Elucidation of toxic effects of 1,2-diacetylbenzene: an in silico study.

PURPOSE: We aimed to explore the metabolite products of 1,2-diacetylbenzene (DAB) and investigate their harmful effects, physicochemical properties, and biological activities, along with those of DAB itself. METHODS: Key approaches included MetaTox, PASS online, ADMESWISS, ADMETlab 2.0, molecular docking, and molecular dynamic simulation to identify metabolites, toxic effects, Lipinski's rule criteria, absorption, distribution, metabolism, and excretion properties, interactions with cytochrome (CYP) 450 isoforms, and the stability of the DAB-cytochrome complex. RESULTS: A total of 13 metabolite products from DAB were identified, involving Phase I reactions (aliphatic hydroxylation, epoxidation, oxidative dehydrogenation, and hydrogenation) and Phase II reactions (oxidative sulfation and methylation). Molecular dynamics and modeling revealed a stable interaction between CYP1A2 and DAB, suggesting the involvement of CYP1A2 in DAB metabolism. All studied compounds adhered to Lipinski's rule, indicating their potential as inducers or activators of toxic mechanisms. The physicochemical parameters and pharmacokinetics of the investigated compounds were consistent with their harmful effects, which included neurotoxic, nephrotoxic, endocrine disruptor, and hepatotoxic consequences due to their high gastrointestinal absorption and ability to cross the blood-brain barrier. Various CYP450 isoforms exhibited different functions, and the compounds were found to act as superoxide dismutase inhibitors, neuropeptide Y2 antagonists, glutaminase inhibitors, and activators of caspases 3 and 8. DAB and its metabolites were also associated with apoptosis, oxidative stress, and neuroendocrine disruption. CONCLUSION: The toxic effects of DAB and its metabolites were predicted in this study. Further research is warranted to explore their effects on other organs, such as the liver and kidneys, and to validate our findings.

Assessing the impact of stricter drink driving policy on alcohol consumption in a population of Hanoi, Vietnam using wastewater analysis.

INTRODUCTION: On 1 January 2020, Vietnam introduced a new law with harsher fines and penalties for driving under the influence of alcohol. Reports of empty beer restaurants following this implementation suggested the new law has the potential to reduce population-level alcohol consumption. This pilot study aims to quantify short-term changes in alcohol consumption levels after the implementation of the new law and assess whether it could lead to a reduction in total alcohol consumption in the population. METHODS: Wastewater samples were collected from two sites along a sewage canal in Hanoi during two periods: Period 1 (15 December 2018 to 14 January 2019) and Period 2 (15 December 2019 to 14 January 2020). Ethyl sulfate, a specific metabolite of alcohol, was quantified to monitor the trend of alcohol consumption. Both interrupted time series and controlled interrupted time series approaches were utilised, with Period 1 and Period 2 serving as the control and intervention periods, respectively. RESULTS: Our analysis indicated that the implementation of the new law did not result in an immediate and significant reduction in alcohol consumption at the population level. Meanwhile, there was no significant difference in alcohol consumption between weekdays and weekends both before and after the implementation of the new law. DISCUSSION AND CONCLUSIONS: Long-term monitoring is needed to assess the impact of stricter DUI policy on alcohol consumption in the urban areas of Vietnam.

Need for an Artificial Intelligence-based Diabetes Care Management System in India and the United States.

Objective: Diabetes mellitus is an important chronic disease that is prevalent around the world. Different countries and diverse cultures use varying approaches to dealing with this chronic condition. Also, with the advancement of computation and automated decision-making, many tools and technologies are now available to patients suffering from this disease. In this work, the investigators attempt to analyze approaches taken towards managing this illness in India and the United States. Methods: In this work, the investigators have used available literature and data to compare the use of artificial intelligence in diabetes management. Findings: The article provides key insights to comparison of diabetes management in terms of the nature of the healthcare system, availability, electronic health records, cultural factors, data privacy, affordability, and other important variables. Interestingly, variables such as quality of electronic health records, and cultural factors are key impediments in implementing an efficiency-driven management system for dealing with this chronic disease. Conclusion: The article adds to the body of knowledge associated with the management of this disease, establishing a critical need for using artificial intelligence in diabetes care management.

