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Hue Thi Mai,1 Giang Minh Le,1,2 Bach Xuan Tran,1,3,4 Ha Ngoc Do,5 Carl A Latkin,3 Luong Thanh Nguyen,6 Thao Phuong Thi Thai,7,8 Huong Thi Le,9 Anh Toan Ngo,10 Cuong Tat Nguyen,11 Cyrus SH Ho,12 Roger CM Ho13 1Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam; 2Center for Research and Training on HIV/AIDS (CREATA), Hanoi Medical University, Hanoi, Vietnam; 3Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 4Vietnam Young Physician Association, Hanoi, Vietnam; 5Youth Research Institute, Vietnam (YRI)-Ho Chi Minh Communist Youth Union, Hanoi, Vietnam; 6Center of Excellence in Evidence-based Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam; 7Department of General Planning, Friendship Hospital, Hanoi, Vietnam; 8Department of Cardiology, Friendship Hospital, Hanoi, Vietnam; 9Vietnam Administration of HIV/AIDS Control, Hanoi, Vietnam; 10National Hospital of Obstetrics and Gynecology, Hanoi, Vietnam; 11Institute for Global Health Innovations, Duy Tan University, Da Nang, Vietnam; 12Department of Psychological Medicine, National University Hospital, Singapore, Singapore; 13Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Purpose: This study aimed to assess the antiretroviral therapy (ART) compliance among patients with HIV/AIDS and its associated factors in the context of universal ART initiation in Vietnam. Patients and methods: A cross-sectional survey was conducted in five ART clinics located in three provinces, such as Hanoi, Thanh Hoa, and Lao Cai, from July to September 2017. Overall, adherence to ART in the last month was measured using a 100-point Visual Analog Scale (VAS). Besides, information about forgetting doses in the last 4 days and delaying taking pills in the last 7 days was also reported. Results: Among 482 patients, the suboptimal adherence rate was 54.5%. Noncurrent smoking (coefficient =4.19, 95% CI 0.42–7.97), higher baseline CD4 count (coefficient =4.35, 95% CI 0.58–8.13), and no traveling difficulties (coefficient =6.17, 95% CI 2.27–10.06) were predictors of higher VAS adherence score. Suboptimal adherence was associated with mountainous residence (OR =5.34, 95% CI 2.81–10.16). Female respondents were less likely to delay taking pills in the last 7 days (OR =0.19, 95% CI 0.07–0.52). Conclusion: Our study embraced early ART initiation in Vietnam; however, this approach should be parallel with appropriate resource allocation and service delivery. Keywords: HIV/AIDS, antiretroviral therapy, ART adherence, Visual Analog Scale, VAS

Agonists targeting α 2 -adrenergic receptors (ARs) are used to treat diverse conditions, including hypertension, attention-deficit/hyperactivity disorder, pain, panic disorders, opioid and alcohol withdrawal symptoms, and cigarette cravings. These receptors transduce signals through heterotrimeric Gi proteins. Here, we elucidated cryo-EM structures that depict α 2A -AR in complex with Gi proteins, along with the endogenous agonist epinephrine or the synthetic agonist dexmedetomidine. Molecular dynamics simulations and functional studies reinforce the results of the structural revelations. Our investigation revealed that epinephrine exhibits different conformations when engaging with α-ARs and β-ARs. Furthermore, α 2A -AR and β 1 -AR (primarily coupled to Gs, with secondary associations to Gi) were compared and found to exhibit different interactions with Gi proteins. Notably, the stability of the epinephrine-α 2A -AR-Gi complex is greater than that of the dexmedetomidine-α 2A -AR-Gi complex. These findings substantiate and improve our knowledge on the intricate signaling mechanisms orchestrated by ARs and concurrently shed light on the regulation of α-ARs and β-ARs by epinephrine., (© 2024. The Author(s).)

A fundamental understanding of how HIV-1 envelope (Env) protein facilitates fusion is still lacking. The HIV-1 fusion peptide, consisting of 15 to 22 residues, is the N-terminus of the gp41 subunit of the Env protein. Further, this peptide, a promising vaccine candidate, initiates viral entry into target cells by inserting and anchoring into human immune cells. The influence of membrane lipid reorganization and the conformational changes of the fusion peptide during the membrane insertion and anchoring processes, which can significantly affect HIV-1 cell entry, remains largely unexplored due to the limitations of experimental measurements. In this work, we investigate the insertion of the fusion peptide into an immune cell membrane mimic through multiscale molecular dynamics simulations. We mimic the native T-cell by constructing a 9-lipid asymmetric membrane, along with geometrical restraints accounting for insertion in the context of gp41. To account for the slow timescale of lipid mixing while enabling conformational changes, we implement a protocol to go back and forth between atomistic and coarse-grained simulations. Our study provides a molecular understanding of the interactions between the HIV-1 fusion peptide and the T-cell membrane, highlighting the importance of conformational flexibility of fusion peptides and local lipid reorganization in stabilizing the anchoring of gp41 into the targeted host membrane during the early events of HIV-1 cell entry. Importantly, we identify a motif within the fusion peptide critical for fusion that can be further manipulated in future immunological studies.

Predicting protein-peptide interactions is crucial for understanding peptide binding processes and designing peptide drugs. However, traditional computational modeling approaches face challenges in accurately predicting peptide-protein binding structures due to the slow dynamics and high flexibility of the peptides. Here, we introduce a new workflow termed "PepBinding" for predicting peptide binding structures, which combines peptide docking, all-atom enhanced sampling simulations using the Peptide Gaussian accelerated Molecular Dynamics (Pep-GaMD) method, and structural clustering. PepBinding has been demonstrated on seven distinct model peptides. In peptide docking using HPEPDOCK, the peptide backbone root-mean-square deviations (RMSDs) of their bound conformations relative to X-ray structures ranged from 3.8 to 16.0 Å, corresponding to the medium to inaccurate quality models according to the Critical Assessment of PRediction of Interactions (CAPRI) criteria. The Pep-GaMD simulations performed for only 200 ns significantly improved the docking models, resulting in five medium and two acceptable quality models. Therefore, PepBinding is an efficient workflow for predicting peptide binding structures and is publicly available at https://github.com/MiaoLab20/PepBinding.

B-cell receptor complexes (BCR) are expressed on the surface of a B-cell and are the critical regulators of adaptive immune response. Even though the relevance of antibodies has been known for almost a hundred years, the antigen-dependent activation of antibody-producing B-cells has remained elusive. Several models have been proposed for BCR activation, including cross-linking, conformation-induced oligomerization, and dissociation activation models. Recently, the first cryo-EM structure of the human B-cell antigen receptor of the IgM isotype was published. Given the new asymmetric BCR complex, we have carried out extensive molecular dynamics simulations to probe the conformational changes upon antigen binding and the influence of the membrane. We identified two critical dynamical events that could be associated with antigen-dependent activation of BCR. First, antigen binding caused increased flexibility in regions distal to the antigen binding site. Second, this increased flexibility led to the rearrangement of helices in transmembrane helices, including the relative interaction of Igα/Igβ, which has been responsible for intracellular signaling. Further, these transmembrane rearrangements led to changes in localized lipid composition. Even though the simulations considered only a single BCR complex, our work indirectly supports the dissociation activation model.

