FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy.

Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B cell lymphoma and multiple myeloma1-4, but the efficacy of CAR T cell therapy in solid tumours has been limited5. This is owing to a number of factors, including the immunosuppressive tumour microenvironment that gives rise to poorly persisting and metabolically dysfunctional T cells. Analysis of anti-CD19 CAR T cells used clinically has shown that positive treatment outcomes are associated with a more 'stem-like' phenotype and increased mitochondrial mass6-8. We therefore sought to identify transcription factors that could enhance CAR T cell fitness and efficacy against solid tumours. Here we show that overexpression of FOXO1 promotes a stem-like phenotype in CAR T cells derived from either healthy human donors or patients, which correlates with improved mitochondrial fitness, persistence and therapeutic efficacy in vivo. This work thus reveals an engineering approach to genetically enforce a favourable metabolic phenotype that has high translational potential to improve the efficacy of CAR T cells against solid tumours.

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) arrays are 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. SNP arrays designed for these countries should be cost-effective (small size), yet incorporate 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 not included in the array (imputed SNPs) can be predicted. However, current tag SNP selection methods mostly focus on imputation accuracy and coverage, but not the functional content of the array. It is those functional SNPs that are most likely associated with 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 show 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. $\textrm{LmTag}$ is available at: https://github.com/datngu/LmTag.

Assessing polygenic risk score models for applications in populations with under-represented genomics data: an example of Vietnam.

Most polygenic risk score (PRS)models have been based on data from populations of European origins (accounting for the majority of the large genomics datasets, e.g. >78% in the UK Biobank and >85% in the GTEx project). Although several large-scale Asian biobanks were initiated (e.g. Japanese, Korean, Han Chinese biobanks), most other Asian countries have little or near-zero genomics data. To implement PRS models for under-represented populations, we explored transfer learning approaches, assuming that information from existing large datasets can compensate for the small sample size that can be feasibly obtained in developing countries, like Vietnam. Here, we benchmark 13 common PRS methods in meta-population strategy (combining individual genotype data from multiple populations) and multi-population strategy (combining summary statistics from multiple populations). Our results highlight the complementarity of different populations and the choice of methods should depend on the target population. Based on these results, we discussed a set of guidelines to help users select the best method for their datasets. We developed a robust and comprehensive software to allow for benchmarking comparisons between methods and proposed a computational framework for improving PRS performance in a dataset with a small sample size. This work is expected to inform the development of genomics applications in under-represented populations. PRSUP framework is available at: https://github.com/BiomedicalMachineLearning/VGP.

An integrative pipeline for circular RNA quantitative trait locus discovery with application in human T cells.

MOTIVATION: Molecular quantitative trait locus (QTL) mapping has proven to be a powerful approach for prioritizing genetic regulatory variants and causal genes identified by genome-wide association studies. Recently, this success has been extended to circular RNA (circRNA), a potential group of RNAs that can serve as markers for the diagnosis, prognosis, or therapeutic targets of various human diseases. However, a well-developed computational pipeline for circRNA QTL (circQTL) discovery is still lacking. RESULTS: We introduce an integrative method for circQTL mapping and implement it as an automated pipeline based on Nextflow, named cscQTL. The proposed method has two main advantages. Firstly, cscQTL improves the specificity by systematically combining outputs of multiple circRNA calling algorithms to obtain highly confident circRNA annotations. Secondly, cscQTL improves the sensitivity by accurately quantifying circRNA expression with the help of pseudo references. Compared to the single method approach, cscQTL effectively identifies circQTLs with an increase of 20%-100% circQTLs detected and recovered all circQTLs that are highly supported by the single method approach. We apply cscQTL to a dataset of human T cells and discover genetic variants that control the expression of 55 circRNAs. By colocalization tests, we further identify circBACH2 and circYY1AP1 as potential candidates for immune disease regulation. AVAILABILITY AND IMPLEMENTATION: cscQTL is freely available at: https://github.com/datngu/cscQTL and https://doi.org/10.5281/zenodo.7851982.

Enforcing Metal-Arene Interactions in Bulky p-Terphenyl Bis(anilide) Complexes of Group 2 Metals (Be-Ba): Potential Precursors for Low-Oxidation-State Alkaline Earth Metal Systems.

