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Biology subjects

Nguyen, D. T.

Publications and source records attributed to Nguyen, D. T..

54 records · Page 3Linked to original sources

The Tryptophan Metabolizing Enzyme Indoleamine 2,3-Dioxygenase 1 Regulates Polycystic Kidney Disease Progression

Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic nephropathy, is characterized by phenotypic variability exceeding genic effects. Dysregulated metabolism and immune cell function are key disease modulators. The tryptophan metabolites, kynurenines, produced through IDO1, are known immunomodulators. Here, we study the role of tryptophan metabolism in PKD using an orthologous disease model (C57Bl/6J Pkd1RC/RC). We found elevated kynurenine and IDO1 levels in Pkd1RC/RC kidneys versus wildtype. Further, IDO1 levels were increased in ADPKD cell lines and patient cyst cells. Genetic Ido1 loss in Pkd1RC/RC animals resulted in reduced PKD severity as measured by %kidney weight/body weight and cystic index. Consistent with a immunomodulatory role of kynurenines, Pkd1RC/RC;Ido1-/- mice presented with significant changes in the cystic immune microenvironment (CME) versus controls. Of note, kidney macrophage numbers decreased and CD8+ T cell numbers increased, both known PKD modulators. Also, pharmacological IDO1 inhibition using a tryptophan analog in Pkd1RC/RC animals resulted in less severe PKD versus controls with similar changes in the CME as in the genetic model. Together, our data suggest that tryptophan metabolism is dysregulated in ADPKD and that its inhibition results in changes to the CME and slows disease progression, making IDO1 a novel therapeutic target for ADPKD.

molecular biology↗

Immune Checkpoint Activity Regulates Polycystic Kidney Disease Progression

Innate and adaptive immune cells modulate Autosomal Dominant Polycystic Kidney Disease (ADPKD) severity, a common kidney disease with inadequate treatment options. ADPKD shares parallels with cancer where immune checkpoint inhibitors have been shown to reactivate CD8+ T cells and slow tumor growth. We have shown that, in PKD, CD8+ T cell loss worsens disease. This study used orthologous early-onset and adult-onset ADPKD models (Pkd1 p.R3277C) to evaluate the role of immune checkpoints in PKD. Flow cytometry of kidney cells showed increased levels of PD-1 on CD8+ T cells and PD-L1 on macrophages and epithelial cells in Pkd1RC/RC mice versus wildtypes, paralleling disease severity. PD-L1 was also upregulated in ADPKD human cells and patient kidney tissue versus controls. Genetic PD-L1 loss or treatment with an anti-PD-1 antibody did not impact PKD severity in early-onset or adult-onset ADPKD models. However, treatment with anti-PD-1 plus anti-CTLA-4, blocking two immune checkpoints, improved PKD outcomes in adult-onset ADPKD mice; neither monotherapy altered PKD. Combination therapy resulted in increased kidney CD8+ T cell numbers/activation and decreased kidney regulatory T cell numbers. Together, our data suggests that immune checkpoint activation is an important feature of and potential novel therapeutic target in ADPKD.

immunology↗

LmTag: functional-enrichment and imputation-aware tag SNP selection for population-specific genotyping arrays

Despite the rapid development of sequencing technology, single-nucleotide polymorphism (SNP) array is still the most cost-effective genotyping solutions for large-scale genomic research and applications. Recent years have witnessed the rapid development of numerous genotyping platforms of different sizes and designs, but population-specific platforms are still lacking, especially for those in developing countries. We aim to develop methods to design SNP arrays for thse countries, so the arrays should be cost-effective (small size), yet can still generate key information needed to associate genotypes with traits. A key design principle for most current platforms is to improve genome-wide imputation so that more SNPs (imputed tag SNPs) not included in the array can be predicted. However, current tag SNP selection methods mostly focus on imputation accuracy and coverage, but not the functional content of the measured and imputed SNPs. It is those functional SNPs that are most likely associated to traits. Here, we propose LmTag, a novel method for tag SNP selection that not only improves imputation performance but also prioritizes highly functional SNP markers. We apply LmTag on a wide range of populations using both public and in-house whole genome sequencing databases. Our results showed that LmTag improved both functional marker prioritization and genome-wide imputation accuracy compared to existing methods. This novel approach could contribute to the next generation genotyping arrays that provide excellent imputation capability as well as facilitate array-based functional genetic studies. Such arrays are particularly suitable for under-represented populations in developing countries or non-model species, where little genomics data are available while investment in genome sequencing or high-density SNP arrays is limited.