Effect of saponins in Panax notoginseng (Burkill) F. H. Chen on the steroid hormone levels in the chronic unpredictable mild stress model of depression in rats.

Recent research has indicated that Panax notoginseng saponins (PNS) extracted from the radix of Panax notoginseng (Burkill) F. H. Chen exert antidepressant effects. This study aimed to assess the antidepressive effects of ginsenoside Rg1 and PNS in a depression model induced by chronic unpredictable mild stress (CUMS). Over a period of three weeks, rats were administered ginsenoside Rg1 at a dose of 30 mg/kg and PNS at dosages ranging from 100 to 200 mg/kg body weight per day. To assess how ginsenoside Rg1 and PNS influence depression-like behaviours in rats, various assessments were conducted, including coat state evaluation, forced swim test, and elevated plus maze test. The levels of cortisol and testosterone in serum samples were analysed using the liquid chromatography-electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) method. LC-ESI-MS/MS method provides precise and accurate results. The lower limit of quantification values for cortisol and testosterone were determined as 100 and 2 pg/mL, respectively. Our data demonstrated that both ginsenoside Rg1 and PNS significantly reversed depression-like behaviour in rats by improving coat condition, reducing immobility time in the forced swim test, and increasing time spent in the open arms of the elevated plus maze test. Furthermore, ginsenoside Rg1 and PNS exhibited a regulatory effect on cortisol and testosterone levels in plasma. These findings suggest that ginsenoside Rg1 and PNS may be potential antidepressants in clinical treatment.

Preventable Deaths Attributable to Second-Hand Smoke in Southeast Asia-Analysis of the Global Burden of Disease Study 2019.

Objectives: In addition to harms caused to individuals who smoke, second-hand smoke (SHS or passive smoke) is an important public health issue. We aim to estimate the extent of preventable deaths due to tobacco and SHS exposure in Southeast Asia. Methods: Data were from the Global Burden of Disease Study 2019. We analysed data from Southeast Asia, including Cambodia, Indonesia, Laos, Malaysia, Maldives, Mauritius, Myanmar, Philippines, Seychelles, Sri Lanka, Thailand, Timor-Leste, and Vietnam. Results: In 2019, there were 728,500 deaths attributable to tobacco in Southeast Asia, with 128,200 deaths attributed to SHS exposure. The leading causes of preventable deaths were ischemic heart disease, stroke, diabetes mellitus, lower respiratory infections, chronic obstructive pulmonary disease, tracheal, bronchus, and lung cancer. Among deaths attributable to tobacco, females had higher proportions of deaths attributable to SHS exposure than males in Southeast Asia. Conclusion: The burden of preventable deaths in a year due to SHS exposure in Southeast Asia is substantial. The implementation and enforcement of smoke-free policies should be prioritized to reduce the disease burden attributed to passive smoking in Southeast Asia.

Harm perceptions across vaping product features: An on-line cross-sectional survey of adults who smoke and/or vape in the United Kingdom.