An extremely bulky p-terphenyl bis(aniline), p-C6H4{C6H4[N(H)TCHP]-2}2 (TCHP = 2,4,6-tricyclohexylphenyl) TCHPTerphH2, has been developed. Deprotonation of a less bulky analogue, DipTerphH2 (Dip = 2,6-diisopropylphenyl), with BePh2 affords the bimetallic system, [(BePh)2(µ-DipTerph)] 1. Treating either TCHPTerphH2 or DipTerphH2 with Mg{CH2(SiMe3)}2 gives the monomeric bis(anilide) complexes [Mg(ArTerph)] (Ar = Dip 2, TCHP 3) which display rare examples of η6-arene coordination to the metal center. Treating 2 with THF leads to partial dissociation of the Mg···arene interaction and formation of [Mg(DipTerph)(THF)] 4. Reactions of the bis(aniline)s with the group 2 metal amides [M{N(SiMe3)2}2] afford dimeric, structurally analogous compounds [{M(ArTerph)}2] (Ar = Dip, M = Ca 5, Sr 6, Ba 7; Ar = TCHP, M = Ca 8, Sr 9, Ba 10) which display intermolecular M···arene interactions in the solid state. Computational studies have shown that the intramolecular M···Î·6-arene interactions in models of the ether-free metal bis(anilide) compounds are largely electrostatic in nature. Reductions of these compounds with alkali metals led to mixtures of unidentified products.

Mfsd7b facilitates choline transport and missense mutations affect choline transport function.

MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.

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.

A Comprehensive Evaluation of Dioxins and Furans Occurrence in River Sediments from a Secondary Steel Recycling Craft Village in Northern Vietnam.

This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.

Expanded vaccination practice in 2-year-old children and maternal knowledge on expanded vaccination in Tien Giang, Vietnam.

Background: Vaccination plays a central role in protecting children against severe diseases and preventing child mortality. Objectives: This study aimed to determine the rate and factors associated with complete and timely vaccination in 2-year-old children, as well as maternal knowledge on expanded vaccination in Go Cong Tay district, Tien Giang province, Vietnam. Methods: A cross-sectional descriptive study was conducted on 558 2-year-old children and their mothers residing in Go Cong Tay district, Tien Giang province, Vietnam. The study employed a systematic random sampling method from June to September 2021. Results: The rate of complete vaccination in children was 74.7%. Factors associated with the rate of complete vaccination were occupation (OR=0.3; 95%CI: 0.1-0.7; p=0.006), economic status (OR=3.8; 95%CI: 1.7-8.6; p=0.001), and maternal general knowledge on expanded vaccination (OR=1.7; 95%CI: 1.1-2.6; p=0.01). The rate of timely vaccination was 47.8%. Factors associated with the rate of timely vaccination were maternal age group (OR=3.1; 95%CI: 1.6-6.0; p=0.001; OR=3.0; 95%CI: 1.3-6.6; p=0.006) and economic status (OR=0.4; 95%CI: 0.2-0.9; p=0.04). The rate of both complete and timely vaccination was 22.6%. Factors associated with the rate of complete and timely vaccination were maternal age group (OR=3.1; 95%CI: 1.3-7.2; p=0.009; OR=3.3; 95%CI: 1.2-9.1; p=0.02) and maternal general knowledge on expanded vaccination (OR=1.5; 95%CI: 1.0-2.4; p=0.03). The rate of maternal general knowledge on expanded vaccination was 57.5%. Conclusion: The rates of complete and timely vaccination are still low, and various factors influence expanded vaccination. The-refore, it is crucial to continue health education campaigns to improve knowledge on expanded vaccination, remind mothers of vaccination schedules, strengthen confidence in vaccination programs and vaccine safety, attract customers to vaccination services, provide adequate healthcare for children, and ensure vaccination activities during disease outbreaks.

Prevalence of stress and related factors among healthcare students: a cross - sectional study in Can Tho City, Vietnam.

