The SWI/SNF Complex: A Frequently Mutated Chromatin Remodeling Complex in Cancer.

The switch/sucrose non-fermenting (SWI/SNF) chromatin remodeling complex is a global regulator of gene expression known to maintain nucleosome-depleted regions at active enhancers and promoters. The mammalian SWI/SNF protein subunits are encoded by 29 genes and 11-15 subunits including an ATPase domain of either SMARCA4 (BRG1) or SMARCA2 (BRM) are assembled into a complex. Based on the distinct subunits, SWI/SNF are grouped into 3 major types (subfamilies): the canonical BRG1/BRM-associated factor (BAF/cBAF), polybromo-associated BAF (PBAF), and non-canonical BAF (GBAF/ncBAF). Pan-cancer genome sequencing studies have shown that nearly 25% of all cancers bear mutations in subunits of the SWI/SNF complex, many of which are loss of function (LOF) mutations, suggesting a tumor suppressor role. Inactivation of SWI/SNF complex subunits causes widespread epigenetic dysfunction, including increased dependence on antagonistic components such as polycomb repressor complexes (PRC1/2) and altered enhancer regulation, likely promoting an oncogenic state leading to cancer. Despite the prevalence of mutations, most SWI/SNF-mutant cancers lack targeted therapeutic strategies. Defining the dependencies created by LOF mutations in SWI/SNF subunits will identify better targets for these cancers.

An improvement of real-time polymerase chain reaction system based on probe modification is required for accurate detection of African swine fever virus in clinical samples in Vietnam.

OBJECTIVE: The rapid and reliable detection of the African swine fever virus (ASFV) plays an important role in emergency control and preventive measures of ASF. Some methods have been recommended by FAO/OIE to detect ASFV in clinical samples, including realtime polymerase chain reaction (PCR). However, mismatches in primer and probe binding regions may cause a false-negative result. Here, a slight modification in probe sequence has been conducted to improve the qualification of real-time PCR based on World Organization for Animal Health (OIE) protocol for accurate detection of ASFV in field samples in Vietnam. METHODS: Seven positive confirmed samples (four samples have no mismatch, and three samples contained one mutation in probe binding sites) were used to establish novel real-time PCR with slightly modified probe (Y = C or T) in comparison with original probe recommended by OIE. RESULTS: Both real-time PCRs using the OIE-recommended probe and novel modified probe can detect ASFV in clinical samples without mismatch in probe binding site. A high correlation of cycle quantification (Cq) values was observed in which Cq values obtained from both probes arranged from 22 to 25, suggesting that modified probe sequence does not impede the qualification of real-time PCR to detect ASFV in clinical samples. However, the samples with one mutation in probe binding sites were ASFV negative with OIE recommended probe but positive with our modified probe (Cq value ranked between 33.12-35.78). CONCLUSION: We demonstrated for the first time that a mismatch in probe binding regions caused a false negative result by OIE recommended real-time PCR, and a slightly modified probe is required to enhance the sensitivity and obtain an ASF accurate diagnosis in field samples in Vietnam.

Utilizing Predictive Factors as a Screening Tool for Early-Onset Sepsis in Neonates.

INTRODUCTION: Neonatal early-onset sepsis (EOS) is a severe condition that affects newborns within the first three days of life, with high mortality rates, particularly in low- and middle-income countries (LMICs). In Vietnam, the diagnosis and management of EOS are challenged by ambiguous clinical signs and limited access to blood culture testing facilities. Early identification of at-risk neonates using a predictive risk factor model is crucial for improving neonatal care and reducing mortality. OBJECTIVES: This study aims to identify maternal and neonatal risk factors associated with EOS and develop a predictive screening tool to facilitate the early detection of at-risk neonates in Vietnam. MATERIALS AND METHODS: A nested case-control study was conducted on 225 neonates at the central neonatal unit in a principal tertiary hospital in southwestern Vietnam over a two-year period. Risk factors were identified using univariable and multivariable logistic regression analyses. A predictive nomogram was developed and evaluated for discrimination, calibration, and decision curve analysis (DCA). RESULTS: The study identified eight significant risk factors for EOS, including maternal genital infections during the third trimester, urinary tract infections (UTIs) during pregnancy, hypertension during pregnancy, insufficient maternal weight gain, rupture of membranes (ROM) ≥18 hours, meconium-stained amniotic fluid, first-minute APGAR score <7, and preterm birth <34 weeks. The predictive model demonstrated excellent discrimination with an area under the curve (AUC) of 0.913 (95% CI: 0.876-0.95, p<0.001) and good calibration (Hosmer-Lemeshow test with χ²(df)=5.496 (5), p=0.358). The model-based nomogram showed high sensitivity (82.7%) and specificity (83.3%) at an optimal cutoff of 0.25. The DCA illustrates the model's good clinical utility, providing a higher net benefit across most threshold probability ranges (0.0-0.96). CONCLUSIONS: This study presents a robust predictive model for the early identification of neonates at risk of EOS in Vietnam, based on key maternal and neonatal risk factors. The model, with demonstrated accuracy and reliability, holds significant potential for improving neonatal outcomes through timely interventions. Future research should aim at external validation and inclusion of broader clinical data to enhance the model's applicability and generalizability.

A new variant of lumpy skin disease virus circulating in Vietnam based on sequencing analysis of GPCR gene.

