A complete temporal transcription factor series in the fly visual system.

The brain consists of thousands of neuronal types that are generated by stem cells producing different neuronal types as they age. In Drosophila, this temporal patterning is driven by the successive expression of temporal transcription factors (tTFs)1-6. Here we used single-cell mRNA sequencing to identify the complete series of tTFs that specify most Drosophila optic lobe neurons. We verify that tTFs regulate the progression of the series by activating the next tTF(s) and repressing the previous one(s), and also identify more complex mechanisms of regulation. Moreover, we establish the temporal window of origin and birth order of each neuronal type in the medulla and provide evidence that these tTFs are sufficient to explain the generation of all of the neuronal diversity in this brain region. Finally, we describe the first steps of neuronal differentiation and show that these steps are conserved in humans. We find that terminal differentiation genes, such as neurotransmitter-related genes, are present as transcripts, but not as proteins, in immature larval neurons. This comprehensive analysis of a temporal series of tTFs in the optic lobe offers mechanistic insights into how tTF series are regulated, and how they can lead to the generation of a complete set of neurons.

Experience of Autologous Immunotherapy for Non-Small Cell Lung Cancer Using Zoledronate-Actived Gammadelta T Cells.

BACKGROUND: Several nations around the world have utilized autologous immune enhancement therapy in the treatment of cancer, with initial positive outcomes. This study describes our experience with autologous gamma delta T cell immunotherapy for the treatment of non-small cell lung cancer patients in Vietnam, a developing nation. METHODS: Five patients with non-small cell lung cancer at stages III - IV were enrolled in the study. Each patient received six infusions of autologous γδT cells, separated by two weeks. Before, during, at the end of treatment, and three and six months after treatment, a comprehensive evaluation of clinical, laboratory, quality of life, and adverse events related to the method was conducted. RESULTS: At the time of culture seeding, the total number of cells ranged from 2.9 to 18.2 x 106, with γδT cells ranging in number from 10.7 to 19.6 x 104. On day 14 of the culture, the number of γδT cells ranged from 3.1 to 8.3 x 108. Regarding the safety of therapy in a total of 30 infusions, two (fever), one (myalgia), and one (joint pain) were graded as 1 by CTCAE criteria. After the course, no toxicity was observed in the hematopoietic system, kidney function, or liver function. Evaluation of the patient's response in accordance with the RECIST 1.1 criteria: 20% of patients (one patient) had partial response disease, and 80% of patients (four patients) had stable disease at the end of treatment. During the follow-up period of the study, three patients were still alive, and the disease remained stable. The patient's quality of life improved after treatment in most functional measures (activity, cognitive, and social), but physical and emotional scores decreased slightly. Two patients' fatigue symptoms increased, but after six months of treatment, the average value dropped from 25.3 to 8.3. Dyspnea symptoms decreased gradually from 33.3 at the start of treatment to 8.3 six months later. CONCLUSIONS: The initial results we obtained regarding the efficacy and safety of autologous γδT cell immunotherapy for patients with non-small cell lung cancer are extremely encouraging and comparable to those of previous studies.

Pediatric Profound Dengue Shock Syndrome and Use of Point-of-Care Ultrasound During Mechanical Ventilation to Guide Treatment: Single-Center Retrospective Study, 2013-2021.

OBJECTIVES: Profound dengue shock syndrome (DSS) complicated by severe respiratory failure necessitating mechanical ventilation (MV) accounts for high case fatality rates among PICU-admitted patients. A major challenge to management is the assessment of intravascular volume, which can be hampered by severe plasma leakage and the use of MV. DESIGN: Retrospective cohort, from 2013 to 2021. PATIENTS: Sixty-seven children with profound DSS supported by MV, some of whom underwent bedside point-of-care ultrasound (POCUS) for assessment and monitoring of hemodynamics and fluid administration. SETTING: PICU of the tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data clinical and laboratory data during PICU stay. In particular, during use of MV (i.e., at times 0-, 6-, and 24-hr after commencement) and fluid resuscitation. The primary study outcome was 28-day in-hospital mortality, and the secondary outcomes were associations with changes in hemodynamics, blood lactate, and vasoactive-inotrope score (VIS). Patients had a median age of 7 years (interquartile range, 4-9). Use of POCUS during fluid management (39/67), as opposed to not using (28/67), was associated with lower mortality (6/39 [15%] vs. 18/28 [64%]; difference 49 % [95% CI, 28-70%], p < 0.001). Use of POCUS was associated with lower odds of death (adjusted odds ratio 0.17 [95% CI, 0.04-0.76], p = 0.02). The utilization of POCUS, versus not, was associated with greater use of resuscitation fluid, and reductions in VIS and pediatric logistic organ dysfunction (PELOD-2) score at 24 hours after MV and PICU discharge. CONCLUSIONS: In our experience of pediatric patients with profound DSS and undergoing MV (2013-2021), POCUS use was associated with lower odds of death, a higher volume of resuscitation fluid, and improvements in the blood lactate levels, VIS, and PELOD-2 score.