Background: Stress is a major public health issue that can impact both physical and mental well-being. It is prevalent in many areas of modern life, including education. Healthcare students are at a high risk of experiencing stress due to the unique demands of their fields of study. Study design and methods: An online survey was conducted on 2,515 undergraduate students pursuing degrees in medicine, preventive medicine, pharmacy, and nursing at Can Tho University of Medicine and Pharmacy in Can Tho City, Vietnam. Results: Using the Perceived Stress Scale-10 (PSS-10), it was found that 35.2% of students reported mild stress, 62.7% had moderate stress, and only 2.1% experienced severe stress. Multivariable logistic regression analysis revealed nine significant factors associated with students' stress levels (p ≤ 0.05). Particularly, medicine students exhibited a significantly higher level of moderate and severe stress (95% CI = 1.22-2.01), 1.57 times higher than preventive medicine students. Sixth-year students had a stress level 1.58 times higher (95% CI = 1.11-2.26) than first-year students. Students achieving excellent and very good academic performances in the last semester had a stress level 1.60 times higher (95% CI = 1.16-2.22) than students with average and lower academic performance. Students living at home had a stress level 1.73 times higher (95% CI = 1.05-2.84) than students living in their relatives' houses. Students who rarely or never had a part-time job during academic years had a stress level 1.70 times higher (95% CI = 1.31-2.20) than those who often or sometimes had a part-time job. Students with a family history of smoking addiction had a stress level 1.69 times higher (95% CI = 1.28-2.22) than students without such a family history. Students who rarely or never received concern and sharing from family had a stress level 7.41 times higher (95% CI = 5.07-10.84) than students who often or sometimes received concern and sharing from family. Students who were often or sometimes cursed by family had a stress level 2.04 times higher (95% CI = 1.09-3.81) than students who were rarely or never cursed by family. Students without close friends had a stress level 1.46 times higher (95% CI = 1.11-1.91) than students with close friends. Conclusions: The rates of mild and moderate stress levels were significantly higher than severe stress level among healthcare students. Research has provided scientific findings as the basis for determining risk factors and imposing solutions that aim to reduce the rate of stress in students. Therefore, it helps students overcome difficulties and enhance their physical and mental health.

Variations in Intracellular Organometallic Reaction Frequency Captured by Single-Molecule Fluorescence Microscopy.

Studies of organometallic reactions in living cells commonly rely on ensemble-averaged measurements, which can obscure the detection of reaction dynamics or location-specific behavior. This information is necessary to guide the design of bioorthogonal catalysts with improved biocompatibility, activity, and selectivity. By leveraging the high spatial and temporal resolution of single-molecule fluorescence microscopy, we have successfully captured single-molecule events promoted by Ru complexes inside live A549 human lung cells. By observing individual allylcarbamate cleavage reactions in real-time, our results revealed that they occur with greater frequency inside the mitochondria than in the non-mitochondria regions. The estimated turnover frequency of the Ru complexes was at least 3-fold higher in the former than the latter. These results suggest that organelle specificity is a critical factor to consider in intracellular catalyst design, such as in developing metallodrugs for therapeutic applications.

Biodegradable and Inherently Fluorescent pH-Responsive Nanoparticles for Cancer Drug Delivery.

PURPOSE: The development of two novel pH-only and pH- and thermo-responsive theranostic nanoparticle (NP) formulations to deliver an anticancer drug and track the accumulation and therapeutic efficacy of the formulations through inherent fluorescence. METHODS: A pH-responsive formulation was synthesized from biodegradable photoluminescent polymer (BPLP) and sodium bicarbonate (SBC) via an emulsion technique, while a thermoresponsive BPLP copolymer (TFP) and SBC were used to synthesize a dual-stimuli responsive formulation via free radical co-polymerization. Cisplatin was employed as a model drug and encapsulated during synthesis. Size, surface charge, morphology, pH-dependent fluorescence, lower critical solution temperature (LCST; TFP NPs only), cytocompatibility and in vitro uptake, drug release kinetics and anticancer efficacy were assessed. RESULTS: While all BPLP-SBC and TFP-SBC combinations produced spherical nanoparticles of a size between 200-300 nm, optimal polymer-SBC ratios were selected for further study. Of these, the optimal BPLP-SBC formulation was found to be cytocompatible against primary Type-1 alveolar epithelial cells (AT1) up to 100 µg/mL, and demonstrated sustained drug release over 14 days, dose-dependent uptake, and marked pH-dependent A549 cancer cell killing (72 vs. 24% cell viability, at pH 7.4 vs. 6.0). The optimal TFP-SBC formulation showed excellent cytocompatibility against AT1 cells up to 500 µg/mL, sustained release characteristics, dose-dependent uptake, pH-dependent (78% at pH 7.4 vs. 64% at pH 6.0 at 37°C) and marked temperature-dependent A549 cancer cell killing (64% at 37°C vs. 37% viability at pH 6.0, 41°C). CONCLUSIONS: In all, both formulations hold promise as inherently fluorescent, stimuli-responsive theranostic platforms for passively targeted anti-cancer therapy.

Stent-Graft Treatment of a Giant Asymptomatic Extracranial Vertebral Artery Aneurysm: Case Report and Literature Review.