bioinformatics↗

Astroglial CD38 regulates social memory and synapse formation through SPARCL1 in the medial prefrontal cortex

Social behavior is essential for the health, survival and reproduction of animals, yet the role of astrocytes in social behavior is largely unknown. CD38 is critical for social behaviors by regulating oxytocin release from hypothalamic neurons. On the other hand, CD38 is most abundantly expressed in astrocytes especially in the postnatal cortex, and is important for astroglial development. Here, we demonstrate that astroglial CD38 plays a pivotal role in the social behavior. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, specifically impaired social memory without any other behavioral abnormalities. Morphological analysis revealed reductions in spine numbers, mature spines and excitatory synapse numbers in the pyramidal neurons of the medial prefrontal cortex (mPFC) due to deletion of astroglial CD38 in the postnatal brain. Astrocyte-conditioned medium (ACM) of CD38 KO astrocytes reduced synaptogenesis of cortical neurons by reducing extracellular SPARCL1, a synaptogenic protein. Finally, the release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. Our data indicate that astroglial CD38 developmentally regulates social memory and neural circuit formation in the developing brain by promoting synaptogenesis through SPARCL1.

neuroscience↗

Natural and designed proteins inspired by extremotolerant organisms can form condensates and attenuate apoptosis in human cells

Many organisms can survive extreme conditions and successfully recover to normal life. This extremotolerant behavior has been attributed in part to repetitive, amphipathic, and intrinsically disordered proteins that are upregulated in the protected state. Here, we assemble a library of approximately 300 naturally-occurring and designed extremotolerance-associated proteins to assess their ability to protect human cells from chemically-induced apoptosis. We show that several proteins from tardigrades, nematodes, and the Chinese giant salamander are apoptosis protective. Notably, we identify a region of the human ApoE protein with similarity to extremotolerance-associated proteins that also protects against apoptosis. This region mirrors the phase separation behavior seen with such proteins, like the tardigrade protein CAHS2. Moreover, we identify a synthetic protein, DHR81, that shares this combination of elevated phase separation propensity and apoptosis protection. Finally, we demonstrate that driving protective proteins into the condensate state increases apoptosis protection, and highlight the ability for DHR81 condensates to sequester caspase-7. Taken together, this work draws a link between extremotolerance-associated proteins, condensate formation, and designing human cellular protection.

synthetic biology↗

Multiple generations of antibiotic exposure and isolation influence host fitness and the microbiome in a model zooplankton species

BackgroundChronic antibiotic exposure impacts host health through changes to the microbiome, increasing disease risk and reducing the functional repertoire of community members. The detrimental effects of antibiotic perturbation on microbiome structure and function after one host generation of exposure have been well-studied. However, much less is understood about the multigenerational effects of antibiotic exposure and how the microbiome may recover across host generations. ResultsIn this study, we examined microbiome composition and host fitness across five generations of exposure to a suite of three antibiotics in the model zooplankton host Daphnia magna. By utilizing a split-brood design where half of the offspring from antibiotic-exposed parents were allowed to recover and half were maintained in antibiotics, we aimed to examine recovery and resilience of the microbiome. Unexpectedly, we discovered that experimental isolation of single host individuals across generations also exerted a strong effect on microbiome composition, with composition becoming less diverse over generations regardless of treatment. Simultaneously, Daphnia magna body size and cumulative reproduction increased across generations while survival decreased. Though antibiotics did cause substantial changes to microbiome composition, the microbiome generally became similar to the no antibiotic control treatment within one generation of recovery no matter how many prior generations were spent in antibiotics. ConclusionsContrary to results found in vertebrate systems, Daphnia magna microbiome composition recovers quickly after antibiotic exposure. However, our results suggest that the isolation of individual hosts leads to the stochastic extinction of rare taxa in the microbiome, indicating that these taxa are likely maintained via transmission in host populations rather than intrinsic mechanisms. This may explain the intriguing result that microbiome diversity loss increased host fitness.