New species of the eel genera Dysomma and Dysommina from Vietnam, South China Sea (Anguilliformes: Synaphobranchidae).

Two new cutthroat eel species are described from Vietnam. Dysomma intermedium sp. nov. has a relatively long trunk, being about half of head length and anal-fin origin more than twice pectoral-fin length behind the pectoral-fin tip; pectoral fin well developed; dorsal-fin origin over or slightly in front of base of pectoral fin; two intermaxillary teeth; four or five compound teeth on ethmovomer; single row of seven or eight teeth on lower jaw; total lateral-line pores 70-76; and 21 pre-anal and 118-124 total vertebrae. Dysommina brevis sp. nov. differs from congeners by having a trunk shorter than head length, its length 11.1%-11.8% TL; a short pre-anal length 24.6%-25.6% TL, eye diameter 11.8%-12.3% head length; three large and one or two small teeth on ethmovomer; and fewer teeth on the upper and lower jaws. In addition, a specimen representing the first record of Dysommina orientalis in Vietnamese water is documented.

B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers.

Activation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes, among other genes. We investigated the transcriptional regulation of Aicda (which encodes AID) in class switch-inducible CH12F3-2 cells and found that Aicda regulation involved derepression by several layers of positive regulatory elements in addition to the 5' promoter region. The 5' upstream region contained functional motifs for the response to signaling by cytokines, the ligand for the costimulatory molecule CD40 or stimuli that activated the transcription factor NF-kappaB. The first intron contained functional binding elements for the ubiquitous silencers c-Myb and E2f and for the B cell-specific activator Pax5 and E-box-binding proteins. Our results show that Aicda is regulated by the balance between B cell-specific and stimulation-responsive elements and ubiquitous silencers.

Investigation of target sequencing of SARS-CoV-2 and immunogenic GWAS profiling in host cells of COVID-19 in Vietnam.

BACKGROUND: A global pandemic has been declared for coronavirus disease 2019 (COVID-19), which has serious impacts on human health and healthcare systems in the affected areas, including Vietnam. None of the previous studies have a framework to provide summary statistics of the virus variants and assess the severity associated with virus proteins and host cells in COVID-19 patients in Vietnam. METHOD: In this paper, we comprehensively investigated SARS-CoV-2 variants and immune responses in COVID-19 patients. We provided summary statistics of target sequences of SARS-CoV-2 in Vietnam and other countries for data scientists to use in downstream analysis for therapeutic targets. For host cells, we proposed a predictive model of the severity of COVID-19 based on public datasets of hospitalization status in Vietnam, incorporating a polygenic risk score. This score uses immunogenic SNP biomarkers as indicators of COVID-19 severity. RESULT: We identified that the Delta variant of SARS-CoV-2 is most prevalent in southern areas of Vietnam and it is different from other areas in the world using various data sources. Our predictive models of COVID-19 severity had high accuracy (Random Forest AUC = 0.81, Elastic Net AUC = 0.7, and SVM AUC = 0.69) and showed that the use of polygenic risk scores increased the models' predictive capabilities. CONCLUSION: We provided a comprehensive analysis for COVID-19 severity in Vietnam. This investigation is not only helpful for COVID-19 treatment in therapeutic target studies, but also could influence further research on the disease progression and personalized clinical outcomes.

Enhanced Emission from Interlayer Excitons Coupled to Plasmonic Gap Cavities.

The emergence of interlayer excitons (IEs) from atomic layered transition metal dichalcogenides (TMDCs) heterostructures has drawn tremendous attention due to their unique and exotic optoelectronic properties. Coupling the IEs into optical cavities provides distinctive electromagnetic environments which plays an important role in controlling multiple optical processes such as optical nonlinear generation or photoluminescence enhancement. Here, the integration of IEs in TMDCs into plasmonic nanocavities based on a nanocube on a metallic mirror is reported. Spectroscopic studies reveal an order of magnitude enhancement of the IE at room temperature and a 5-time enhancement in fluorescence at cryogenic temperatures. Cavity modeling reveals that the enhancement of the emission is attributed to both increased excitation efficiency and Purcell effect from the cavity. The results show a novel method to control the excitonic processes in TMDC heterostructures to build high performance photonics and optoelectronics devices.