Background: In 2021, Vietnam experienced an outbreak of Lumpy skin disease (LSD), which infected 207,687 cattle and buffaloes, as officially reported, and resulted in the culling of 29,182 animals. Aim: In this study, samples from cattle that died and showed typical signs of LSD in the Ha Tinh province of Vietnam were confirmed by three World Organization for Animal Health (WOAH)-recommended methods and further studied to compare the Vietnam and China reference strains to the new clinical cases. Methods: Three methods recommended by WOAH for agent detection (PCR, virus isolation, and transmission electron microscopy) were used to confirm this clinical LSD case. The sequence analysis of three well-known markers (P32, RPO30, and GPCR genes) has been utilized in Vietnam to understand this circulating pathogen better. Results: Our findings showed that the CX01 LSDV strain is 100% identical to the Vietnam reference strain HL01 and China reference strains based on P32 and RPO30 genes. Interestingly, analysis of the nucleotide sequence of the GPCR gene showed that the CX01 strain belongs to the same cluster as the reference strains, but it has branches different from those of both the HL01 and China LSDV strains. The nucleotide identification between the CX01 strain and these reference virus strains ranked 99.65%-99.91%, suggesting that it is a new variant of LSDV. Conclusion: This finding is new and indicates that at least two variants of the LSD virus were circulating in Vietnam based on analysis of the GPCR gene. Additionally, these results suggest that the sequence analysis of the GPCR gene is a great tool for subgrouping LSDV circulating in Vietnam.

Lumpy skin disease outbreaks in vietnam, 2020.

Lumpy skin disease (LSD) is a transboundary, systemic, viral disease of cattle. The first outbreaks of LSD were reported in Lang Son Province of Vietnam (bordered to China), and an official document has been submitted to OIE on 1 November 2020. Here, we described first the genetic profiles of this pathogen based on four well-known marker regions. The LSD virus isolated in these first outbreaks was 100% identical to viruses isolated in China (2019) based on the p32 and RP030 genes. Additionally, it is very close to the virus isolated in Russia (2017) based on the p32, RP030, thymidine kinase and ORF103 genes (100%, 99.01%, 99.08% and 99.47% identities). This finding is new, and a success in LSD virus isolation using MDBK cells from first outbreaks is important for vaccine development to control and eradicate LSD in Vietnam.

High-Resolution HLA Typing of HLA-A, -B, -C, -DRB1, and -DQB1 in Kinh Vietnamese by Using Next-Generation Sequencing.

Human leukocyte antigen (HLA) genotyping displays the particular characteristics of HLA alleles and haplotype frequencies in each population. Although it is considered the current gold standard for HLA typing, high-resolution sequence-based HLA typing is currently unavailable in Kinh Vietnamese populations. In this study, high-resolution sequence-based HLA typing (3-field) was performed using an amplicon-based next-generation sequencing platform to identify the HLA-A, -B, -C, -DRB1, and -DQB1 alleles of 101 unrelated healthy Kinh Vietnamese individuals from southern Vietnam. A total of 28 HLA-A, 41 HLA-B, 21 HLA-C, 26 HLA-DRB1, and 25 HLA-DQB1 alleles were identified. The most frequently occurring HLA alleles were A∗11:01:01, B∗15:02:01, C∗07:02:01, DRB1∗12:02:01, and DQB1∗03:01:01. Haplotype calculation showed that A∗29:01:01∼B∗07:05:01, DRB1∗12:02:01∼DQB1∗3:01:01, A∗29:01:01∼C∗15:05:02∼B∗07:05:01, A∗33:03:01∼B∗58:01:01∼DRB1∗03:01:01, and A∗29:01:01∼C∗15:05:02∼B∗07:05:01∼DRB1∗10:01:01∼DQB1∗05:01:01 were the most common haplotypes in the southern Kinh Vietnamese population. Allele distribution and haplotype analyses demonstrated that the Vietnamese population shares HLA features with South-East Asians but retains unique characteristics. Data from this study will be potentially applicable in medicine and anthropology.

The potential efficacy of the E2-subunit vaccine to protect pigs against different genotypes of classical swine fever virus circulating in Vietnam.

PURPOSE: To date, many kinds of classical swine fever (CSF) vaccines have been developed to protect against this disease. However, the efficacy of these vaccines to protect the pig against field CSF strains needs to be considered, based on circulating strains of classical swine fever virus (CSFV). MATERIALS AND METHODS: Recombinant E2-CSFV protein produced by baculovirus/insect cell system was analyzed by western blots and immunoperoxidase monolayer assay. The effect of CSFV-E2 subunit vaccines was evaluated in experimental pigs with three genotypes of CSFV challenge. Anti-E2 specific and neutralizing antibodies in experimental pigs were analyzed by blocking enzyme-linked immunosorbent assay and neutralization peroxidize-linked assay. RESULTS: The data showed that CSFV VN91-E2 subunit vaccine provided clinical protection in pigs against three different genotypes of CSFV without noticeable clinical signs, symptoms, and mortality. In addition, no CSFV was isolated from the spleen of the vaccinated pigs. However, the unvaccinated pigs exhibited high clinical scores and the successful virus isolation from spleen. These results showed that the E2-specific and neutralizing antibodies induced by VN91-E2 antigen appeared at day 24 after first boost and a significant increase was observed at day 28 (p<0.01). This response reached a peak at day 35 and continued until day 63 when compared to controls. Importantly, VN91-E2 induced E2-specific and neutralizing antibodies protected experimental pigs against high virulence of CSFVs circulating in Vietnam, including genotype 1.1, 2.1, and 2.2. CONCLUSION: These findings also suggested that CSFV VN91-E2 subunit vaccine could be a promising vaccine candidate for the control and prevention of CSFV in Vietnam.