ecology↗

Inter-Subject EEG Correlation Reflects Time-Varying Engagement with Natural Music

Musical engagement can be conceptualized through various activities, modes of listening, and listener states--among these a state of focused engagement. Recent research has reported that this state can be indexed by the inter-subject correlation (ISC) of EEG responses to a shared naturalistic stimulus. While statistically significant ISC has been reported during music listening, these reports have considered only correlations computed across entire excerpts and do not provide insights into time-varying engagement. Here we present the first EEG-ISC investigation of time-varying engagement within a musical work. From a sample of 23 adult musicians who listened to a cello concerto movement, we find varying levels of ISC throughout the excerpt. In particular, significant ISC is observed during periods of musical tension that build to climactic highpoints, but not at the highpoints themselves. In addition, we find that a control stimulus retaining envelope characteristics of the intact music, but little other temporal structure, also elicits significant neural correlation, though to a lesser extent than the original excerpt. In all, our findings shed light on temporal dynamics of listener engagement during music listening, establish connections between salient musical events and EEG ISC, and clarify specific listener states that are indexed by this measure.

neuroscience↗

The ATF6β-calreticulin axis protects hippocampal neurons against endoplasmic reticulum stress and excitotoxicity

While ATF6 plays a central role in the endoplasmic reticulum (ER) stress response, the function of ATF6{beta} is largely unknown. Here, we demonstrate that ATF6{beta} is highly expressed in the hippocampus of the brain, and specifically regulates the expression of calreticulin, a molecular chaperone in the ER with a high Ca2+-binding capacity. Calreticulin expression was reduced to ~50% in the central nervous system of Atf6b-/- mice, and restored by ATF6{beta}. Analysis using cultured hippocampal neurons revealed that ATF6{beta} deficiency reduced Ca2+ stores in the ER and enhanced ER stress-induced death, which was rescued by ATF6{beta}, calreticulin, Ca2+-modulating reagents such as BAPTA-AM and 2-APB, and ER stress inhibitor salubrinal. In vivo, kainate-induced neuronal death was enhanced in hippocampi of Atf6b-/- and Calr+/- mice, and restored by 2-APB and salubrinal. These results suggest that the ATF6{beta}-calreticulin axis plays a critical role in the neuronal survival by improving Ca2+ homeostasis under ER stress.

cell biology↗

In vitro infection of human lung tissue with SARS-CoV-2: Heterogeneity in host defense and therapeutic response

Cell lines are the mainstay in understanding the biology of COVID-19 infection, but do not recapitulate many of the complexities of human infection. The use of human lung tissue is one solution for the study of such novel respiratory pathogens. We hypothesized that a cryopreserved bank of human lung tissue allows for the in vitro study of the inter-individual heterogeneity of host response to SARS-CoV-2 infection, thus providing a bridge between studies with cell lines and studies in animal models. We generated a cryobank of tissues from 16 donors, most of whom had risk factors for severe illness from COVID-19. Cryopreserved tissues preserved 90% of cell viability and contained heterogeneous populations of metabolically active epithelial, endothelial, and immune cell subsets of the human lung. Samples were readily infectible with HCoV-OC43 and SARS-CoV-2 coronavirus strains, and demonstrated comparable susceptibility to infection. In contrast, we observed a marked donor-dependent heterogeneity in the expression of IL-6, CXCL8 and IFN{beta} in response to SARS-CoV-2 infection. Treatment of tissues with dexamethasone and the experimental drug, N-hydroxycytidine, suppressed viral growth in all samples, whereas chloroquine and remdesivir had no detectable effect. Metformin and sirolimus, molecules with predicted antiviral activity, suppressed viral replication in tissues from a subset of donors. In summary, we developed a novel system for the in vitro study of human SARS-CoV-2 infection using primary human lung tissue from a library of donor tissues. This model may be useful for drug screening and for understanding basic mechanisms of COVID-19 pathogenesis. ImportanceThe current biological systems for the study of COVID-19 are in vitro systems that differ from the human lung in many respects, and animal hosts to which the virus is not adapted. We developed another alternative for studying pathogenesis and drug susceptibility of SARS-CoV-2 in a cryopreserved bank of human lung tissues. We consider the importance of this work to relate to the practical use of this culture system as a repeatable and scalable approach that allows for the study of an important infection in relevant tissues. The tissue bank highlights the heterogeneous response to SARS-CoV-2 infection and treatment, which allows researchers to investigate why treatments work in some donors but not others.