BACKGROUND AND AIMS: Vaping products are diverse with a wide variety of features, and popular products change rapidly. This study examined the features and types of vaping products that people who smoke and/or vape perceive contribute to the health harms of vaping. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional survey co-designed with adults who smoked/vaped and pre-registered. An on-line survey (November 2022) was used of a convenience sample of adults in the United Kingdom who smoked and/or vaped (n = 494). MEASUREMENTS: As primary outcomes, respondents were asked to select any of 15 vaping product features they perceived might have any effect on the health harms of vaping (for each: selected, not selected). Independent variables were smoking/vaping status (smoke and vape; vape, formerly smoked; vape, never regularly smoked; smoke, do not currently vape); relative vaping harm perceptions [less harmful than smoking (accurate), equally/more harmful than smoking or do not know/refused (other)]. Binary logistic regressions were used to compare outcomes by current vaping/smoking status and relative harm perceptions, adjusting for age and sex. FINDINGS: Most people (54.7%) selected between one and three features. The most frequently selected were nicotine concentration (62.2%) and amount of e-liquid consumed (59.1%), followed by nicotine type (e.g. salt or freebase; 33.0%), source/purchase location (25.3%), flavours (24.7%), temperature to heat e-liquid (21.1%), heat produced by device (20.9%), e-liquid brand (20.9%), amount of emissions (18.6%), device type (e.g. disposable, pod, tank; 17.2%), material of tank (17.0%), power/wattage (13.0%), device brand (8.1%), device size (4.1%) and device weight (2.4%). Higher nicotine concentrations, more e-liquid and salt (versus freebase) nicotine were perceived to confer greater harms. Disposables were perceived as slightly more harmful than reusable devices. There were few differences by current vaping/smoking status and between those with accurate (versus other) harm perceptions of vaping relative to smoking (P > 0.05 for most contrasts, adjusting for age and sex). CONCLUSIONS: Certain features and types of vaping products [higher nicotine concentrations, more e-liquid consumed and salt (versus freebase) nicotine] were perceived to confer greater health harms among a sample of UK adults who smoked and/or vaped. Findings are consistent with pervasive misperceptions that nicotine is a major cause of harm, although e-liquid volume is likely to contribute to harms.

A theoretical study of the oxidation of benzene by manganese oxide clusters: formation of quinone intermediates.

Manganese oxides (MnxOy) have been widely applied in various chemical industrial processes owing to their long lifetime, low cost and high abundance. They have been used as co-reactants for the elimination of volatile organic compounds (VOCs); however, their oxidation mechanism is not clearly established. In this theoretical study, interaction capacities between benzene (C6H6) and MnxOy clusters, which were modeled with MnO2 and Mn2O3 molecules, were investigated by quantum chemical computations using density functional theory (DFT) with the PBE-D3 functional. The interaction capacity between C6H6 and MnxOy was evaluated, and the probing of the initial stage of the C6H6 oxidation at a molecular level offers an in-depth oxidation reaction path. Interaction energies computed in several spin states, along with the analysis of the electron distribution using the quantum theory of atoms in molecules, natural bond orbital and Wiberg bond index techniques as well as local softness values and MO energies of fragments, point out that the interaction between C6H6 and Mn2O3 is stronger than that with MnO2, amounting to -43 and -35 kcal mol-1, respectively, and the metal atom is identified as the primary active site. During the oxide cluster-assisted oxidation, benzene firstly undergoes an oxidation reaction by active oxygen to generate intermediates such as hydroquinone and benzoquinone. The pathway involving p-benzoquinone as the product (noted as PR1) is the most energetically favored one through a transition structure lying at 19 kcal mol-1, below the energy reference of the reactants, leading to an energy barrier significantly lower than that of 36 kcal mol-1 found for the gas phase oxidation reaction with molecular oxygen without the assistance of the oxide clusters. Potential energy profiles illustrating the reaction paths and molecular mechanisms were described in detail.

An in silico investigation of the toxicological effects and biological activities of 3-phenoxybenzoic acid and its metabolite products.

We aimed to elucidate the toxic effects and biological activities of 3-phenoxybenzoic acid (3PBA) and its metabolite products.Numerous in silico methods were used to identify the toxic effects and biological activities of 3PBA, including PASS online, molecular docking, ADMETlab 2.0, ADMESWISS, MetaTox, and molecular dynamic simulation.Ten metabolite products were identified via Phase II reactions (O-glucuronidation, O-sulfation, and methylation).All of the investigated compounds were followed by Lipinski's rule, indicating that they were stimulants or inducers of hazardous processes.Because of their high gastrointestinal absorption and ability to reach the blood-brain barrier, the studied compounds' physicochemical and pharmacokinetic properties matched existing evidence of harmful effects, including haematemesis, reproductive dysfunction, allergic dermatitis, toxic respiration, and neurotoxicity.The studied compounds have been linked to the apoptotic pathway, the reproductivity system, neuroendocrine disruptors, phospholipid-translocating ATPase inhibitors, and JAK2 expression.An O-glucuronidation metabolite product demonstrated higher binding affinity and interaction with CYP2C9, CYP3A4, caspase 3, and caspase 8 than 3PBA and other metabolite products, whereas metabolite products from methylation were predominant and more toxic.Our in silico findings partly meet the 3Rs principle by minimizing animal testing before more study is needed to identify the detrimental effects of 3PBA on other organs (liver, kidneys).Future research directions may involve experimental validation of in silico predictions, elucidation of molecular mechanisms, and exploration of therapeutic interventions.These findings contribute to our understanding of the toxicological profile of 3PBA and its metabolites, which has implications for risk assessment and regulatory decisions.