Background: Respiratory infections have long been recognized as a primary cause of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Additionally, the emergence of antimicrobial resistance has led to an urgent and critical situation in developing countries, including Vietnam. This study aimed to investigate the distribution and antimicrobial resistance of bacteria in patients with AE-COPD using both conventional culture and multiplex real-time PCR. Additionally, associations between clinical characteristics and indicators of pneumonia in these patients were examined., Methods: This cross-sectional prospective study included 92 AE-COPD patients with pneumonia and 46 without pneumonia. Sputum specimens were cultured and examined for bacterial identification, and antimicrobial susceptibility was determined for each isolate. Multiplex real-time PCR was also performed to detect ten bacteria and seven viruses., Results: The detection rates of pathogens in AE-COPD patients with pneumonia were 92.39%, compared to 86.96% in those without pneumonia. A total of 26 pathogenic species were identified, showing no significant difference in distribution between the two groups. The predominant bacteria included Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, followed by Acinetobacter baumannii and Streptococcus mitis. There was a slight difference in antibiotic resistance between bacteria isolated from two groups. The frequency of H. influenzae was notably greater in AE-COPD patients who experienced respiratory failure (21.92%) than in those who did not (9.23%). S. pneumoniae was more common in patients with stage I (44.44%) or IV (36.36%) COPD than in patients with stage II (17.39%) or III (9.72%) disease. ROC curve analysis revealed that C-reactive protein (CRP) levels could distinguish patients with AE-COPD with and without pneumonia (AUC = 0.78)., Conclusion: Gram-negative bacteria still play a key role in the etiology of AE-COPD patients, regardless of the presence of pneumonia. This study provides updated evidence for the epidemiology of AE-COPD pathogens and the appropriate selection of antimicrobial agents in Vietnam., (© 2024. The Author(s).)

The chemical screening of an octocoral identifed as Junceella fragilis has led to the isolation of five chlorinated briarane-type diterpenoids, including three known metabolites, gemmacolide X (1), frajunolide I (2), and fragilide F (3), along with two new analogs, 12α-acetoxyfragilide F (4) and 12α-acetoxyjunceellin (5). Single-crystal X-ray diffraction analysis was carried out to determine the absolute configurations of 1 and 2, while the structures of new compounds 4 and 5 were ascertained with 2D NMR experiments. Briaranes 1 and 3-5 were active in enhancing alkaline phosphatase (ALP) activity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Bis(3-indolyl)methanes (BIMs) are known for their important bioactivities, which include anti-cancer, anti-inflammatory, antibacterial, and antioxidant properties. In this study, we are disclosing a metal catalyst-free synthesis of BIMs in high yields via the alkylation reaction of indoles and alcohols in the presence of lithium tert -butoxide base. Notably, oxygen in air played an important role as an oxidant for the facilitation of this transformation. Interestingly, unactivated aliphatic alcohols could be successfully used as alkylating reagents in the alkylation reactions of indole. Especially, several chemical intermediates detected by GC-MS gave important information about the mechanism insights. This method demonstrated cost and environmental advantages for the development of green processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Higher education strongly focuses on shifting from a more traditional teaching approach - "instructivist" to a more student-centered approach - known as "constructivist" to encourage learning imperative key skills in a future turbulent environment. This study examines the application of new learning environment creation, integrated from applying the Design Science approach and Constructivism learning environment, on two critical elements of student evaluation, namely, students' learning motivation and their learning strategy in higher institutions. Quantitative research was adopted for the study. To do so, a new teaching and learning approach was developed and implemented specifically for one cohort. Instead of regularly joining a regular classroom, students can actively attend workshops to gain the skills, knowledge, and action they need to complete the course successfully. Following three months of implementation, 193 questionnaires were collected from all students who took a Project Management course. The data show that a constructivist learning environment encourages intrinsic and extrinsic motivation. Additionally, the student's learning strategy significantly improved in the new learning environment. These findings demonstrate that further attention should be given to constructivist orientation and implementation in the higher education curriculum., 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.)

G-protein-coupled receptors (GPCRs) make up the largest superfamily of human membrane proteins and represent primary targets of ∼1/3 of currently marketed drugs. Allosteric modulators have emerged as more selective drug candidates compared with orthosteric agonists and antagonists. However, many X-ray and cryo-EM structures of GPCRs resolved so far exhibit negligible differences upon the binding of positive and negative allosteric modulators (PAMs and NAMs). The mechanism of dynamic allosteric modulation in GPCRs remains unclear. In this work, we have systematically mapped dynamic changes in free energy landscapes of GPCRs upon binding of allosteric modulators using the Gaussian accelerated molecular dynamics (GaMD), deep learning (DL), and free energy prOfiling Workflow (GLOW). GaMD simulations were performed for a total of 66 μs on 44 GPCR systems in the presence and absence of the modulator. DL and free energy calculations revealed significantly reduced dynamic fluctuations and conformational space of GPCRs upon modulator binding. While the modulator-free GPCRs often sampled multiple low-energy conformational states, the NAMs and PAMs confined the inactive and active agonist-G-protein-bound GPCRs, respectively, to mostly only one specific conformation for signaling. Such cooperative effects were significantly reduced for binding of the selective modulators to "non-cognate" receptor subtypes. Therefore, GPCR allostery exhibits a dynamic "conformational selection" mechanism. In the absence of available modulator-bound structures as for most current GPCRs, it is critical to use a structural ensemble of representative GPCR conformations rather than a single structure for compound docking ("ensemble docking"), which will potentially improve structure-based design of novel allosteric drugs of GPCRs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family of receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib suppressed SARS-CoV-2 entry and later stages of the viral life cycle and showed synergistic effect with the direct-acting antiviral nirmatrelvir. We discovered that ErbB1, ErbB2, and ErbB4 bind SARS-CoV-2 S1 protein and regulate viral and ACE2 internalization, and they are required for VEEV infection. In human lung organoids, lapatinib protected from SARS-CoV-2-induced activation of ErbB-regulated pathways implicated in non-infectious lung injury, proinflammatory cytokine production, and epithelial barrier injury. Lapatinib suppressed VEEV replication, cytokine production, and disruption of blood-brain barrier integrity in microfluidics-based human neurovascular units, and reduced mortality in a lethal infection murine model. We validated lapatinib-mediated inhibition of ErbB activity as an important mechanism of antiviral action. These findings reveal regulation of viral replication, inflammation, and tissue injury via ErbBs and establish a proof of principle for a repurposed, ErbB-targeted approach to combat emerging viruses.

α 1 -adrenergic receptors (α 1 -ARs) play critical roles in the cardiovascular and nervous systems where they regulate blood pressure, cognition, and metabolism. However, the lack of specific agonists for all α 1 subtypes has limited our understanding of the physiological roles of different α 1 -AR subtypes, and led to the stagnancy in agonist-based drug development for these receptors. Here we report cryo-EM structures of α 1A -AR in complex with heterotrimeric G-proteins and either the endogenous common agonist epinephrine or the α 1A -AR-specific synthetic agonist A61603. These structures provide molecular insights into the mechanisms underlying the discrimination between α 1A -AR and α 1B -AR by A61603. Guided by the structures and corresponding molecular dynamics simulations, we engineer α 1A -AR mutants that are not responsive to A61603, and α 1B -AR mutants that can be potently activated by A61603. Together, these findings advance our understanding of the agonist specificity for α 1 -ARs at the molecular level, opening the possibility of rational design of subtype-specific agonists., (© 2023. Springer Nature Limited.)