microbiology↗

Differential effects of amplitude-modulated transcranial focused ultrasound on excitatory and inhibitory neurons

Although stimulation with ultrasound has been shown to modulate brain activity at multiple scales, it remains unclear whether transcranial focused ultrasound stimulation (tFUS) exerts its influence on specific cell types. Here we propose a novel form of tFUS where a continuous waveform is amplitude modulated (AM) at a slow rate (i.e., 40 Hz) targeting the temporal range of electrophysiological activity: AM-tFUS. We stimulated the rat hippocampus while recording multi-unit activity (MUA) followed by classification of spike waveforms into putative excitatory pyramidal cells and inhibitory interneurons. At low acoustic intensity, AM-tFUS selectively reduced firing rates of inhibitory interneurons. On the other hand, higher intensity AM-tFUS increased firing of putative excitatory neurons with no effect on inhibitory firing. Interestingly, firing rate was unchanged during AM-tFUS at intermediate intensity. Consistent with the observed changes in firing rate, power in the theta band (3-10 Hz) of the local field potential (LFP) decreased at low-intensity, was unchanged at intermediate intensity, and increased at higher intensity. Temperature increases at the AM-tFUS target were limited to 0.2{degrees}C. Our findings indicate that inhibitory interneurons exhibit greater sensitivity to ultrasound, and that cell-type specific neuromodulation may be achieved by calibrating the intensity of AM-tFUS.

neuroscience↗

CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signalling to promote expansion of cortical progenitors.

The primary cilum is a central component of signalling during neural development, from regional patterning to neuronal differentiation. Here we focus on CROCCP2, a hominid-specific gene duplicate from CROCC (Ciliary Rootlet Coiled Coil), also known as rootletin, that encodes the major protein component of the ciliary rootlet. We find that CROCCP2 is highly expressed in the human fetal brain and not in other primate species. CROCCP2 gain of function in the mouse embryonic cortex results in decreased ciliogenesis, increased mTOR signalling, and increased cell size of radial glial cells, leading to increased generation of intermediate/basal progenitors and increased neuronal output. CROCCP2 impacts cilia dynamics and neurogenesis by inhibition of the IFT20 ciliary trafficking protein. Our data identify a human-specific protein that drives cortical basal progenitor expansion through modulation of ciliary dynamics.

neuroscience↗

Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence

Origin of the COVID-19 virus (SARS-CoV-2) has been intensely debated in the scientific community since the first infected cases were detected in December 2019. The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the hosts for SARS-CoV-2 based on comparative studies using its genomic sequences. This paper investigates the SARS-CoV-2 origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined SARS-CoV-2 genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidence strongly supporting scientific hypotheses that bats and pangolins are probable hosts for SARS-CoV-2. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins.

bioinformatics↗

Prostaglandin receptor EP2 is a novel molecular target for high-risk neuroblastoma

