management and allocate resources appropriately. We have made this AI system available globally to assist the clinicians to combat COVID-19.

Ultrastrong spinodoid alloys enabled by electrochemical dealloying and refilling.

We present an extreme case of composition-modulated nanomaterial formed by selective etching (dealloying) and electrochemical refilling. The product is a coarse-grain polycrystal consisting of two interwoven nanophases, with identical crystal structures and a cube-on-cube relationship, separated by smoothly curved semicoherent interfaces with high-density misfit dislocations. This material resembles spinodal alloys structurally, but its synthesis and composition modulation are spinodal-independent. Our Cu/Au "spinodoid" alloy demonstrates superior mechanical properties such as near-theoretical strength and single-phase-like behavior, owing to its fine composition modulation, large-scale coherence of crystal lattice, and smoothly shaped three-dimensional (3D) interface morphology. As a unique extension of spinodal alloy, the spinodoid alloy reported here reveals a number of possibilities to modulate the material's structure and composition down to the nanoscale, such that further improved properties unmatchable by conventional materials can be achieved.

Multiple Origins and Genomic Basis of Complex Traits in Sighthounds.

Sighthounds, a distinctive group of hounds comprising numerous breeds, have their origins rooted in ancient artificial selection of dogs. In this study, we performed genome sequencing for 123 sighthounds, including one breed from Africa, six breeds from Europe, two breeds from Russia, and four breeds and 12 village dogs from the Middle East. We gathered public genome data of five sighthounds and 98 other dogs as well as 31 gray wolves to pinpoint the origin and genes influencing the morphology of the sighthound genome. Population genomic analysis suggested that sighthounds originated from native dogs independently and were comprehensively admixed among breeds, supporting the multiple origins hypothesis of sighthounds. An additional 67 published ancient wolf genomes were added for gene flow detection. Results showed dramatic admixture of ancient wolves in African sighthounds, even more than with modern wolves. Whole-genome scan analysis identified 17 positively selected genes (PSGs) in the African population, 27 PSGs in the European population, and 54 PSGs in the Middle Eastern population. None of the PSGs overlapped in the three populations. Pooled PSGs of the three populations were significantly enriched in "regulation of release of sequestered calcium ion into cytosol" (gene ontology: 0051279), which is related to blood circulation and heart contraction. In addition, ESR1, JAK2, ADRB1, PRKCE, and CAMK2D were under positive selection in all three selected groups. This suggests that different PSGs in the same pathway contributed to the similar phenotype of sighthounds. We identified an ESR1 mutation (chr1: g.42,177,149 T > C) in the transcription factor (TF) binding site of Stat5a and a JAK2 mutation (chr1: g.93,277,007 T > A) in the TF binding site of Sox5. Functional experiments confirmed that the ESR1 and JAK2 mutation reduced their expression. Our results provide new insights into the domestication history and genomic basis of sighthounds.

An OBP gene highly expressed in non-chemosensory tissues affects the phototaxis and reproduction of Spodoptera frugiperda.

Insect odorant binding proteins (OBPs) were initially regarded as carriers of the odorants involved in chemosensation. However, it had been observed that a growing number of OBP genes exhibited broad expression patterns beyond chemosensory tissues. Here, an OBP gene (OBP31) was found to be highly expressed in the larval ventral nerve cord, adult brain and male reproductive organ of Spodoptera frugiperda. An OBP31 knockout strain (OBP31-/- ) was generated by CRISPR/Cas9 mutagenesis. For OBP31-/- , the larvae needed longer time to pupate, but there was no difference in the pupal weight between OBP31-/- and wild type (WT). OBP31-/- larvae showed stronger phototaxis than the WT larvae, indicating the importance of OBP31 in light perception. For mating rhythm of adults, OBP31-/- moths displayed an earlier second mating peak. In the cross-pairing of OBP31-/- and WT moths, the mating duration was longer, and hatchability was lower in OBP31-/- group and OBP31+/- ♂ group than that in the WT group. These results suggested that OBP31 played a vital role in larval light perception and male reproductive process and could provide valuable insights into understanding the biological functions of OBPs that were not specific in chemosensory tissues.