Background: The progression into the Digital Age has brought an array of novel skill requirements. Unlike traditional literacy, there are currently few measures that can reliably measure eHealth literacy. The Transactional Model of eHealth Literacy and subsequent Transactional eHealth Literacy Instrument may provide a feasible option for measuring eHealth literacy., Objective: This instrument has yet to be validated, which is the aim of this study. In particular, this article was conducted to validate the TeHLI to see which components of the tool (how many and which components included) would be the best fit statistically and whether the tool applies to groups of different characteristics., Methods: We conducted an online cross-sectional study among 236 Vietnamese young people. A exploratory factor analysis was used to identify the best fit model of the Transactional eHealth Literacy Instrument. A confirmatory factor analysis tested measurement invariance at four levels: configural, metric, scalar, and strict invariance. Only metric invariance was partially invariant, while the rest tested fully invariant. Even with partial metric invariance, there is reason to assume that functional, communicative, critical, and translational eHealth literacy (the four levels according to the transactional model) are consistently measured when deploying the Transactional eHealth Literacy Instrument across groups., Results: The study findings substantiate that the most optimal composition of the TeHLI consists of four factors: functional, communicative, critical, and translational eHealth literacy, with RMSEA = 0.116; CFI = 0.907, and the highest internal consistency (Cronbach's α = 0.91, 0.92, 0.88, and 0.92 for each factor respectively). After using measurement invariance, that gender, education, marital status, age, location, and household economy do not influence the way participants to respond to the TeHLI to the point that would introduce measurement bias. In other word, using TeHLI across population groups should not produce error margins that substantially differ from each other., Conclusions: This study suggests the instrument can be used for comparisons across groups and has the potential to generate high-quality data usable for informing change agents as to whether a particular population is proficient enough to adopt novel eHealth innovations., 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 Nguyen, Do, Do, Vu, van Kessel, Wong, Boyer, Fond, Auquier, Nguyen, Latkin, Ho and Ho.)

The immunogenicity of a heterologous vaccination regimen consisting of ChAdOx1 nCoV-19 (a chimpanzee adenovirus-vectored vaccine) followed by mRNA-1273 (a lipid-nanoparticle-encapsulated mRNA-based vaccine) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), specifically the omicron variant (B.1.1.529), is poorly studied. The aim of this study was to evaluate the neutralizing antibody activity and immunogenicity of heterologous ChAdOx1 nCoV-19 and mRNA-1273 prime-boost vaccination against wild-type (BetaCoV/Korea/KCDC03/2020), alpha, beta, gamma, delta, and omicron variants of SARS-CoV-2 in Korea. A 50% neutralizing dilution (ND50) titer was determined in serum samples using the plaque reduction neutralization test. Antibody titer decreased significantly at 3 months compared with that at 2 weeks after the 2nd dose. On comparing the ND50 titers for the above-mentioned variants of concerns, it was observed that the ND50 titer for the omicron variant was the lowest. This study provides insights into cross-vaccination effects and can be useful for further vaccination strategies in Korea., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

During the process of adapting to metal contamination, plants produce secondary metabolites that have the potential to modulate multidrug-resistant (MDR) phenotypes; this is achieved by inhibiting the activity of efflux pumps to reduce the minimum inhibitory concentrations (MICs) of antimicrobial substrates. Our study evaluated the effect of secondary metabolites of belowground parts of Pteris vittata L. and Fallopia japonica, two metal-tolerant plants from northern Vietnam, on six antibiotic-resistant Stenotrophomonas maltophilia strains possessing efflux pump resistance mechanisms that were isolated from soil and clinical samples. The chemical composition of aqueous and dichloromethane (DCM) fractions extracted from P. vittata and F. japonica was determined using UHPLC-DAD-ESI/QTOF analysis. The antibacterial and efflux pump inhibitory activities of the four fractions were evaluated for the six strains (K279a, 0366, BurA1, BurE1, PierC1, and 502) using a microdilution assay at fraction concentrations of 62.5, 125, and 250 μg/mL. The DCM fraction of F. japonica exhibited remarkable antibacterial activity against strain 0366, with a MIC of 31.25 μg/mL. Furthermore, this fraction also significantly decreased gentamicin MIC: four-fold and eight-fold reductions for BurA1 and BurE1 strains, respectively (when tested at 250 μg/mL), and two-fold and eight-fold reductions for K279a and BurE1 strains, respectively (when tested at 125 μg/mL). Pure emodin, the main component identified in the DCM fraction of F. japonica , and sennidine A&B only reduced by half the MIC of gentamicin (when tested at 30 μg/mL). Our results suggest that the DCM fraction components of F. japonica underground parts may be potential candidates for new bacterial efflux pump inhibitors (EPIs).

Presenilin-1 (PS1) is the catalytic subunit of γ-secretase which cleaves within the transmembrane domain of over 150 peptide substrates. Dominant missense mutations in PS1 cause early-onset familial Alzheimer's disease (FAD); however, the exact pathogenic mechanism remains unknown. Here we combined Gaussian accelerated molecular dynamics (GaMD) simulations and biochemical experiments to determine the effects of six representative PS1 FAD mutations (P117L, I143T, L166P, G384A, L435F, and L286V) on the enzyme-substrate interactions between γ-secretase and amyloid precursor protein (APP). Biochemical experiments showed that all six PS1 FAD mutations rendered γ-secretase less active for the endoproteolytic (ε) cleavage of APP. Distinct low-energy conformational states were identified from the free energy profiles of wildtype and PS1 FAD-mutant γ-secretase. The P117L and L286V FAD mutants could still sample the "Active" state for substrate cleavage, but with noticeably reduced conformational space compared with the wildtype. The other mutants hardly visited the "Active" state. The PS1 FAD mutants were found to reduce γ-secretase proteolytic activity by hindering APP residue L49 from proper orientation in the active site and/or disrupting the distance between the catalytic aspartates. Therefore, our findings provide mechanistic insights into how PS1 FAD mutations affect structural dynamics and enzyme-substrate interactions of γ-secretase and APP., (© 2023. The Author(s).)

Purpose: Mental wellbeing and life satisfaction play an important role in the development of adolescents, yet factors potentially influencing these states have not been sufficiently studied, especially in Vietnam. This study aims to fill the research gaps by exploring the associations of the parent-child relationship, self-esteem, and resilience on the mental wellbeing and satisfaction with life of adolescents., Methods: A cross-sectional study was conducted from June to July 2020 on 1,023 adolescents from 10 to 18 years old living in Vietnam. To assess the satisfaction with life as well as the mental wellbeing of participants, this study used the Satisfaction with life and The World Health Organization-Five Wellbeing Index scale., Results: More than 70% of participants reported having conflicts with their parents (74.6% of those conflicted with their father ad 73.9% of those conflicted with their mother), while 26.3% stated dissatisfaction with life. The mean score of mental wellbeing was 61.5 (SD = 23.0). Higher academic performance, self-esteem, resilience, encounter loneliness and isolation within own family, and having support and sharing from family members had a positive effect on life satisfaction and mental wellbeing. Female participants had higher satisfaction with life score (Coef = 0.77; 95%CI = 0.10; 1.44) but they had a lower mental wellbeing score (Coef = -6.00; 95%CI = -8.57; -3.44) than male participants. High school students had lower both satisfaction with life and mental wellbeing scores than secondary students., Conclusion: The results highlight the importance of being aware of the influence that expectations (of higher grades) and bias (toward male children) imposed by parents, teachers, and society on the mental wellbeing of youths, especially in Asian cultures. Strengthening the family bond and encouraging young people to share their feeling is also crucial to enhancing the mental health condition of adolescents., 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 Trong Dam, Do, Thi Vu, Vu, Do, Thi Nguyen, Nguyen, Thi Vu, Thi Nguyen, Auquier, Boyer, Fond, Latkin, Ho and Ho.)