Key properties & pharmacokinetics of 3PBA & its metabolites were reportedMetabolite products from methylation were predominant and more toxicMain toxics: haematemesis, reproductive dysfunction, toxic respiration, dermatitis.

The underbelly of E-cigarette advertising: regulating online markets on social media platforms.

Australia prohibits the sale of nicotine-vaping products unless prescribed by medical practitioners. Significant policy reforms were announced on the 28th of November 2023 including a ban on single-use disposable vapes with and without nicotine, and the removal of the personal importation scheme. Despite stringent regulations, loopholes exist such that e-cigarette vendors are getting around it, and online markets provide a route to do so. We discuss strategies used by vendors to covertly market e-cigarettes online through social media. In this perspective, we highlight three proposed policies to strengthen social media regulations that may be feasible to implement. Our proposed strategies to regulate e-cigarette product listings on social media involve implementing robust age verification measures, enhancing the system for flagging and reporting prohibited content, and developing a more effective system to identify and flag content related to e-cigarettes.

Development of plant-based whole egg analogs using emulsion technology.

RuBisCO is a plant protein that can be derived from abundant and sustainable natural resources (such as duckweed), which can be used as both an emulsifying and gelling agent. Consequently, it has the potential to formulate emulsion gels that can be used for the development of plant-based replacements of whole eggs. In this study, we investigated the ability of RuBisCO-based emulsion gels to mimic the desirable properties of whole eggs. The emulsion gels contained 12.5 wt% RuBisCO and 10 wt% corn oil to mimic the macronutrient composition of real whole eggs. Initially, an oil-in-water emulsion was formed, which was then heated to convert it into an emulsion gel. The impact of oil droplet diameter (∼15, 1, and 0.2 µm) on the physicochemical properties of the emulsion gels was investigated. The lightness and hardness of the emulsion gels increased as the droplet size decreased, which meant that their appearance and texture could be modified by controlling droplet size. Different concentrations of curcumin (3, 6, and 9 mg/g oil) were incorporated into the emulsions using a pH-driven approach. The curcumin was used as a natural dual functional ingredient (colorant and nutraceutical). The yellow-orange color of curcumin allowed us to match the appearance of raw and cooked whole eggs. This study shows that whole egg analogs can be formulated using plant-based emulsion gels containing natural pigments.

Molecular mechanisms implicated in protein changes in the Alzheimer's disease human hippocampus.

This study aimed to elucidate the specific biochemical pathways linked to changes in proteins in the Alzheimer's disease (AD) human hippocampus. Our data demonstrate a constant rise in the expression of four proteins (VGF, GFAP, HSPB1, and APP) across all eleven studies. Notably, UBC was the most centrally involved and had increased expression in the hippocampus tissue of individuals with AD. Modified proteins in the hippocampal tissue were found to activate the innate immune system and disrupt communication across chemical synapses. Four hub proteins (CD44, APP, ITGB2, and APOE) are connected to amyloid plaques, whereas two hub proteins (RPL24 and RPS23) are related to neurofibrillary tangles (NFTs). The presence of modified proteins was discovered to trigger the activation of microglia and decrease the functioning of ribosomes and mitochondria in the hippocampus. Three significant microRNAs (hsa-miR-106b-5p, hsa-miR-17-5p, and hsa-miR-16-5p) and transcription factors (MYT1L, PIN1, and CSRNP3) have been discovered to improve our understanding of the alterations in proteins within the hippocampal tissues that lead to the progression of AD. These findings establish a path for possible treatments for AD to employ therapeutic strategies that specifically focus on the proteins or processes linked to the illness.