With the widespread appliance of endovascular techniques, a plethora of options is available in the treatment of extracranial vertebral artery aneurysms. If the vertebral artery can be sacrificed, embolization with coiling, liquid injection, or parent artery exclusion can be done. We hereby present a case of a 74-year-old male patient presenting with an asymptomatic atherosclerotic giant extracranial vertebral artery aneurysm in the V1 segment of the vertebral artery, successfully treated with balloon expandable stent-graft deployment. No neurologic symptoms occurred, and the stent-graft was patent with no signs of endoleak at 24 months follow-up with computed tomography angiography.

Genetic analysis of Vietnamese patients with early-onset Alzheimer's disease.

Purpose of the study: Alzheimer's disease (AD) is the most common type of dementia and its prevalence is rapidly increasing worldwide. Early-onset Alzheimer's disease (EOAD) constitutes of patients with age of onset earlier than 65 year-old and is known to be associated with genetic mutations. In this study, we reported the first genetic analysis of Vietnamese patients with EOAD.Materials and methods: We analyzed targeted sequencing data obtained from a cohort of 51 Vietnamese EOAD patients to identify pathogenic variants in twenty nine well-characterized neurodengerative genes.Results: We identified four missense mutations in APP/PSEN1 genes from six individuals, which accounts for 11.8% of all tested cases. Three of these mutations were previously reported as pathogenic and one mutation in the APP gene was newly identified and might be specific for Vietnamese patients. Our study also found eight individuals carrying homozygous APOE ε4 allele, the main risk factor gene for late-onset AD.Conclusions: Our findings showed that mutation rate in APP/PSEN genes in Vietnamese EOAD patients is consistent with that in other ethnic groups. Although further functional studies are required to validate the pathogenesis of the new mutations, our study demonstrated the necessity of genetic screening for EOAD patients as well as additional genetic data collection in Vietnamese population.

End-to-end artificial intelligence platform for the management of large vessel occlusions: A preliminary study.

OBJECTIVES: In this study, we developed a deep learning pipeline that detects large vessel occlusion (LVO) and predicts functional outcome based on computed tomography angiography (CTA) images to improve the management of the LVO patients. METHODS: A series identifier picked out 8650 LVO-protocoled studies from 2015 to 2019 at Rhode Island Hospital with an identified thin axial series that served as the data pool. Data were annotated into 2 classes: 1021 LVOs and 7629 normal. The Inception-V1 I3D architecture was applied for LVO detection. For outcome prediction, 323 patients undergoing thrombectomy were selected. A 3D convolution neural network (CNN) was used for outcome prediction (30-day mRS) with CTA volumes and embedded pre-treatment variables as inputs. RESULT: For LVO-detection model, CTAs from 8,650 patients (median age 68 years, interquartile range (IQR): 58-81; 3934 females) were analyzed. The cross-validated AUC for LVO vs. not was 0.74 (95% CI: 0.72-0.75). For the mRS classification model, CTAs from 323 patients (median age 75 years, IQR: 63-84; 164 females) were analyzed. The algorithm achieved a test AUC of 0.82 (95% CI: 0.79-0.84), sensitivity of 89%, and specificity 66%. The two models were then integrated with hospital infrastructure where CTA was collected in real-time and processed by the model. If LVO was detected, interventionists were notified and provided with predicted clinical outcome information. CONCLUSION: 3D CNNs based on CTA were effective in selecting LVO and predicting LVO mechanical thrombectomy short-term prognosis. End-to-end AI platform allows users to receive immediate prognosis prediction and facilitates clinical workflow.

Polybrominated diphenyl ethers in indoor dusts from industrial factories, offices, and houses in northern Vietnam: Contamination characteristics and human exposure.

Information about the occurrence of polybrominated diphenyl ethers (PBDEs) in indoor dusts from various industrial sectors in Southeast Asia is still scarce. In this study, concentrations and congener-specific profiles of PBDEs were determined in indoor dusts from industrial factories, offices, and houses in northern Vietnam. Levels of Σ8PBDEs were higher in the office dusts (median 270; range 230-300 ng/g) and factory dusts (170; 89-510 ng/g) than in the house dusts (61; 25-140 ng/g). BDE-209 was the most dominant congener, accounting for 27-98% (average 62%) of Σ8PBDEs, suggesting the abundance of products treated with deca-BDE mixtures. Residential, commercial, and industrial activities in the studied locations of this survey were not significant sources of PBDEs as compared to those of informal waste processing activities in Vietnam. Relatively low PBDE concentrations detected in our dust samples partially reflect effectiveness of the global PBDE phase-out. Human exposure and health risk associated with dust-bound PBDEs were estimated, indicating acceptable levels of risk (i.e., neurobehavioral effects). The contributions of workplace dusts in total daily intake doses of PBDEs via dust ingestion were more important for local workers in informal recycling areas than factory workers and general population, raising the need of appropriate labor protection measures.