Introduction: This study aimed to determine latent profiles from the Problematic Internet Use Questionnaire Short Form-6 (PIUQ-SF-6) score of Vietnamese youths and adolescents, which supports the diagnosis of problematic internet use among a large sample size. Moreover, it also explored factors that affect each latent profile of the PIUQ-SF-6 score among participants., Methods: A sample of 1477 Vietnamese people, aged 14 to 24, across five provinces participated in the study. Multinomial logistic regression determined factors related to the levels of the Problematic Internet Use Questionnaire Short Form-6 (PIUQ-SF-6) after using latent profile analysis., Results: Participants were divided into three profiles, including those at low, moderate, and high risk of internet addiction. The high-risk latent profile was obtained for 23.1% of adolescents, and the remaining percentages were, respectively, 40.2% and 36.7% of adolescents belonging to the moderate and low-risk groups. Moreover, factors including age, living alone, high Kessler psychological distress scale, excessive time on the internet, living in central cities, and high neighborhood disorder scores were found to be related to moderate- and high-risk internet addiction profiles., Conclusions: Factors analyzed according to individual and social characteristics further explore the reasons underlying increasing internet addiction among Vietnamese youths and inform early interventions.

Background: Delayed childbearing has become a concern among policymakers across the world. In Vietnam, population policies have been adjusted to cope with this issue. In 2020, Decision 588/QD-TTg was ratified to encourage people to marry and give birth before the age of 30. This study reviewed recent changes in Vietnam's population policies and assessed the intention of giving birth before 30 in young Vietnamese to provide insights into the potential effectiveness of the policy changes among young people. Methods: This study combined two approaches: a desk review and a survey of a group of youths. An online cross-sectional study was conducted on 116 respondents aged 16 to 30 in Vietnam from June to July 2020. The intention of childbearing before 30 and the importance and responsiveness of different social-environmental factors were asked using a structured questionnaire. We used multivariate logistic regression to identify associated factors of such intention. Results: The incentives set out by the Vietnamese government shared similarities with those of other countries. The plan of childbearing before the age of 30 among young adults in Vietnam was demonstrated to correlate with age, socioeconomic and biological characteristics, resources of the local health systems, as well as a clean and safe living environment. Conclusion: This study highlighted the recent crucial shift in Vietnam's population policy. However, the quantitative analysis suggested that measures relating to environmental factors should be incorporated under this policy, implying that further interventions need to be taken into account to cope with delayed childbearing.

Background: Concerning rates of psychological disorders are increasingly recognized in young adults during the COVID-19 pandemic. This study aimed to examine the associations of different structural and functional social supports on depression, anxiety, and stress among young adults in Vietnam., Methods: An online cross-sectional study was performed on 236 respondents aged 16 to 30 years in Vietnam from June to July 2020. The Depression, Anxiety and Stress Scale-21 Items (DASS-21); the Multidimensional Scale of Perceived Social Support (MSPSS), and the LUBBEN Social Network Scale (LSNS-6) was used to measure psychological health, functional and structural social support characteristics. Multi-level mixed-effect logistic regression was used to identify associations between social support and anxiety, depression, and stress., Results: The rate of at least mild depression, anxiety, and stress were 30.1%, 34.8%, and 35.6%, respectively. Structural supports measured by LSNS-6 were not associated with the likelihood of having depression, anxiety, and stress (p>0.05). Respondents having friends with whom they could share joys and sorrows were less likely to have anxiety (aOR = 0.61, 95%CI = 0.41-0.90) and stress (aOR = 0.66, 95%CI = 0.45-0.96). Having family support in decision-making was also negatively associated with depression, anxiety, and stress. Meanwhile, those having family and friends who tried to help them were more likely to suffer stress (aOR = 1.94, 95%CI = 1.16-3.24) and depression (aOR = 2.09; 95%CI = 1.11-3.92), respectively., Conclusion: This study highlighted a high rate of psychological problems among young adults during the COVID-19 pandemic in Vietnam. Emotional support from friends and advice support from family were important components that should be considered in further interventions to mitigate the psychological problems in young adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Doan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Although the pathogenesis of depressive disorders is not fully elucidated, untreated adolescent depression can lead to serious sequelae such as impaired academic performance and social functioning, substance use disorders, poor self-esteem, and increased risk for suicidal ideation and attempts. Literature on adolescent mental health in Vietnam is limited, despite increased international awareness of this critical issue. This study aimed to investigate the prevalence and associations of depressive symptoms in Vietnamese adolescents., Methods: A cross-sectional, self-administered survey was conducted in five provinces of Vietnam among adolescents aged 14 to 24 years. In addition to collecting participants' demographics, a structured questionnaire was developed to examine depressive symptoms, suicidal ideation, loneliness, and cyberbullying victimization. Depressive symptoms and loneliness were assessed via the PHQ-9 and UCLA Loneliness Scale, respectively. Two-tailed Chi-squared, Mann-Whitney, and Kruskal-Wallis tests were performed to examine associations between variables. Multivariate Logistic regression models were conducted to examine the associations between prior-defined variables and positive depressive symptoms., Results: Among 1,600 respondents, 31.8% of participants reported having mild-moderate or severe depressive symptoms. Participants within the moderate-severe depressive symptom group had significantly lower community cohesion scores than those of participants in normal and mild depressive symptom groups ( p < 0.05). Youths living alone were more likely to have moderate-severe depressive symptoms (OR 2.16; 95% CI: 1.09-4.25). Cyberbullying had significant associations with depressive severity (OR 1.93; 95% CI 1.38-2.70)., Conclusion: The findings of this study characterize various risk and protective factors for depression in Vietnamese youths and adolescents. The results highlight the importance of raising awareness and increasing access to educational resources for depression and other mental health illnesses. With the rising prevalence of depression, parents, teachers, and community leaders play a vital role in addressing mental health problems in adolescents., 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 © 2022 Phan, Chau, Do, Vu, Vu, Nguyen, Nguyen, Do, Nguyen, La, Dam, Nguyen, Nguyen, Do, Vu, Vu Le, Vu, Le, Latkin, Ho and Ho.)

Gaussian accelerated molecular dynamics (GaMD) is a computational technique that provides both unconstrained enhanced sampling and free energy calculations of biomolecules. Here, we present the implementation of GaMD in the OpenMM simulation package and validate it on model systems of alanine dipeptide and RNA folding. For alanine dipeptide, 30 ns GaMD production simulations reproduced free energy profiles of 1000 ns conventional molecular dynamics (cMD) simulations. In addition, GaMD simulations captured the folding pathways of three hyperstable RNA tetraloops (UUCG, GCAA, and CUUG) and binding of the rbt203 ligand to the HIV-1 Tar RNA, both of which involved critical electrostatic interactions such as hydrogen bonding and base stacking. Together with previous implementations, GaMD in OpenMM will allow for wider applications in simulations of proteins, RNA, and other biomolecules.

G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of β 1 -adrenergic receptor (β 1 -AR) in complex with Gs (Gα s Gβ 1 Gγ 2 ) and a partial agonist or a very weak partial agonist, and compare them to the β 1 -AR-Gs structure in complex with a full agonist. Analyses reveal similar overall complex architecture, with local conformational differences. Cellular functional studies with mutations of β 1 -AR residues show effects on the cellular signaling from β 1 -AR to the cAMP response initiated by the three different ligands, with residue-specific functional differences. Biochemical investigations uncover that the intermediate state complex comprising β 1 -AR and nucleotide-free Gs is more stable when binding a full agonist than a partial agonist. Molecular dynamics simulations support the local conformational flexibilities and different stabilities among the three complexes. These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins., (© 2022. The Author(s).)