As the third-most common type of cancers in infants and young children, neuroblastoma accounts for nearly 10% of all childhood cancers. Despite remarkable advances in tumor diagnosis and management during the past decades, the five-year survival rates for patients with high-risk neuroblastoma remain below 50%. Developing new therapies for this devastating type of childhood cancer is an urgent unmet need. Cyclooxygenase (COX) via synthesizing prostaglandin E2 (PGE2) promotes tumor cell proliferation, survival, migration and invasion, and fosters an inflammation-enriched microenvironment that can facilitate angiogenesis, immune evasion and treatment resistance. However, which downstream PGE2 receptor subtype - namely EP1, EP2, EP3 and EP4 - is directly involved in COX activity-promoted neuroblastoma growth remains elusive. Analyzing five major neuroblastoma patient datasets: Versteeg-88, Kocak-649, SEQC-498, Primary NRC-283, and Oberthuer-251, we show that COX-1/PGE2/EP2 signaling axis is highly associated with the aggressiveness of human neuroblastoma. A time-resolved fluorescence resonance energy transfer (TR-FRET) method reveals EP2 as the key Gs-coupled receptor that mediates PGE2-initiated cAMP signaling in neuroblastoma cells with various risk factors. Taking advantage of novel, selective and bioavailable small-molecule antagonists that we recently developed to target the PGE2/EP2 signaling in vivo, we have demonstrated that pharmacological inhibition of the peripheral EP2 receptor substantially impairs the growth of human neuroblastoma xenografts and the associated angiogenesis in mice. Collectively, our results suggest that the PGE2/EP2 pathway contributes to the growth and malignant potential of human neuroblastoma cells; pharmacological inhibition on EP2 receptor by our drug-like compounds might provide a novel therapeutic strategy for this deadly pediatric cancer.

pharmacology and toxicology↗

The paternal and maternal genetic history of Vietnamese populations

Vietnam exhibits great cultural and linguistic diversity, yet the genetic history of Vietnamese populations remains poorly understood. Previous studies focused mostly on the majority Kinh group, and thus the genetic diversity of the many other groups has not yet been investigated. Here we analyze complete mtDNA genome sequences and 2.34 mB sequences of the male-specific portion of the Y chromosome from the Kinh and 16 minority populations, encompassing all five language families present in Vietnam. We find highly variable levels of diversity within and between groups that do not correlate with either geography or language family. In particular, the Mang and Sila have undergone recent, independent bottlenecks, while the majority group, Kinh, exhibits low levels of differentiation with other groups. The two Austronesian-speaking groups, Giarai and Ede, show a potential impact of matrilocality on their patterns of variation. Overall, we find that isolation, coupled with some limited contact involving some groups, has been the major factor influencing the genetic structure of Vietnamese populations, and that there is substantial genetic diversity that is not represented by the Kinh.

genetics↗

Natural Music Evokes Correlated EEG Responses Reflecting Temporal Structure and Beat

The brain activity of multiple subjects has been shown to synchronize during salient moments of natural stimuli, suggesting that correlation of neural responses indexes a brain state operationally termed engagement. While past electroencephalography (EEG) studies have considered both auditory and visual stimuli, the extent to which these results generalize to music--a temporally structured stimulus for which the brain has evolved specialized circuitry--is less understood. Here we investigated neural correlation during natural music listening by recording dense-array EEG responses from N = 48 adult listeners as they heard real-world musical works, some of which were temporally disrupted through shuffling of short-term segments (measures), reversal, or randomization of phase spectra. We measured neural correlation across responses (inter-subject correlation) and between responses and stimulus envelope fluctuations (stimulus-response correlation) in the time and frequency domains. Stimuli retaining basic musical features evoked significantly correlated neural responses in all analyses. However, while unedited songs were self-reported as most pleasant, time-domain correlations were highest during measure-shuffled versions. Frequency-domain measures of correlation (coherence) peaked at frequencies related to the musical beat, although the magnitudes of these spectral peaks did not explain the observed temporal correlations. Our findings show that natural music evokes significant inter-subject and stimulus-response correlations, and suggest that the neural correlates of musical engagement may be distinct from those of enjoyment.

neuroscience↗

Human induced pluripotent stem cell-derived neuroectodermal epithelial cells mistaken for blood-brain barrier-forming endothelial cells