Insulin and circadian rhythm genes of the Nile rat (Arvicanthis niloticus) are conserved and orthologous to those in the rat, mouse and human.

The African grass or Nile rat (NR) (Arvicanthis niloticus) is a herbivorous diurnal rodent which is used as a biological model for research on type 2 diabetes mellitus (T2DM) and the circadian rhythm. Similar to humans, male NRs develop T2DM with high-carbohydrate diets. The NR thus provides a unique opportunity to identify the nutritional and underlying genetic factors that characterise human T2DM, as well as the effects of potential anti-diabetic phytochemicals such as Water-Soluble Palm Fruit Extract. Whole genome sequencing (WGS) could help identify possible genetic causes why NRs spontaneously develop T2DM in captivity. In this study, we performed WGS on a hepatic deoxyribonucleic acid (DNA) sample isolated from a male NR using PacBio high-fidelity long-read sequencing. The WGS data obtained were then de novo assembled and annotated using PacBio HiFi isoform sequencing (Iso-Seq) data as well as previous Illumina RNA sequencing (RNA-Seq) data. Genes related to insulin and circadian rhythm pathways were present in the NR genome, similar to orthologues in the rat, mouse and human genomes. T2DM development in the NR is thus most likely not attributable to structural differences in these genes when compared to other biological models. Further studies are warranted to gain additional insights on the genetic-environmental factors which underlie the genetic permissiveness of NRs to develop T2DM.

A systematic review of the association between environmental risk factors and the development of irritable bowel syndrome.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with roots in genetic, immune, psychological, and dietary factors. Recently, the potential correlation between environmental exposures, such as air pollution, and IBS has gained attention. This review aimed to systematically examine existing studies on environmental factors associated with IBS, elucidating this interplay and guiding future research. METHODS: A literature search was conducted in Medline, EMBASE, Scopus, and Cochrane databases from database inception to October 10, 2023, using the keywords "Irritable Bowel" or IBS or "Irritable Colon" or "Mucous Colitis" or "Spastic Colitis" or "Spastic Colon" AND "environment* exposure*". Studies were included if they were original, published in English, described defined environmental exposure(s), and had documented diagnosis of IBS. For the purposes of this review, articles reporting physical (e.g. radiation and climate change), biological (e.g. bacteria and viruses), and chemical (e.g. harmful gases) exposures were included while psychological and dietary factors, which have been reviewed in detail elsewhere, are outside of the scope. RESULTS: A total of seven studies focusing on air quality, microbial exposure, and other environmental factors were reviewed. Studies highlighted a potential association between air pollutants and increased IBS incidence. Microbial exposure, post-natural disaster or due to poor sanitation, was linked to IBS development and gut dysbiosis. Other exposures, such as early pet ownership, were also associated with IBS risk. CONCLUSION: Existing research demonstrates an epidemiologic relationship between environmental exposures and the development of IBS. Further research is needed to understand these associations.

Constructing mesoporous biochar derived from waste carton: Improving multi-site adsorption of dye wastewater and investigating mechanism.

The development of cost-efficient biochar adsorbent with a simple preparation method is essential to constructing efficient wastewater treatment system. Here, a low-cost waste carton biochar (WCB) prepared by a simple two-step carbonization was applied in efficiently removing Rhodamine B (RhB) in aqueous environment. The maximum ability of WCB for RhB adsorption was 222 mg/g, 6 and 10 times higher than both of rice straw biochar (RSB) and broadbean shell biochar (BSB), respectively. It was mainly ascribed to the mesopore structure (3.0-20.4 nm) of WCB possessing more spatial sites compared to RSB (2.2 nm) and BSB (2.4 nm) for RhB (1.4 nm✕1.1 nm✕0.6 nm) adsorption. Furthermore, external mass transfer (EMT) controlled mass transfer resistance (MTR) of the RhB sorption process by WCB which was fitted with the Langmuir model well. Meanwhile, the adsorption process was dominated by physisorption through van der Waals forces and π-π interactions. A mixture of three dyes in river water was well removed by using WCB. This work provides a straightforward method of preparing mesoporous biochar derived from waste carton with high-adsorption capacity for dye wastewater treatment.