G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins. Four subtypes of adenosine receptors (ARs), the A 1 AR, A 2A AR, A 2B AR and A 3 AR, each with a unique pharmacological profile and distribution within the tissues in the human body, mediate many physiological functions and serve as critical drug targets for treating numerous human diseases including cancer, neuropathic pain, cardiac ischemia, stroke and diabetes. The A 1 AR and A 3 AR preferentially couple to the G i/o proteins, while the A 2A AR and A 2B AR prefer coupling to the G s proteins. Adenosine receptors were the first subclass of GPCRs that had experimental structures determined in complex with distinct G proteins. Here, we will review recent studies in molecular simulations and computer-aided drug discovery of the adenosine receptors and also highlight their future research opportunities.

Objective: The goal of the study was to explore the relationship between parent-children relationships related to using the internet among kids and potentially associated factors., Materials and Methods: A sample of 1.216 Vietnamese students between the ages of 12 and 18 agreed to participate in the cross-sectional online survey. Data collected included socioeconomic characteristics and internet use status of participants, their perceived changes in relationship and communication between parents and children since using the internet, and parental control toward the child's internet use. An Ordered Logistic Regression was carried out to determine factors associated with parent-children relationship since using the internet., Results: The characteristics of the relationship between children and their parents since using the Internet were divided into three levels: deterioration (7.0%), stability (78.2%), and improvement (14.8%). The topics that children most often communicate with their parents include learning, housework, and future directions. Two-way interactive activities, such as supporting parents to use the Internet, have a positive impact on the parent-child relationship. Stubborn parental control, such as establishing rules about contact or allowing Internet access and setting up global positioning system (GPS) to track negatively affecting parent-child relationships., Conclusion: Findings indicated that changes in the quality of the parent-child relationship were self-assessed by participants regard to kids' internet use, especially in the COVID-19 epidemic context. Educational campaigns and programs to raise awareness of parents as to the dangers and negative influences that their children may encounter online, psychology of children's behaviors and effects of different responding strategies are recommended., 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 © 2022 Nguyen, Nguyen, Do, Vu, Vu, Do, Nguyen, Doan, Vu, Do, Nguyen, Latkin, Ho and Ho.)

Biomolecular recognition including binding of small molecules, peptides and proteins to their target receptors plays a key role in cellular function and has been targeted for therapeutic drug design. However, the high flexibility of biomolecules and slow binding and dissociation processes have presented challenges for computational modeling. Here, we review the challenges and computational approaches developed to characterize biomolecular binding, including molecular docking, Molecular Dynamics (MD) simulations (especially enhanced sampling) and Machine Learning. Further improvements are still needed in order to accurately and efficiently characterize binding structures, mechanisms, thermodynamics and kinetics of biomolecules in the future.

Background: Seroprevalence studies of coronavirus disease 2019 (COVID-19) cases, including asymptomatic and past infections, are important to estimate the scale of the disease outbreak and to establish quarantine measures. We evaluated the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays available in Korea for use in seroprevalence studies., Methods: The sensitivity, specificity, cross-reactivity, and interference of five SARS-CoV-2 antibody assays were evaluated using the following: 398 serum samples from confirmed COVID-19 patients, 510 negative control samples from before 2018 (pre-pandemic), 163 serum samples from patients with SARS, Middle East respiratory syndrome (MERS), and other viral infections, and five samples for the interference study., Results: The sensitivities of the five assays ranged from 92.2% to 98%, and their specificities, including cross-reactivity and interference, ranged from 97.5% to 100%. The agreement rates were excellent (kappa >0.9). Adjustment of the cutoff values could be considered through ROC curve analysis. The positive predictive values of the individual assays varied from 3.5% to 100% at a 0.1% prevalence but were as high as ≥95% when two assays were combined., Conclusions: The prevalence of COVID-19 in Korea is considered to be exceptionally low at present; thus, we recommend using a combination of two or more SARS-CoV-2 antibody assays rather than a single assay. These results could help select SARS-CoV-2 antibody assays for COVID-19 seroprevalence studies in Korea.

Objectives: The Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide cross-sectional surveillance system that assesses the health and nutritional status of the Korean population. To evaluate the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the community, we investigated the prevalence of anti-SARS-CoV-2 antibodies in the sera of KNHANES participants., Methods: Subjects were recruited between April 24 and December 12, 2020. In total, 5,284 subjects aged 10-90 years from 17 regions participated. SARS-CoV-2 antibodies were screened using the Elecsys Anti-SARS-CoV-2 assay. Positive samples were verified using 4 different SARS-CoV-2 antibody assays and the plaque reduction neutralizing test. The final seropositivity criteria were a positive screening test and at least 1 positive result from the 5 additional tests., Results: Almost half (49.2%; 2,600/5,284) of participants were from metropolitan areas, 48.9% were middle-aged (40-69 years), and 20.5% were in their 20s or younger. The seropositivity rate was 0.09% (5/5,284). Three of the 5 antibody-positive subjects had a history of infection, of whom 2 were infected abroad and 1 was infected in a local cluster outbreak., Conclusions: The low SARS-CoV-2 antibody seroprevalence in Korea indicates that there have been few coronavirus disease 2019 (COVID-19) cases due to successful COVID-19 management measures (e.g., diagnostic tests for overseas arrivals, national social distancing, and strict quarantine measures). Moreover, asymptomatic infections were uncommon due to active polymerase chain reaction testing. However, hidden infections may exist in the community, requiring the continuation of quarantine and vaccination measures.

Objectives: After the third wave of coronavirus disease 2019 (COVID-19), by mid-February 2021, approximately 0.16% of the Korean population was confirmed positive, which appeared to be among the lowest rates worldwide at that time. However, asymptomatic transmission is challenging for COVID-19 surveillance. Therefore, a community-based serosurvey of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted to understand the effectiveness of Korea's strong containment strategy., Methods: We collected 5,002 residual sera samples from January 30 to March 3, 2021, from 265 medical facilities in Seoul, 346 in Gyeonggi Province, and 57 in Incheon. Sixty samples from tertiary institutions were excluded. We defined the sub-regions according to the addresses of the medical facilities where the specimens were collected. Elecsys Anti-SARS-CoV-2 was used for screening, and positivity was confirmed using the SARS-CoV-2 sVNT Kit. Prevalence was estimated using sampling weights and the Wilson score interval for a binomial proportion with a 95% confidence interval., Results: Among the 4,942 specimens, 32 and 25 tested positive for COVID-19 in the screening and confirmatory tests, respectively. The overall crude prevalence of SARS-CoV-2 antibodies was 0.51%. The population-adjusted overall prevalence was 0.55% in women and 0.38% in men. The region-specific estimation was 0.67% and 0.30% in Gyeonggi Province and Seoul, respectively. No positive cases were detected in Incheon., Conclusions: The proportion of undetected cases in Korea remained low as of early 2021. Therefore, an infection control strategy with exhaustive tracing and widespread pre-emptive testing appears to be effective in containing community spread of COVID-19.