Tempora: Cell trajectory inference using time-series single-cell RNA sequencing data.

Single-cell RNA sequencing (scRNA-seq) can map cell types, states and transitions during dynamic biological processes such as tissue development and regeneration. Many trajectory inference methods have been developed to order cells by their progression through a dynamic process. However, when time series data is available, most of these methods do not consider the available time information when ordering cells and are instead designed to work only on a single scRNA-seq data snapshot. We present Tempora, a novel cell trajectory inference method that orders cells using time information from time-series scRNA-seq data. In performance comparison tests, Tempora inferred known developmental lineages from three diverse tissue development time series data sets, beating state of the art methods in accuracy and speed. Tempora works at the level of cell clusters (types) and uses biological pathway information to help identify cell type relationships. This approach increases gene expression signal from single cells, processing speed, and interpretability of the inferred trajectory. Our results demonstrate the utility of a combination of time and pathway information to supervise trajectory inference for scRNA-seq based analysis.

Mechanism for the Binding of Netropsin to Hairpin DNA Revealed Using Nanoscale Ion Emitters in Native Mass Spectrometry.

Netropsin is one of the first ligands to be discovered that selectively binds to the minor groove of DNA and is actively used as a scaffold for developing potential anticancer and antibiotic agents. The mechanism by which netropsin binds to hairpin DNA remains controversial with two competing mechanisms having been proposed. In one mechanism, netropsin binding induces a hairpin-to-duplex DNA transition. Alternatively, netropsin binds in two thermodynamically different modes at a single duplexed AATT site. Here, results from native mass spectrometry (MS) with nanoscale ion emitters indicate that netropsin can simultaneously and sequentially bind to both hairpin and duplex DNA. Duplex DNA was not detected using conventional MS with larger emitters because nanoscale emitters significantly reduce the extent of salt adduction to ligand-DNA complex ions, including in the presence of relatively high concentrations of nonvolatile salts. Based on native MS and polyacrylamide gel electrophoresis results, the abundances of hairpin and duplex DNA are unaffected by the addition of netropsin. By native MS, the binding affinities for five ligand-DNA and DNA-DNA interactions can be rapidly obtained simultaneously. This research indicates a "simultaneous binding mechanism" for the interactions of netropsin with DNA.

A Single Chiral Nanoparticle Induced Valley Polarization Enhancement.

Valley polarization is among the most critical attributes of atomically thin materials. However, increasing contrast from monolayer transition metal dichalcogenides (TMDs) has so far been challenging. In this work, a large degree of circular polarization up to 45% from a monolayer WS2 is achieved at room temperature by using a single chiral plasmonic nanoparticle. The increased contrast is attributed to the selective enhancement of both the excitation and the emission rate having one particular handedness of the circular polarization, together with accelerated radiative recombination of valley excitons due to the Purcell effect. The experimental results are corroborated by the optical simulation using the finite-difference time-domain (FDTD) method. Additionally, the single chiral nanoparticle enables the observation of valley-polarized luminescence with a linear excitation. The results provide a promising pathway to enhance valley contrast from monolayer TMDs and utilize them for nanophotonic devices.

A Novel Nonsense Mutation c.374C>G in CYP21A2 Gene of a Vietnamese Patient with Congenital Adrenal Hyperplasia.

Inactivating mutations of the CYP21A2 gene, encoding for steroid synthesis, have been reported in patients with congenital adrenal hyperplasia (CAH). We report a case of an infant who were diagnosed with CAH and presented with the severe phenotype of CAH with symptoms such as increased testicular volume, elevated of 17-hydroxyprogesteron, testosterone and progesterone. In this study, we established an assay for the detection of unusual genetic in the CYP21A2 gene in the proband and his family. A novel nonsense mutation c.374C > G which caused a substitutions of Serine for a stop codon at codon 125 (p.S125*) within exon 3 was found in the proband. Parental genotype studies confirmed carrier state in the father, but the mother showed a wild allele by PCR and sequencing. This inspired us to find deletions using multiplex ligation-dependent probe amplification (MLPA) technique. The probands were found to have a large deletion in exons 1 and 3, while the mother only had deletion in exon 1. Therefore, mutation c.374C > G (p.S125*) in the proband is considered as a heterozygous deletion. This mutation caused a truncated protein which lead to the salt wasting CAH phenotype of the proband. This novel nonsense mutation expands the CYP21A2 mutation spectrum in CAH disorder. This case also highlights the need of caution when interpreting results of molecular genetic testing during genetic counseling.