The therapeutic landscape for COVID-19 and post-COVID-19 medications from genetic profiling of the Vietnamese population and a predictive model of drug-drug interaction for comorbid COVID-19 patients.

Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.

Corrigendum to "Financing for HIV/AIDS in the dual transition of epidemics and economy: the 10-year experience of Vietnam" [The Lancet Regional Health - Western Pacific 38 (2023) 100886].

[This corrects the article DOI: 10.1016/j.lanwpc.2023.100886.].

Designing observational studies for credible causal inference in addiction research-Directed acyclic graphs, modified disjunctive cause criterion and target trial emulation.

Randomized controlled trials (RCTs) are considered the gold standard for causal inference. With a sufficient sample size, randomization removes confounding up to the time of randomization and allows the treatment effect to be isolated. However, RCTs may have limited generalizability and transportability and are often not feasible in addiction research due to ethical or logistical constraints. The importance of observational studies from real-world settings has been increasingly recognized in research on health. This paper provides an overview of modern approaches to designing observational studies that enable causal inference. It illustrates three key techniques, Directed Acyclic Graphs (DAGs), modified Disjunctive Cause Criterion and Target Trial Emulation, and discusses the strengths and limitations of their applications.

A study of genetic variants associated with skin traits in the Vietnamese population.

BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.

Uncovering epigenetic and transcriptional regulation of growth in Douglas-fir: identification of differential methylation regions in mega-sized introns.

Tree growth performance can be partly explained by genetics, while a large proportion of growth variation is thought to be controlled by environmental factors. However, to what extent DNA methylation, a stable epigenetic modification, contributes to phenotypic plasticity in the growth performance of long-lived trees remains unclear. In this study, a comparative analysis of targeted DNA genotyping, DNA methylation and mRNAseq profiling for needles of 44-year-old Douglas-fir trees (Pseudotsuga menziesii (Mirb.) Franco) having contrasting growth characteristics was performed. In total, we identified 195 differentially expressed genes (DEGs) and 115 differentially methylated loci (DML) that are associated with genes involved in fitness-related processes such as growth, stress management, plant development and energy resources. Interestingly, all four intronic DML were identified in mega-sized (between 100 and 180 kbp in length) and highly expressed genes, suggesting specialized regulation mechanisms of these long intron genes in gymnosperms. DNA repetitive sequences mainly comprising long-terminal repeats of retroelements are involved in growth-associated DNA methylation regulation (both hyper- and hypomethylation) of 99 DML (86.1% of total DML). Furthermore, nearly 14% of the DML was not tagged by single nucleotide polymorphisms, suggesting a unique contribution of the epigenetic variation in tree growth.

Nucleic acid-induced inflammation on hematopoietic stem cells.

Hematopoiesis, the process of generating blood cells, starts during development with the primitive, pro-definitive, and definitive hematopoietic waves. The first two waves will generate erythrocytes and myeloid cells, although the definitive wave will give rise to hematopoietic stem cells (HSCs) that are multipotent and can produce most of the blood cells in an adult. Although HSCs are highly proliferative during development, during adulthood they remain quiescent in the bone marrow. Inflammatory signaling in the form of interferons, interleukins, tumor necrosis factors, and others is well-established to influence both developmental and adult hematopoiesis. Here we discuss the role of specific inflammatory pathways that are induced by sensing nucleic acids. We discuss the role of RNA-sensing members of the Toll-like, Rig-I-like, nucleotide-binding oligomerization domain (NOD)-like, and AIM2-like protein kinase receptors and the DNA-sensing receptors, DEAD-Box helicase 41 (DDX41) and cGAS. The main downstream pathways of these receptors are discussed, as well as their influence on developmental and adult hematopoiesis, including hematopoietic pathologies.

A rapid and reference-free imputation method for low-cost genotyping platforms.