Purpose: The mainstay of treatment for basal cell carcinoma (BCC) is surgical excision, which can result in significant associated morbidity, particularly for patients with recurrent tumors. We previously conducted a drug repositioning screen using molecular data from human BCCs and identified histone deacetylase (HDAC) inhibitors as a potential treatment for BCC. Here we conduct the first proof-of-principle study of a topical pan-HDAC inhibitor, remetinostat, in human BCC., Patients and Methods: We conducted a phase II, open-label, single-arm, single-institution trial of a topical HDAC inhibitor. Participants with at least one BCC were recruited. All participants applied 1% remetinostat gel three times daily for 6 weeks, with measurements of tumor diameter conducted at baseline and week 8. Surgical excision of the remaining tumor was conducted at the end of the study and microscopic evaluation was performed., Results: Thirty-three per-protocol tumors from 25 participants were included in the analysis. The overall response rate, defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8, was 69.7% [90% confidence interval (CI), 54%-82.5%]. On pathologic examination, 54.8% of tumors demonstrated complete resolution. Pharmacodynamic analysis demonstrated similar levels of acetylated histone H3 in skin tissue before and after treatment, however, phosphorylation was increased. No systemic adverse events were reported., Conclusions: The HDAC inhibitor remetinostat is a well-tolerated and effective topical treatment for reducing BCC disease burden in a clinically significant manner. This provides in-human validation of HDAC inhibitors as a therapy for BCC., (©2021 American Association for Cancer Research.)

This study was performed to evaluate the measurement properties of Youth Quality of Life-Short Form (YQOL-SF) in assessing the quality of life (QOL) among general youths in Vietnam. An online cross-sectional study was conducted to validate the YQOL-SF. Factor analysis (including exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) was utilized to determine the factorial structure of this tool. The psychometric properties (reliability and validity) of the new factorial model were assessed. The factor analysis revealed the two-factor model of YQOL-SF including factor 1 "Belief in self and family", and factor 2 "Environment and relationships". Cronbach's alpha value showed excellent internal consistency in both factors (0.911 and 0.910, respectively). Results also indicated good convergent, divergent, concurrent, and know-group validity of the two-factor model. Our study provided a promising model with different domains that were proved to be essential for the assessment of quality of life among Vietnamese youth aged 16-24. Our two-factor model affirmed that a balance between detail and length of the assessment is important to consider when selecting YQOL-SF for youths' QOL assessment. It helped reduce the risk of redundancy and encourages high survey completion rates among participants., Competing Interests: The authors have declared that no competing interests exist.

Caffeine (CFF) is a common antagonist to the four subtypes of adenosine G-protein-coupled receptors (GPCRs), which are critical drug targets for treating heart failure, cancer, and neurological diseases. However, the pathways and mechanism of CFF binding to the target receptors remain unclear. In this study, we have performed all-atom-enhanced sampling simulations using a robust Gaussian-accelerated molecular dynamics (GaMD) method to elucidate the binding mechanism of CFF to human adenosine A 2A receptor (A 2A AR). Multiple 500-1,000 ns GaMD simulations captured both binding and dissociation of CFF in the A 2A AR. The GaMD-predicted binding poses of CFF were highly consistent with the x-ray crystal conformations with a characteristic hydrogen bond formed between CFF and residue N6.55 in the receptor. In addition, a low-energy intermediate binding conformation was revealed for CFF at the receptor extracellular mouth between ECL2 and TM1. While the ligand-binding pathways of the A 2A AR were found similar to those of other class A GPCRs identified from previous studies, the ECL2 with high sequence divergence serves as an attractive target site for designing allosteric modulators as selective drugs of the A 2A AR., 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 Do, Akhter and Miao.)

Many of today's online services are designed specifically to encourage impulse buying. Moreover, many studies have shown that with the assistance of Mobile Augmented Reality, retailers have the potential to significantly improve their sales. However, the effects of Mobile AR on consumer impulse buying behavior have yet to be examined, particularly in the tourism field. Consequently, the present study integrates the Technology Acceptance Model (TAM), Stimulus-Organism-Response (SOR) framework, and flow theory to examine the effects of Mobile AR apps on tourist impulse buyingbehavior. The research model is implemented using an online questionnaire, with the results analyzed by Partial-Least-Squares Structural Equation Modeling (PLS-SEM) approach. The results obtained from 479 valid samples show that the characteristics of Mobile AR apps play an important role in governing tourist behavior in making unplanned purchases. In particular, as the utility, ease-of-use, and interactivity of the apps increase, the perceived enjoyment and satisfaction of the user also increase and give rise to a stronger impulse buying behavior. The results also reveal a mediating effect of the flow experience on the relationship between the perceived ease of use of the Mobile AR app and the user satisfaction in using the app. Overall, the findings presented in this study provide a useful source of reference for Mobile AR app developers, retailers, and tourism marketers in better understanding users' preferences for Mobile AR apps and strengthening their impulse buying behavior in the tourism context as a result., (© 2020 The Author(s).)

Background : Depressive symptoms and suicidal ideation substantially reduce industrial workers' productivity and performance. This study was performed to examine the prevalence of depressive symptoms and suicidal ideation and identify associated factors among industrial workers in different provinces of Vietnam. Materials and Methods : We performed a cross-sectional study in industrial zones of four provinces of Vietnam. The Patient Health Questionnaire (PHQ-9) was employed to screen depressive symptoms and suicidal ideation. Multivariate logistic regression was performed to determine factors related to depressive symptoms and suicidal ideation. Results : Of 1200 industrial workers, 30.5% and 33.6% industrial workers had positive depressive symptoms and suicidal ideation in the last two weeks, respectively. There were 38.3% ever using mental health services in the last 12 months. High school education (OR = 0.64, 95% CI = 0.44-0.95); living in dormitory (OR = 3.07, 95% CI = 1.51-6.24), living with siblings (OR = 2.98; 95% CI = 1.32-6.75), having two children or more (OR = 1.45, 95% CI = 1.03-2.03), high years of experience (OR = 0.94; 95% CI = 0.89-0.98), suffering from burnout, alcohol use disorder (OR = 2.38; 95% CI = 1.72-3.28), and smoking status (OR = 0.38, 95% CI = 0.23-0.61) were associated with positive depressive symptoms. Living with children, working in mechanical/metallurgy/electronics factories, completely exhausted and often thinking of quitting, and alcohol use disorder were positively related to suicidal ideation. Conclusions : This study found a high prevalence of depressive symptoms and suicidal ideation among industrial workers in Vietnam. Regular screening and detecting high-risk groups, along with interventions to reduce health risk behaviors, burnout and on-site medical service quality improvement, are recommended to alleviate the burden of depression in industrial workers.

Background: Sustainability of methadone maintenance treatment (MMT) program involves regularly assessing its impact on health and social outcomes of drug users in different settings, particularly in disadvantaged areas. In this study, we evaluated the change in quality of life (QoL), and identified associated factors amongst drug users over the course of 12-month MMT in Vietnamese mountainous provinces., Methods: We conducted a longitudinal study among patients from 6 MMT clinics in three mountainous provinces of Vietnam. At baseline, we screened 300 participants and after a 12-month treatment, 244 participants remained to involve in the study. World Health Organization Quality of Life short form instrument (WHOQOL-BREF) was used to measure the QoL of patients. The magnitude of the changes was extrapolated., Results: There were significant changes in all four dimensions of quality of life measured by WHOQoL-BREF between baseline and 12 months with the effect size ranged from 0.21 to 0.24. Increased age, being workers compared to unemployment and having health problems or comorbidities were positively related to reduced scores of QoL., Conclusions: To conclude, we observed a significant increase in the QoL level regarding physical, psychological, social relationships and environmental aspects among people who used drug after 12 months of MMT. Findings from this study emphasize the role of continuously receiving MMT treatment among people using drugs to enhance their QoL.

Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.