Brain microvascular endothelial cells (BMECs) possess unique properties underlying the blood-brain-barrier (BBB), that are crucial for homeostatic brain functions and interactions with the immune system. Modulation of BBB function is essential for treatment of neurological diseases and effective tumor targeting. Studies to-date have been hampered by the lack of physiological models using cultivated human BMECs that sustain BBB properties. Recently, differentiation of induced pluripotent stem cells (iPSCs) into cells with BBB-like properties has been reported, providing a robust in vitro model for drug screening and mechanistic understanding of neurological diseases. However, the precise identity of these iBMECs remains unclear. Employing single-cell RNA sequencing, bioinformatic analysis and immunofluorescence for several pathways, transcription factors (TFs), and surface markers, we examined the molecular and functional properties of iBMECs differentiated either in the absence or presence of retinoic acid. We found that iBMECs lack both endothelial-lineage genes and ETS TFs that are essential for the establishment and maintenance of EC identity. Moreover, iBMECs fail to respond to angiogenic stimuli and form lumenized vessels in vivo. We demonstrate that human iBMECs are not barrier-forming ECs but rather EpCAM+ neuroectodermal epithelial cells (NE-EpiCs) that form tight junctions resembling those present in BBB-forming BMECs. Finally, overexpression of ETS TFs (ETV2, FLI1, and ERG) reprograms NE-EpiCs to become more like the BBB-forming ECs. Thus, although directed differentiation of human iBMECs primarily gives rise to epithelial cells, overexpression of several ETS TFs can divert them toward a vascular BBB in vitro.

cell biology↗

A Novel Melatonergic Signature Predicts Reccurence Risk and Therapeutic Response in Breast Cancer Patients

ASMT is a key determinant of the levels of released melatonin. Though melatonin has been shown to exhibit anti-cancer activity and prevents endocrine resistance in breast cancer, the role of ASMT in breast cancer progression remains unclear. In this retrospective study, we analyzed gene expression profiles from thousands of patients and found that ASMT expression was significantly lower in breast cancer tumors relative to healthy tissue. Among cancer patients, those with greater expression had better relapse-free survival outcomes and longer metastasis-free survival times, and they also experienced longer periods before relapse or distance recurrence following tamoxifen treatment. Administration of melatonin, in combination with tamoxifen, further promoted cancer cell death by promoting apoptosis. Motivated by these results, we devised an ASMT gene signature that identifies low-risk cases with great accuracy. This signature was validated using both mRNA array and RNAseq datasets. Intriguingly, patients who are classified as high-risk benefit from adjuvant chemotherapy, and those with grade II tumors who are classified as low-risk exhibit improved overall survival and distance relapse-free outcomes following endocrine therapy. Our findings more clearly elucidate the roles of ASMT, provide strategies for improving the efficacy of tamoxifen treatment, and help to identify those patients who may maximally benefit from adjuvant or endocrine therapies.

cancer biology↗

Knowledge, Attitudes and Practices of Hepatitis B Prevention and Immunization of Pregnant Women and Mothers in Viet Nam

Background and AimVietnams high burden of liver cancer is largely attributable to the high prevalence of chronic hepatitis B virus infection (HBV). Infection at birth due to mother-to-child (MTC) transmission is the most common cause of chronic HBV in Vietnam and increases the risk of liver cancer later in life. This study was undertaken to examine the knowledge, attitudes, and practices of pregnant women and mothers in Vietnam concerning HBV prevention and immunization.\n\nMethodsA cross-sectional study was conducted in Quang Ninh and Hoa Binh provinces in 2017. A pre-designed questionnaire was administered to women when they received care at primary and tertiary maternal health clinics. Correct responses were summarized as knowledge scores. Data was analyzed using a multivariable regression model across participant demographics.\n\nResultsAmong the 404 women surveyed, 57.6% were pregnant and 42.4% were postpartum. Despite 73.5% of participants reporting having received information about HBV during their pregnancy, gaps in knowledge and misconceptions are evident. Overall, only 10.6% provided correct answers to all questions regarding HBV transmission routes and prevention measures. Around half of the participants incorrectly believed that HBV is transmitted through sneezing, contaminated water or sharing foods with chronic HBV patients. Although 96.4% of participants believed that HBV vaccination is necessary for infants, only 69.1% were willing to have their own child vaccinated within 24 hours. More than a third of participants expressed concern about having casual contacts or sharing foods with chronic HBV patients. In multivariable analysis, having received information about HBV during their pregnancy were consistently associated with better knowledge score for transmission, prevention and immunization. However, knowledge of women who received information about HBV during their pregnancy was still suboptimal.\n\nConclusionsThe results highlight the need to prioritize educating pregnant women and mothers in future public health campaigns in order to increase knowledge, reduce misperception, and improve HBV vaccine coverage in Vietnam.

epidemiology↗