Design and generation of mRNAs encoding conserved regions of SARS-CoV-2 ORF1ab for T cell-mediated immune activation.

Aim: To generate mRNAs encoding conserved regions within SARS-CoV-2 ORF1ab which can induce strong T-cell responses to overcome the immune invasion of newly emergent variants. Methods: We selected two conserved regions with a high density of T-cell epitopes using immunoinformatics for mRNA synthesis. The ability of testing mRNAs to activate T cells for IFN-γ production was examined by an ELISpot assay and flow cytometry. Results: Two synthesized mRNAs were successfully translated in MDA-MB-231 cells and had comparable potency to the spike mRNA to induce CD4+ and CD8+ T-cell responses in peripheral blood mononuclear cells in 29 out of 34 participants. Conclusion: This study provides a proof-of-concept for the use of SARS-CoV-2 conserved regions to develop booster vaccines capable of eliciting T-cell-mediated immunity.

The interplay between internal communication, employee engagement, job satisfaction, and employee loyalty in higher education institutions in Vietnam.

The present study examines the roles of internal communication (IC), job engagement (JE), organisation engagement (OE) and job satisfaction (JS) in producing employee loyalty (EL) based on the social exchange theory. This study employed an online questionnaire-based survey design to collect data from 255 respondents from higher education institutions (HEIs) in Binh Duong province using convenience and snowball sampling techniques. Data analyses and hypothesis testing were carried out using the partial least squares structural equation modelling (PLS-SEM). The findings show that all relationships are significantly validated, except for the JE-JS relationship. Our work is the first to investigate employee loyalty in the HEI context of an emerging economy such as Vietnam by incorporating internal communication, employee engagement (including job and organisation engagement) and job satisfaction to develop and validate a research model for the study. This study is expected to contribute to the theory and advance our understanding of different mechanisms that job engagement, organisation engagement and job satisfaction can play in the relationship between internal communication and employee loyalty.

Fragment length profiles of cancer mutations enhance detection of circulating tumor DNA in patients with early-stage hepatocellular carcinoma.

BACKGROUND: Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity. METHODS: Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC. RESULTS: Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%. CONCLUSIONS: Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.

Ultra-Deep Sequencing of Plasma-Circulating DNA for the Detection of Tumor- Derived Mutations in Patients with Nonmetastatic Colorectal Cancer.

Identification of tumor-derived mutation (TDM) in liquid biopsies (LB), especially in early-stage patients, faces several challenges, including low variant-allele frequencies, interference by white blood cell (WBC)-derived mutations (WDM), benign somatic mutations and tumor heterogeneity. Here, we addressed the above-mentioned challenges in a cohort of 50 nonmetastatic colorectal cancer patients, via a workflow involving parallel sequencing of paired WBC- and tumor-gDNA. After excluding potential false positive mutations, we detected at least one TDM in LB of 56% (28/50) of patients, with the majority showing low-patient coverage, except for one TDM mapped to KMT2D that recurred in 30% (15/30) of patients.

Analgesic effect of non-nutritive sucking in term neonates: A randomized controlled trial.

BACKGROUND: Newborns commonly experience pain due to a variety of reasons. Non-nutritive sucking (NNS) is thought to be an effective non-pharmacological method of pain-relief. However, the significant heterogeneity in some systematic reviews limited the certainty of the findings about NNS. Hence, this study was aimed at evaluating the analgesic effect and safety of NNS in healthy term neonates during the heel prick test, using the Neonatal Pain Agitation and Sedation Scale (N-PASS). METHODS: In this randomized controlled trial, 42 term infants were included: 22 infants in the intervention group (receiving NNS) and 20 infants in the control group (not receiving NNS). In the intervention group, neonates were given a silicone pacifier 120 s before, during, and 120 s after the heel puncture, while neonates in the control group received routine care. Pain-related outcomes were assessed using the N-PASS at 30s, 60s, 90s, and 120s after the heel prick. Any adverse events during the procedure were noted. The Spearman correlation coefficients between the pain scores on the N-PASS and two other scales (NFCS and NIPS) were calculated at all four moments of evaluation. RESULTS: The mean N-PASS pain scores at 30s, 60s, 90s, and 120s after heel prick were significantly lower in the NNS group than in the control group: 4.73 ± 2.78 vs. 7.90 ± 1.52 (p = 0.0002); 3.64 ± 3.06 vs. 5.55 ± 2.95 (p = 0.052); 2.59 ± 3.08 vs. 5.25 ± 3.51 (p = 0.011); and 2.05 ± 2.94 vs. 4.90 ± 3.99 (p = 0.013), respectively. No adverse events were detected in either group. Our findings revealed a strong positive correlation between the pain scores on the N-PASS and two other scales (NFCS and NIPS), which was statistically significant (p < 0.01). CONCLUSIONS: NNS is considered a safe and effective pain-relief method during the heel prick procedure in term neonates, demonstrated using the N-PASS. These findings were correlated with the pain evaluation by NFCS and NIPS.

Vietnam as a case example of school-based mental health services in low and middle income countries: Efficacy and effects of risk status.

The purposes of this study were to (a) assess the efficacy of a universal classroom-based mental health and social skills program for primary school students in Vietnam, and (b) given the universal nature of the intervention, assess outcomes as a function of risk status (high vs. low). RECAP-VN is a semi-structured program that provides students with classroom social skills training, and teachers with in-classroom consultation on program implementation and classroom-wide behavior management. Project data were collected at three time-points across the academic year from 443 2nd grade students in regards to their social skills and mental health functioning, in the Vietnamese cities of Hanoi and Danang. Mental health functioning (emotional and behavioral mental health problems) was the ultimate outcome target (at Time 3), with social skills intermediate (at Time 2) outcomes targeted to improve mental health functioning. Significant treatment effects were found on both social skills and mental health functioning. However, although program effects on mental health functioning were significant for both low and high risk status groups, program effects on social skills were only significant for low risk status students, suggesting that different mechanisms may underlie program effects for high and low risk status students. Overall the results of this study, one of the first to assess directly the effects of a school-based program on mental health functioning in a low or middle income country, provide some support for the value of using school-based programs to address the substantial child mental health treatment gap found in low- and middle-income countries.