The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC). Although tumor tissue biopsy remains the gold standard for diagnosis of NSCLC, the analysis of circulating tumor DNA (ctDNA) in plasma, known as liquid biopsy, has recently emerged as an alternative and noninvasive approach for exploring tumor genetic constitution. In this study, we developed a protocol for liquid biopsy using ultra-deep massively parallel sequencing (MPS) with unique molecular identifier tagging and evaluated its performance for the identification and quantification of tumor-derived mutations from plasma of patients with advanced NSCLC. Paired plasma and tumor tissue samples were used to evaluate mutation profiles detected by ultra-deep MPS, which showed 87.5% concordance. Cross-platform comparison with droplet digital PCR demonstrated comparable detection performance (91.4% concordance, Cohen's kappa coefficient of 0.85 with 95% CI = 0.72-0.97) and great reliability in quantification of mutation allele frequency (Intraclass correlation coefficient of 0.96 with 95% CI = 0.90-0.98). Our results highlight the potential application of liquid biopsy using ultra-deep MPS as a routine assay in clinical practice for both detection and quantification of actionable mutation landscape in NSCLC patients., Competing Interests: This research is funded by The Vietnam National Foundation for Science and Technology Development (NAFOSTED, https://nafosted.gov.vn/) under grant number 108.01-2017.306 (to HNN) and Ho Chi Minh city Department of Science and Technology under grant number 257/2017/HD-SKHCN (to HNN) and Gene Solutions (GS-003). We confirm that the funder Gene Solutions provided support in the form of salaries for authors LS Tran, HAT Pham, VU Tran, TT Tran, BT Vo, HTT Dao, NH Nguyen, HN Do, M-D Phan and H Giang but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. We also confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Soybeans offer an abundant source of isoflavones, which confer useful bioactivities when existing in aglycone forms. The conversion of isoflavones into aglycones via fermentation of soybean products is often realized by β-glucosidase, an enzyme produced by fungi. In this study, a filamentous fungus, Clerodendron cyrtophyllum , was isolated from root of Clerodendron cyrtophyllum Turcz, which was able to produce the highest activity of β-glucosidase up to 33.72 U/mL at 144 h during fermentation on Potato Dextrose Broth (PDB). The obtained fungus was grown on isoflavones-rich soybean extract to produce genistein and daidzein, achieving the conversion rate of 98.7%. Genistein and daidzein were isolated and purified by column chromatography using hexane/acetone (29:1/1:1), reaching purities of over 90% of total isoflavones, as identified and determined by TLC, LC-MS/MS, and 1 H and 13 C NMR spectroscopy. These results imply that the isolated P. citrinum is a potential fungal strain for industrial-scale production of genistein and daidzein from isoflavones-containing soybean extracts. These products may serve as potential raw materials for manufacture of functional foods that are based on aglycones.

Child sexual abuse has become a significant public health concern in Vietnam in recent years, and the likelihood of being abused could be prevented by increasing the awareness of sexual abuse and self-protection skills among children. However, little is known about the perception and attitude of schoolchildren toward this issue in Vietnam. This study aimed to evaluate the knowledge and attitude of school-age children toward child sexual abuse and the risk factors affecting their knowledge and attitude. A cross-sectional study was conducted among 800 Vietnamese students from grades four to nine. Most of the respondents had insufficient knowledge of sexual abuse in children; teachers and strangers would not be perpetrators (57.9% and 74%); and schools and home were safe places (55.8% and 58.8%). Almost all participants disagreed with touching and non-touching actions, even from acquaintances (94.5% to 99.5%). Being female, older age, not living with family or relatives, and living in an urban setting were found to be positively associated with the right perception and attitude toward child sexual abuse. A sexuality education program should be officially applied at schools for children with the support of their parents to narrow the knowledge gap between different geographical locations and genders.

Methadone maintenance treatment (MMT) programs have been used worldwide to reduce the number of drug users and for HIV prevention; however, evidence of their effectiveness in mountainous areas is limited. This study aimed to identify changes in substance abuse and sexual practices among MMT patients after treatment in three Vietnamese mountainous provinces. A survey on risk behaviors was conducted among 300 drug users in six MMT clinics prior to and following one year of MMT. Cramér's effect size of changes was extrapolated to justify the magnitude of the intervention's effectiveness. A generalized estimation equation was used to find the factors associated with respondents' substance use and sexual risk behavior. While drug-related risk behaviors were significantly reduced, alcohol and sex-related behaviors remained risk factors for HIV in this group. Additionally, condom use was common among participants at both time points, but not among those having sex with sex workers. Socio-economic characteristics of ethnic, education, occupation, as well as drug use history influenced the possibility of engaging in drug use and/or sexual risk behavior following treatment. Further emphasis on managing these among MMT patients is required, potentially by providing integrated services including smoking and drinking counseling and condom use promotion in accordance with MMT.

Objective: We propose a novel approach to predict the Abdominal Aortic Aneurysm (AAA) growth in future time, using longitudinal computer tomography (CT) scans of AAAs that are captured at different times in a patient-specific way., Methods: We adopt a formulation that considers a surface of the AAA as a manifold embedded in a scalar field over the three dimensional (3D) space. For this formulation, we develop our Dynamical Gaussian Process Implicit Surface (DGPIS) model based on observed surfaces of 3D AAAs as visible variables while the scalar fields are hidden. In particular, we use Gaussian process regression to construct the field as an observation model from CT training image data. We then learn a dynamic model to represent the evolution of the field. Finally, we derive the predicted AAA surface from the predicted field along with uncertainty quantified in future time., Results: A dataset of 7 subjects (4-7 scans) was collected and used to evaluate the proposed method by comparing its prediction Hausdorff distance errors against those of simple extrapolation. In addition, we evaluate the prediction results with respect to a conventional shape analysis technique such as Principal Component Analysis (PCA). All comparative results show the superior prediction performance of the proposed approach., Conclusion: We introduce a novel approach to predict the AAA growth and its predicted uncertainty in future time, using longitudinal CT scans in a patient-specific fashion., Significance: The capability to predict the AAA shape and its confidence region by our approach establish the potential for guiding clinicians with informed decision in conducting medical treatment and monitoring of AAAs.

Background: Residents in border areas are vulnerable to HIV/AIDS due to high rates of risk behaviors such as unprotected sexual practices or illicit drug use. Improving knowledge and attitude toward HIV/AIDS prevention and treatment are vital to diminish the burden of the HIV epidemic in this setting. However, evidence about this issue in Vietnam has been limited. This study aims to explore the knowledge and attitude toward HIV/AIDS among people in Vietnam border zones., Methods: We conducted a cross-sectional study in three border communes in Thanh Hoa province with 600 HIV(-) residents. Data about socio-demographic characteristics, general HIV knowledge, knowledge about prevention of mother-to-child transmission, treatment and care, HIV testing services, and attitude toward HIV/AIDS were collected. Multivariate Tobit regression was used to determine related factors with the knowledge and attitude., Results: The highest percentage of people having correct statements was for "HIV could be transmitted from mother to child" (98.2%), while the lowest percentage was for item "Know health facilities where HIV-positive people could register for care and check-up" (28.2%). People had the highest score in "Knowledge about HIV transmission routes" and the lowest score in "Knowledge about HIV/AIDS prevention measures". Most of the people were not afraid of being exposed to HIV-positive individuals (66.0%), willing to buy goods from HIV-positive sellers (78.9%), and willing to take care of people living with HIV in their family (90.1%). Education, ethnic, marital status, occupations, and HIV/AIDS information sources were found to be associated with knowledge and attitude toward HIV/AIDS., Conclusions: The general knowledge and attitude on HIV/AIDS of residents were relatively good. Educational campaigns to improve knowledge and attitude toward PLWH, involving peer educators and local associations, are potential strategies for sustaining HIV intervention in this remote setting.