The longitudinal dispositions of people diagnosed with adjustment or severe stress disorders.

BACKGROUND: Adjustment and stress-related disorders are prevalent among psychiatric service users. Despite their prevalence, little is known about their prognosis. To reduce that gap, the present article documents the service use and diagnostic outcomes of people with adjustment or stress-related disorders presenting at Singapore's largest psychiatric emergency department. METHODS: Administrative data from 2014 to 2021 was retrieved to follow a group of 683 service users whose first-ever psychiatric presentation in 2014 warranted a diagnosis of adjustment or stress-related disorder. People were grouped a priori depending on whether different diagnoses were recorded within 7 days, 9 months, after 9 months or not at all. Survival curves characterized conversion to other diagnoses and engagement with healthcare services. Service use outcomes include the number of hospitalizations, outpatient appointments, emergency department visits, and prescriptions. RESULTS: Sixty-one percent (n = 417) never received another diagnosis over the 8-year period. This group used emergency services most and received the most pharmacotherapy shortly after their first visit. Of those who received another diagnosis, depression, personality disorders, and psychotic disorders were the most common. Those who received another diagnosis within 7 days (n = 70, 10%) received it on their first day of hospitalization (IQR 1-1), making the most use of inpatient services. The group who received another diagnosis within 9 months (n = 105, 15%) did so after 42 days (IQR 26-84) and had the highest relative number of deaths. Those who received another diagnosis after 9 months (n = 91, 13%) did so after 1,134 days (IQR 613-1,823) and had the longest period of engagement but made the least use of any psychiatric service, potentially suggesting a group whose early index diagnosis heralded vulnerability to future disorders. CONCLUSIONS: A large group of service users with acute stress or adjustment disorders will likely never be given another psychiatric diagnosis and appear to disengage following an initial period of high-intensity service use. The group that received a different diagnosis after the 9-month mark had prolonged contact with services but low intensity of service use and may represent a target for preventative intervention to help them improve their stress-managing skills and avoid developing other disorders.

Experimental and simulation investigation of stereo-DIC via a deep learning algorithm based on initial speckle positioning technology.

For the deep-learning-based stereo-digital image correlation technique, the initial speckle position is crucial as it influences the accuracy of the generated dataset and deformation fields. To ensure measurement accuracy, an optimized extrinsic parameter estimation algorithm is proposed in this study to determine the rotation and translation matrix of the plane in which the speckle is located between the world coordinate system and the left camera coordinate system. First, the accuracy of different extrinsic parameter estimation algorithms was studied by simulations. Subsequently, the dataset of stereo speckle images was generated using the optimized extrinsic parameters. Finally, the improved dual-branch CNN deconvolution architecture was proposed to output displacements and strains simultaneously. Simulation results indicate that DAS-Net exhibits enhanced expressive capabilities, as evidenced by a reduction in displacement errors compared to previous research. The experimental results reveal that the mean absolute percentage error between the stereo-DIC results and the generated dataset is less than 2%, suggesting that the initial speckle positioning technology effectively minimizes the discrepancy between the images in the dataset and those obtained experimentally. Furthermore, the DAS-Net algorithm accurately measures the displacement and strain fields as well as their morphological characteristics.

Comparative Transcriptomics of the Entomopathogenic Fungus Beauveria bassiana Grown on Aerial Surface and in Liquid Environment.