Variation of Mitochondrial DNA HV1 AND HV2 of the Vietnamese Population.

BACKGROUND: The sequence polymorphism of mitochondrial DNA (mtDNA) hypervariable segment 1 (HV1) and hypervariable segment 2 (HV2) is studied and applied to genetic diversity and human evolution assessment, forensic genetics, consanguinity determination, and mitochondrial disease diagnosis. METHODS: The study identified the variations of HV1 and HV2 of 517 unrelated Vietnamese individuals in Kinh, Muong, Cham, and Khmer ethnic. We performed sequencing of two hypervariable segments of mitochondrial DNA: HV1 and HV2. RESULTS: Fifty haplogroups were identified in which F1a haplogroup frequency was highest at 15.7%, followed by B5a (10.8%), M (8.9%), and M7b1 (7.7%). The most frequently encountered SNPs in this study were A263G (100%), A73G (99.6%), 315insC (96%), 309insC (56%), C16223T (41%), and T16189C (39%). The genetic diversity was calculated at 99.83%, and the probability of random match of two individuals sharing the same mtDNA haplotype was 0.37%. CONCLUSION: We have assessed the genetic polymorphism of mtDNA HV1 and HV2 of 517 Kinh, Muong, Cham, and Khmer ethnic samples. The result will help in better understanding of Vietnamese's mitochondrial genome diversity and aid in population as well as forensic science.

A case of self-improving collodion ichthyosis in Vietnam.

Autosomal recessive congenital ichthyosis is a heterogeneous group of congenital disorders characterized by aberrant skin cornification and diffuse skin scaling. Some patients with this condition are born encased in a collodion membrane which is later shed, revealing the underlying skin disorder. Self-healing collodion baby (SHCB) is a less common phenotype of this disorder, accounting for about 10% of the patients, in which the membrane peels after several weeks, leaving no underlying skin aberration. Here, we report and discuss the diagnosis and management of an infant with SHCB in Vietnam due to compound heterozygous pathogenic mutations in TGM1.

Acromesomelic dysplasia Maroteaux-type in patients from Vietnam.

Acromesomelic dysplasias are rare skeletal disorders leading to severe short stature and abnormal skeletal morphology. Acromesomelic dysplasia Maroteaux-type is caused by homozygous or compound heterozygous pathogenic variants in NPR2 that encodes for natriuretic peptide receptor B. Here, we reported the first AMDM case in South East Asia and identified a novel pathogenic variant in NPR2 (c. 152T>C, p. (Leu51Pro)). Further analyses reveal the parents and two other family members were heterozygous for the variant. The clinical report highlights the importance of molecular genetic testing in diagnosing rare hereditable disease affecting skeletal abnormalities.

Beyond BMI: The "Metabolically healthy obese" phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic review.

BACKGROUND: A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population. METHODS: Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD. RESULTS: A total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define "metabolically healthy", while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts. CONCLUSIONS: MHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.

Health-state utility of patients with HER2-positive breast cancer in Vietnam: A multicenter cross-sectional study.

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer may have poor prognoses and short overall and disease-free survival. Most previous studies focused on assessing the quality of life and health-state utility of the general population of breast cancer patients. The number of studies for HER2-positive breast cancer patients is negligible. This study investigated the health-state utility and its associated factors among Vietnamese patients with HER2-positive breast cancer. METHODS: We conducted face-to-face interviews with 301 HER2-positive breast cancer patients to collect data. Their health-state utility was measured via the EQ-5D-5L instrument. The Mann-Whitney U and Kruskal-Wallis tests were employed to compare the differences in utility scores between two groups and among three groups or more, respectively. Factors associated with patients' heath-state utility were identified via Tobit regression models. RESULTS: Pain/discomfort (56.1%) and anxiety/depression (39.5%) were the two issues that patients suffered from the most, especially among metastatic breast cancer patients. The severity of distress (depression, anxiety, and stress) in patients was relatively mild. Of 301 patients, their average utility score was 0.86±0.17 (range: 0.03-1.00), and the average EQ-visual analogue scale (VAS) score was 69.12±12.60 (range: 30-100). These figures were 0.79±0.21 and 65.20±13.20 for 102 metastatic breast cancer patients, significantly lower than those of 199 non-metastatic cancer patients (0.89±0.13 and 71.13±11.78) (p<0.001), respectively. Lower health-state utility scores were significantly associated with older age (p = 0.002), lower education level (p = 0.006), lower monthly income (p = 0.036), metastatic cancer (p = 0.001), lower EQ-VAS score (p<0.001), and more severe level of distress (p<0.001). CONCLUSIONS: Our findings showed a significant decrement in utility scores among metastatic breast cancer patients. Patients' health-state utility differed by their demographic characteristics (age, education level, and income) and clinical characteristics (stage of cancer and distress). Their utility scores may support further cost-effectiveness analysis in Vietnam.