Most current genotype imputation methods are reference-based, which posed several challenges to users, such as high computational costs and reference panel inaccessibility. Thus, deep learning models are expected to create reference-free imputation methods performing with higher accuracy and shortening the running time. We proposed a imputation method using recurrent neural networks integrating with an additional discriminator network, namely GRUD. This method was applied to datasets from genotyping chips and Low-Pass Whole Genome Sequencing (LP-WGS) with the reference panels from The 1000 Genomes Project (1KGP) phase 3, the dataset of 4810 Singaporeans (SG10K), and The 1000 Vietnamese Genome Project (VN1K). Our model performed more accurately than other existing methods on multiple datasets, especially with common variants with large minor allele frequency, and shrank running time and memory usage. In summary, these results indicated that GRUD can be implemented in genomic analyses to improve the accuracy and running-time of genotype imputation.

Preference and willingness to pay for reproductive health services among adults in Urban-Rural transition settings of a developing country: evidence from a cross-sectional study in a rural district of Hanoi, Vietnam.

BACKGROUND: Since the introduction of fee-for-service models in public hospitals and the legalization of private health services in Vietnam in 1989, the price of reproductive health services has risen. These changes have exacerbated inequities in accessing reproductive health services. This study examines potential disparities in willingness to pay for reproductive health services among adults in a rural district of Hanoi. METHODS: A cross-sectional study was conducted at 9 communes in Thanh Oai district, a rural district of Hanoi, Vietnam, in July 2019. Face-to-face interviews were conducted using a structured questionnaire to collect self-reported data. The contingent valuation was used to examine willingness to pay for reproductive health services with a starting price of 2 million VND (~ US$86.2, July 2019 exchange rate), which is the average price of all RHS in public facilities in Vietnam. Multiple Logistic regression and Multiple Interval regression models were used to identify factors associated with willingness to pay and the amount that people were willing to pay for reproductive health services. RESULTS: Among 883 participants, this study found 59.1% of them willing to pay for reproductive health services at an average maximum amount of US$36.2, significantly less than the current average price of US$86.2. Occupation, number of sex partners, perception towards the necessity of reproductive health services, and prior use of reproductive health services were found to significantly influence willingness to pay for reproductive health services, while age, income level, gender, occupation, perception towards the necessity of reproductive health services and prior use of reproductive health services were reportedly correlated with the amount participants were willing to pay for reproductive health services. CONCLUSION: Lower willingness to pay for reproductive health services compared to the current prices (US$36.2 vs. US$86.2) is likely related to an overall low awareness of the necessity of reproductive health services, and future education campaigns should specifically target those from lower-income backgrounds. Financial subsidization should also be provided, especially for those from the low-income group, to ensure equitable access to reproductive health services. Given the heterogeneity of reproductive health services, further studies should examine the willingness to pay for each type of service independently.

Pathogenicity Prediction of GABAA Receptor Missense Variants.

Variants in the genes encoding the subunits of gamma-aminobutyric acid type A (GABAA) receptors are associated with epilepsy. To date, over 1000 clinical variants have been identified in these genes. However, the majority of these variants lack functional studies and their clinical significance is uncertain although accumulating evidence indicates that proteostasis deficiency is the major disease-causing mechanism for GABAA receptor variants. Here, we apply two state-of-the-art modeling tools, namely AlphaMissense, which uses an artificial intelligence-based approach based on AlphaFold structures, and Rhapsody, which integrates sequence evolution and known structure-based data, to predict the pathogenicity of saturating missense variants in genes that encode the major subunits of GABAA receptors in the central nervous system, including GABRA1, GABRB2, GABRB3, and GABRG2. Our results demonstrate that the predicted pathogenicity correlates well between AlphaMissense and Rhapsody although AlphaMissense tends to generate higher pathogenic probability. Furthermore, almost all annotated pathogenic variants in the ClinVar clinical database are successfully identified from the prediction, whereas uncertain variants from ClinVar partially due to the lack of experimental data are differentiated into different pathogenicity groups. The pathogenicity prediction of GABAA receptor missense variants provides a resource to the community as well as guidance for future experimental and clinical investigations.