Beauveria bassiana, the causative agent of arthropod, proliferates in the host hemolymph (liquid environment) and shits to saprotrophic growth on the host cadaver (aerial surface). In this study, we used transcriptomic analysis to compare the gene expression modes between these two growth phases. Of 10,366 total predicted genes in B. bassiana, 10,026 and 9985 genes were expressed in aerial (AM) and submerged (SM) mycelia, respectively, with 9853 genes overlapped. Comparative analysis between two transcriptomes indicated that there were 1041 up-regulated genes in AM library when compared with SM library, and 1995 genes were down-regulated, in particular, there were 7085 genes without significant change in expression between two transcriptomes. Furthermore, of 25 amidase genes (AMD), BbAMD5 has high expression level in both transcriptomes, and its protein product was associated with cell wall in aerial and submerged mycelia. Disruption of BbAMD5 significantly reduced mycelial hydrophobicity, hydrophobin translocation, and conidiation on aerial plate. Functional analysis also indicated that BbAmd5 was involved in B. bassiana blastospore formation in broth, but dispensable for fungal virulence. This study revealed the high similarity in global expression mode between mycelia grown under two cultivation conditions.

Y chromosome polymorphisms contribute to an increased risk of non-obstructive azoospermia: a retrospective study of 32,055 Chinese men.

PURPOSE: To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes. METHODS: The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes. RESULTS: The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528). CONCLUSIONS: Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes.

Optimization of the Zhou Tian Formula extraction technology based on AHP-CRITIC method and analysis of transfer efficiency of key components based on HPLC fingerprinting.

INTRODUCTION: Zhou Tian Formula (ZTF) is an antidepressant traditional Chinese medicine utilized widely in clinical settings for the treatment of patients with depression. However, shortcomings persist in its extraction technology and quality control. OBJECTIVE: This study aimed to propose a methodology for ZTF extraction technology based on the analytic hierarchy process (AHP)-criteria importance through intercriteria correlation (CRITIC) method and to establish a quality control framework for the efficient transfer of index components. METHOD: Firstly, we analyzed the chemical components of ZTF and determined the optimal extraction technology. Secondly, we calculated the transfer efficiency of the index components during the conversion of water decoction to extract powder and subsequently to granules. Thirdly, we established HPLC fingerprints for 15 batches of ZTF water decoction, extract powder, and granules. We employed SIMCA software to analyze the chemicals responsible for variations in quality among different batches of ZTF granules. RESULTS: We determined the optimal extraction process. The average transfer efficiency of ferulic acid, puerarin, mirificin, isoferulic acid, and calycosin during the conversion of water decoction to extract powder and subsequently to granules exceeded 41%. The HPLC fingerprints of ZTF exhibited a similarity exceeding 0.890. Variable importance in projection values indicated that calycosin, ferulic acid, and puerarin were the primary contributors to quality variations. CONCLUSIONS: The AHP-CRITIC method, coupled with an orthogonal array design, could be used for exploring extraction technology. In addition, the rules governing the transfer of index components from water decoction to extract powder, and subsequently to granules, could be applied for the evaluation and quality assessment of ZTF.

The Genetic Echo of the Tarim Mummies in Modern Central Asians.

The diversity of Central Asians has been shaped by multiple migrations and cultural diffusion. Although ancient DNA studies have revealed the demographic changes of the Central Asian since the Bronze Age, the contribution of the ancient populations to the modern Central Asian remains opaque. Herein, we performed high-coverage sequencing of 131 whole genomes of Indo-European-speaking Tajik and Turkic-speaking Kyrgyz populations to explore their genomic diversity and admixture history. By integrating the ancient DNA data, we revealed more details of the origins and admixture history of Central Asians. We found that the major ancestry of present-day Tajik populations can be traced back to the admixture of the Bronze Age Bactria-Margiana Archaeological Complex and Andronovo-related populations. Highland Tajik populations further received additional gene flow from the Tarim mummies, an isolated ancient North Eurasian-related population. The West Eurasian ancestry of Kyrgyz is mainly derived from Historical Era populations in Xinjiang of China. Furthermore, the recent admixture signals detected in both Tajik and Kyrgyz are ascribed to the expansions of Eastern Steppe nomadic pastoralists during the Historical Era.

Chemodivergent Tandem Radical Cyclization of Alkene-Substituted Quinazolinones: Rapid Access to Mono- and Di-Alkylated Ring-Fused Quinazolinones.

Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.

State-of-the-art review of theabrownins: from preparation, structural characterization to health-promoting benefits.