Application of short tandem repeats (STRs) in the preimplantation genetic diagnosis (PGD) of α-thalassemia.

OBJECTIVES: α-thalassemia is an autosomal recessive monogenic blood disorder, affecting up to 5% of the world's population. The occurrence rate of the disease in Vietnam varies up to up to 51.5%, with high rate of mutation carriers, of couples consisting of two carriers at risk of bearing a child with fetal Hb Bart, which can develop into hydrops fetalis syndrome, threatening the well-being of the mother and the child. Our study aims to facilitate birth of healthy/asymptomatic children of α-thalassemia carrier couples who received reproductive service at our centre during the period of 2019-2022. MATERIALS AND METHODS: 89 couples at risks of having α-thalassemia offsprings requested IVF procedures and PGD at Post Hospital during 2019-2022 were recruited for investigation. Couple and additional family members' peripheral blood samples of couples and additional family members were subjected to haemoglobin electrophoresis, DNA extraction for α-thalassemia gene mutation detection and STRs linkage analysis. Data were observed and analysed on GeneMarker software. RESULTS: 91 cycles of PGD for α-thalassemia were carried out for 89 couples. α-thalassemia large deletion (--SEA/αα) was the most common mutation identified in 88 couples, in which 4 cases also carried ß-thalassemia point mutations. Combining results of PGS and PGD, 278/424 amplified embryos were transferable (HBA-mutation free or carriers of single heterozygous HBA mutation, without chromosomal abnormality). 64/89 couples have been transferred with the embryos (prioritizing mutation free ones over carriers), resulting in the birth of 36 α-thalassemia disease-free children, 17 ongoing pregnancies, and 11 with miscarriages. CONCLUSION: Successful application of microsatellite-based method in PGD facilitated the birth of 36 healthy children and 17 ongoing pregnancies for 53/64 couples with embryo-transferred. All resulted clinical births displayed confirmation results in line with the PGD results, thus demonstrating the feasibility and credibility of the use of STR markers in PGD.

A novel IGHMBP2 variant and clinical diversity in Vietnamese SMARD1 and CMT2S patients.

Background: Pathogenic variants in the IGHMBP2 gene are associated with two distinct autosomal recessive neuromuscular disorders: spinal muscular atrophy with respiratory distress type 1 (SMARD1; OMIM #604320) and Charcot-Marie-Tooth type 2S (CMT2S; OMIM #616155). SMARD1 is a severe and fatal condition characterized by infantile-onset respiratory distress, diaphragmatic palsy, and distal muscular weakness, while CMT2S follows a milder clinical course, with slowly progressive distal muscle weakness and sensory loss, without manifestations of respiratory disorder. Methods: Whole-exome sequencing of the IGHMBP2 gene was performed for eight Vietnamese patients with IGHMBP2-related neuromuscular disorders including five patients with SMARD1 and the others with CMT2S. Results: We identified one novel IGHMBP2 variant c.1574T > C (p.Leu525Pro) in a SMARD1 patient. Besides that, two patients shared the same pathogenic variants (c.1235 + 3A > G/c.1334A > C) but presented completely different clinical courses: one with SMARD1 who deceased at 8 months of age, the other with CMT2S was alive at 3 years old without any respiratory distress. Conclusion: This study is the first to report IGHMBP-2-related neuromuscular disorders in Vietnam. A novel IGHMBP2 variant c.1574T > C (p.Leu525Pro) expressing SMARD1 phenotype was detected. The presence of three patients with the same genotype but distinct clinical outcomes suggested the interaction of variants and other factors including relating modified genes in the mechanism of various phenotypes.