Circall: fast and accurate methodology for discovery of circular RNAs from paired-end RNA-sequencing data.

BACKGROUND: Circular RNA (circRNA) is an emerging class of RNA molecules attracting researchers due to its potential for serving as markers for diagnosis, prognosis, or therapeutic targets of cancer, cardiovascular, and autoimmune diseases. Current methods for detection of circRNA from RNA sequencing (RNA-seq) focus mostly on improving mapping quality of reads supporting the back-splicing junction (BSJ) of a circRNA to eliminate false positives (FPs). We show that mapping information alone often cannot predict if a BSJ-supporting read is derived from a true circRNA or not, thus increasing the rate of FP circRNAs. RESULTS: We have developed Circall, a novel circRNA detection method from RNA-seq. Circall controls the FPs using a robust multidimensional local false discovery rate method based on the length and expression of circRNAs. It is computationally highly efficient by using a quasi-mapping algorithm for fast and accurate RNA read alignments. We applied Circall on two simulated datasets and three experimental datasets of human cell-lines. The results show that Circall achieves high sensitivity and precision in the simulated data. In the experimental datasets it performs well against current leading methods. Circall is also substantially faster than the other methods, particularly for large datasets. CONCLUSIONS: With those better performances in the detection of circRNAs and in computational time, Circall facilitates the analyses of circRNAs in large numbers of samples. Circall is implemented in C++ and R, and available for use at https://www.meb.ki.se/sites/biostatwiki/circall and https://github.com/datngu/Circall.

Survival after out-of-hospital cardiac arrest, Viet Nam: multicentre prospective cohort study.

OBJECTIVE: To investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam. METHODS: We did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis. FINDINGS: Of 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54-9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03-8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33-12.74). CONCLUSION: Improvements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.

Bempedoic Acid: A New Drug for an Old Problem.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of bempedoic acid for low-density lipoprotein cholesterol (LDL-C) reduction. DATA SOURCES: A PubMed search was conducted from January 2000 to June 15, 2020, using the keyword bempedoic acid for phase III clinical trials published in the English language. STUDY SELECTION AND DATA EXTRACTION: Articles related to the Food and Drug Administration (FDA) approval of bempedoic acid and other trials relating to the safety and efficacy of this drug were included. DATA SYNTHESIS: The findings from this review show that bempedoic acid is a safe and effective option for lowering LDL-C levels in patients requiring LDL-C lowering for primary or secondary prevention of cardiovascular events. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Statin therapy remains the mainstay of treatment for both primary and secondary prevention. However, many patients cannot tolerate statin therapy because of statin-associated muscle symptoms. Bempedoic acid may be a reasonable adjunct for LDL-C reduction, though further evaluation of cardiovascular outcomes with bempedoic acid in this population is needed. CONCLUSIONS: The recent FDA approval of bempedoic acid offers an additional option for lowering LDL-C levels in patients with atherosclerotic cardiovascular disease or heterozygous familial hyperlipidemia. Additional data regarding effect on long-term cardiovascular outcomes with bempedoic acid are currently being studied.

New triterpene sulfates from Vietnamese red alga Tricleocarpa fragilis and their α-glucosidase inhibitory activity.

Three new compounds (methyl-3ß,25-dihydroxycycloart-23-en-29-oate 3-sulfate (1), methyl-3ß-hydroxy-25-methoxycycloart-23-en-29-oate 3-sulfate (2) and 3ß-hydroxy-25-methoxycycloart-23-ene 3-sulfate (3)) and a known one (3ß-hydroxycycloart-24-en-23-one 3-sulfate (4)) were isolated from Vietnamese red alga Tricleocarpa fragilis. All isolated compounds 1-4 showed potent inhibitory activity against yeast α-glucosidase with IC50 values of 16.62 ± 2.80, 36.34 ± 4.04, 30.19 ± 5.01 and 6.52 ± 0.17 µM, respectively. The docking data showed that the substitutions at C-3 and the differences in the side chain of cycloartane-skeleton could influence the interaction of molecule with enzyme, which was consistent with the experimental findings.[Formula: see text].