As far as health benefit is concerned, dark tea is one of the best beverages in the world. Theabrownins are the major ingredient contributing to the health benefits of dark tea and known as "the soft gold in dark tea." A growing body of evidence indicated that theabrownins are macromolecular pigments with reddish-brown color and mellow taste, and mainly derived from the oxidative polymerization of tea polyphenols. Theabrownins are the main active ingredients in dark tea which brings multiple health-promoting effects in modulating lipid metabolism, reducing body weight gain, attenuating diabetes, mitigating NAFLD, scavenging ROS, and preventing tumors. More importantly, it's their substantial generation in microbial fermentation that endows dark tea with much stronger hypolipidemic effect compared with other types of tea. This review firstly summarizes the most recent findings on the preparation, structural characteristics, and health-promoting effects of theabrownins, emphasizing the underlying molecular mechanism, especially the different mechanisms behind the effect of theabrownins-mediated gut microbiota on the host's multiple health-promoting benefits. Furthermore, this review points out the main limitations of current research and potential future research directions, hoping to provide updated scientific evidence for their better theoretical research and industrial utilization.

Recent advances in the utilization of tea active ingredients to regulate sleep through neuroendocrine pathway, immune system and intestinal microbiota.

Sleep disorders have received widespread attention nowadays, which have been promoted by the accelerated pace of life, unhealthy diets and lack of exercise in modern society. The chemical medications to improve sleep has shown serious side effects and risks with high costs. Therefore, it is urgent to develop efficient nutraceuticals from natural sources to ensure sleep quality as a sustainable strategy. As the second most consumed beverage worldwide, the health-promoting effects of tea have long been widely recognized. However, the modulatory effect of teas on sleep disorders has received much less attention. Tea contains various natural sleep-modulating active ingredients such as L-theanine (LTA), caffeine, tea polyphenols (TPP), tea pigments, tea polysaccharides (TPS) and γ-aminobutyric acid (GABA). This review focuses on the potential influence and main regulating mechanisms of different tea active ingredients on sleep, including being absorbed by the small intestine and then cross the blood-brain barrier to act on neurons in the brain as neurotransmitters, manipulating the immune system and further affect sleep-wake cycle by regulating the levels of cytokines, and controlling the gut microbes to maintain the homeostasis of circadian rhythm. Current research progress and limitations are summarized and several future development directions are also proposed. This review hopes to provide new insights into the future elucidation of the sleep-regulating mechanisms of different teas and their natural active ingredients and the development of tea-based functional foods for alleviating sleep disorders. HighlightsNatural sleep-modulating active ingredients in tea have been summarized.Influences of drinking tea or tea active ingredients on sleep are reviewed.Three main regulating mechanisms of tea active ingredients on sleep are explained.The associations among nervous system, immune system and intestinal microbiota are investigated.The potential of developing delivery carriers for tea active ingredients is proposed.

Green preparation, safety control and intelligent processing of high-quality tea extract.

Tea contains a variety of bioactive components, including catechins, amino acids, tea pigments, caffeine and tea polysaccharides, which exhibit multiple biological activities. These functional components in tea provide a variety of unique flavors, such as bitterness, astringency, sourness, sweetness and umami, which meet the demand of people for natural plant drinks with health benefits and pleasant flavor. Meanwhile, the traditional process of tea plantation, manufacturing and circulation are often accompanied by the safety problems of pesticide residue, heavy metal, organic solvents and other exogenous risks. High-quality tea extract refers to the special tea extract obtained by enriching the specific components of tea. Through green and efficient extraction technologies, diversed high-quality tea extracts such as high-fragrance and high-amino acid tea extracts, low-caffeine and high-catechin tea extracts, high-bioavailability and high-theaflavin tea extracts, high-antioxidant and high-tea polysaccharide tea extracts, high-umami-taste and low-bitter and astringent taste tea extracts are produced. Furthermore, rapid detection, green control and intelligent processing are applied to monitor the quality of tea in real-time, which guarantee the stability and safety of high-quality tea extracts with enhanced efficiency. These emerging technologies will realize the functionalization and specialization of high-quality tea extracts, and promote the sustainable development of tea industry.