Although antiretroviral treatment (ART) access has been universal in recent years, few studies have examined if this policy contributes to the mental health of the patients. This study assessed depression and its relations with health-related quality of life (HRQOL), which is defined as the status of general well-being, physical, emotional, and psychological, among HIV patients. A cross-sectional study was conducted in 482 patients at five outpatient clinics. Patient Health Questionnaire-9 (PHQ-9) and EuroQol-5 dimensions-5 levels (EQ-5D-5L) were used to assess the severity of depression and HRQOL. About one-fifth of patients reported symptoms of depression. According to the result of a multivariate logistic regression model, patients who had a lower number of CD4 cells at the start of ART, who received ART in the clinic without HIV counseling and testing (HCT) services, who had a physical health problem, and who experienced discrimination were more likely to have depression. Depression was associated with significantly decreased HRQOL. Depression is prevalent and significantly negatively associated with HRQOL of HIV/AIDS patients. We recommend screening for depression and intervening in the lives of depressed individuals with respect to those who start ART late, and we also recommend community-based behavioral change campaigns to reduce HIV discrimination.

Methadone Maintenance Treatment (MMT) program has been considered a medium through which human immunodeficiency virus (HIV) risks assessment and prevention on drug use/HIV-infected population can be effectively conducted. Studies concerning the implementation of such idea on patients in remote, under-developed areas, however, have been limited. Having the clinics established in three mountainous provinces of Vietnam, this study aimed to evaluate the changes in knowledge of HIV, perceived risk, and HIV testing uptake of the patients. A longitudinal study was conducted at six MMT clinics in three provinces with a pre- and post-assessments among 300 patients. Outcomes of interest were compared between baseline and after 12 months. The magnitude of changes was extrapolated. The proportion of participants reporting that their HIV knowledge was not good fell by 4.4% (61.3% at the baseline vs. 56.8% at 12 months). The significant improvement seen was in the knowledge that needle sharing was a mode of transmission (82.7% vs. 89.6%). Nevertheless, the majority of participants reportedly considered mosquitoes/insect and eating with the HIV-infected patient were the route of transmission at both time points (84.7% vs. 89.1%, 92.2% vs. 93.3%, respectively). This study found a limited improvement in HIV knowledge and testing uptake among MMT patients following a 12-month period. It also highlighted some shortcomings in the knowledge, attitudes and practices (KAP) of these patients, in particular, incorrect identification of HIV transmission routes, among patients both at program initiation and follow-up. The findings lent support to the argument for enhancing education and counseling efforts at MMT clinics regarding HIV, as well as for improving access to preventive and health care services through the integration of MMT/HIV services.

Purpose: This study aimed to assess the antiretroviral therapy (ART) compliance among patients with HIV/AIDS and its associated factors in the context of universal ART initiation in Vietnam., Patients and Methods: A cross-sectional survey was conducted in five ART clinics located in three provinces, such as Hanoi, Thanh Hoa, and Lao Cai, from July to September 2017. Overall, adherence to ART in the last month was measured using a 100-point Visual Analog Scale (VAS). Besides, information about forgetting doses in the last 4 days and delaying taking pills in the last 7 days was also reported., Results: Among 482 patients, the suboptimal adherence rate was 54.5%. Noncurrent smoking (coefficient =4.19, 95% CI 0.42-7.97), higher baseline CD4 count (coefficient =4.35, 95% CI 0.58-8.13), and no traveling difficulties (coefficient =6.17, 95% CI 2.27-10.06) were predictors of higher VAS adherence score. Suboptimal adherence was associated with mountainous residence (OR =5.34, 95% CI 2.81-10.16). Female respondents were less likely to delay taking pills in the last 7 days (OR =0.19, 95% CI 0.07-0.52)., Conclusion: Our study embraced early ART initiation in Vietnam; however, this approach should be parallel with appropriate resource allocation and service delivery., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Due to their geographical characteristics, the mountainous areas of Vietnam are particularly vulnerable to illicit drug use. Drug users in remote areas are also more likely to engage in risky sexual behaviors. This study aimed to describe the prevalence and characteristics of substance use and sexual behaviors and explored their related factors among newly admitted drug users in three mountainous provinces of Vietnam. A cross-sectional study was conducted on 300 newly-admitted drug users registering for Methadone Maintenance Treatment (MMT) at 6 clinics in three provinces: Dien Bien, Lai Chau and Yen Bai from October 2014 to December 2015. Information about the socio-demographic characteristics, history of substance use, and sexual behaviors were collected. The multivariate logistic regression model was used to identify potential predictors of four outcomes, which included: drug injection, re-use of needles, using condoms during the last time of having sex, and having sexual intercourse with female sex workers. The proportion of injecting drug users was 68.3%; of those 9% never re-used needles. Of note, 69% of those who reported having sex with female sex workers in the last month did not use condoms. Regression models showed that those who injected drugs and had health problems in last 30 days had greater odds of having sex with female sex workers. Drug users in mountainous settings acknowledged the high prevalence of human immunodeficiency virus (HIV)-related risk behaviors and a demand for physical and psychological care. Scaling up MMT services is key to approaching this high-risk group; however, at the same time, comprehensive harm-reduction interventions, counseling, and health care services should also be made accessible and effective in this setting.

Child maltreatment remains a major health threat globally that requires the understanding of socioeconomic and cultural contexts to craft effective interventions. However, little is known about research agendas globally and the development of knowledge-producing networks in this field of study. This study aims to explore the bibliometric overview on child maltreatment publications to understand their growth from 1916 to 2018. Data from the Web of Science Core Collection were collected in May 2018. Only research articles and reviews written in the English language were included, with no restrictions by publication date. We analyzed publication years, number of papers, journals, authors, keywords and countries, and presented the countries collaboration and co-occurrence keywords analysis. From 1916 to 2018, 47,090 papers (53.0% in 2010⁻2018) were published in 9442 journals. Child Abuse & Neglect (2576 papers; 5.5%); Children and Youth Services Review (1130 papers; 2.4%) and Pediatrics (793 papers, 1.7%) published the most papers. The most common research areas were Psychology (16,049 papers, 34.1%), Family Studies (8225 papers, 17.5%), and Social Work (7367 papers, 15.6%). Among 192 countries with research publications, the most prolific countries were the United States (26,367 papers), England (4676 papers), Canada (3282 papers) and Australia (2664 papers). We identified 17 authors who had more than 60 scientific items. The most cited papers (with at least 600 citations) were published in 29 journals, headed by the Journal of the American Medical Association (JAMA) (7 papers) and the Lancet (5 papers). This overview of global research in child maltreatment indicated an increasing trend in this topic, with the world&rsquo;s leading centers located in the Western countries led by the United States. We called for interdisciplinary research approaches to evaluating and intervening on child maltreatment, with a focus on low-middle income countries (LMICs) settings and specific contexts.

Reference ranges of standard experimental parameters are useful for comparisons in toxicology. The aim of this study was to collect data from 13-week repeated toxicity studies in Crl:CD (SD) rats, a strain widely used for toxicity and efficacy research, for establishing domestic reference values. Data on body weight, food consumption; urinalysis, hematological, and blood biochemical parameters; and organ weights were collected from 11 toxicity studies in 220 Crl:CD (SD) rats (110 males and 110 females). The studies had been performed at a single testing facility over the last 5 years and involved animals sourced from a single breeder. The findings were collated as means, standard deviations, percentages, and ranges. Urine volume, uterus weight, eosinophil, and basophil counts, and triglyceride, total bilirubin, and gamma-glutamyl transpeptidase levels showed standard deviations of 30% or more. These historical control data would help to interpret the effects of test substances in routine toxicity and efficacy studies.