Main high-quality tea extracts and their preparation methods were introduced.Potential pollutants in the processing of tea extracts and their detection methods were proposed.Emerging intelligent processing technologies of tea extract were summarized.The applications of high-quality tea extracts in food industry were explored.Future trends of tea extracts and relevant suggestions were presented.

Anammox-Mediated Hydroxyapatite Granules: Physicochemical Properties, 3D Hierarchy, and Biofilm Thickness.

Biomineralization inspired the development of simultaneous biological transformations and chemical precipitation for simultaneous nitrogen removal and phosphorus recovery from wastewater, which could compensate for the incapacity of phosphorus management in the new biological route of anaerobic ammonium oxidation (anammox). In this study, we strengthened anammox-mediated biomineralization by long-term feeding of concentrated N, P, and Ca substrates, and a self-assembled matrix of anammox bacteria and hydroxyapatite (HAP) was fabricated in a granular shape, defined as HAP-anammox granules. HAP was identified as the dominant mineral using elemental analysis, X-ray diffraction, and Raman spectroscopy. The intensive precipitation of HAP resulted in a higher inorganic fraction and substantially improved settleability of anammox biomass, which facilitated HAP precipitation by acting as nucleation and metabolically elevated pH. By using X-ray microcomputed tomography, we visually represented the hybrid texture of interwoven HAP pellets and biomass, the core-shell layered architecture of different-sized HAP-anammox granules, and their homogeneously regulated thickness of the outer biofilm (from 118 to 635 µm). This unique architecture endows HAP-anammox granules with outstanding settleability, active biofilm, and tightly bonded biofilm with the carrier, which may explain the excellent performance of these HAP-anammox granules under various challenging operational conditions in previous studies.

The effectiveness of epilepsy educational intervention using computer game-based epilepsy educational program (Epigame) among Malaysian children with epilepsy: A prospective cohort study.

BACKGROUND: A computer game-based epilepsy educational programme (Epigame) can potentially improve the awareness, knowledge and attitude (AKA) and quality of life (QOL) of children with epilepsy (CWE). Our study among Malaysian CWE aimed to assess the: i) baseline level of epilepsy AKA and potential characteristics associated with poor levels of AKA, ii) effectiveness of Epigame in improving AKA and QOL of CWE. METHOD: Prospective cohort study on CWE age 7-18 years old with no comorbidities. Epilepsy education was delivered using Epigame. CWE completed AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), 3 months (TP3) after provision of Epigame. Child self-report Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL-25) questionnaire was completed at TP1 and TP3. RESULTS: Total of 106 CWE participated in this study (mean age of 13.3 years). Baseline (TP1) AKA was rated "very low to moderate" for awareness domain in 95.3 %, "very low to moderate" for knowledge domain in 67 %, "negative to indifferent" for attitude domain in 54.7 %, and "very poor to moderate' for total AKA score domain in 84 %. "Positive to very positive" for child attitude domain was significantly associated with parents with "positive to very positive" for attitude domain (OR 10.6, 95 % CI 3.23-34.66). "Good to excellent" for total child AKA domain was significantly associated with parents with "Good to excellent" for total AKA domain (OR 5.2, 95 % CI 1.16-15.02) and with < 2 antiseizure medication (OR 5.0, 95 % CI 1.34-18.98). The scores in the knowledge, attitude and total AKA score domains improved significantly after the introduction of Epigame at TP3. There were no significant improvements in the CHEQOL-25 scores over time except for the "Quest for Normality" subscale score (mean of score difference between TP1 and TP3 = 1.0, 95 % CI 0.19-1.81). CONCLUSION: Majority of Malaysian CWE had low levels of epilepsy AKA, particularly among parents with "negative to indifferent" for attitude domain, parents with "very poor to moderate" for total AKA domain and on polytherapy. Introduction of Epigame was effective in improving scores of the knowledge, attitude and total AKA domains, and the QOL "Quest for Normality" domain of the CHEQOL-25.