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Abstract The highly polygenic nature of human longevity renders pleiotropy an indispensable feature of its genetic architecture. Leveraging the genetic correlation between aging-related traits (ARTs), we aimed to model the additive variance in lifespan as a function of the cumulative liability from pleiotropic segregating variants. We tracked allele frequency changes as a function of viability across different age bins and prioritized 34 variants with an immediate implication on lipid metabolism, body mass index (BMI), and cognitive performance, among other traits, revealed by PheWAS analysis in the UK Biobank. Given the highly complex and non-linear interactions between the genetic determinants of longevity, we reasoned that a composite polygenic score would approximate a substantial portion of the variance in lifespan and developed the integrated longevity genetic scores (iLGSs) for distinguishing exceptional survival. We showed that coefficients derived from our ensemble model could potentially reveal an interesting pattern of genomic pleiotropy specific to lifespan. We assessed the predictive performance of our model for distinguishing the enrichment of exceptional longevity among long-lived individuals in two replication cohorts (the Scripps Wellderly cohort and the Medical Genome Reference Bank (MRGB)) and showed that the median lifespan in the highest decile of our composite prognostic index is up to 4.8 years longer. Finally, using the proteomic correlates of iLGS, we identified protein markers associated with exceptional longevity irrespective of chronological age and prioritized drugs with repurposing potentials for gerotherapeutics. Together, our approach demonstrates a promising framework for polygenic modeling of additive liability conferred by ARTs in defining exceptional longevity and assisting the identification of individuals at a higher risk of mortality for targeted lifestyle modifications earlier in life. Furthermore, the proteomic signature associated with iLGS highlights the functional pathway upstream of the PI3K-Akt that can be effectively targeted to slow down aging and extend lifespan.

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 β-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.

This paper explores whether green mindfulness is the motivation behind green innovation and whether this relationship is moderated by green transformational leadership. The paper also investigates the indirect influence of green mindfulness on environmental performance through the mediating mechanism of green innovation. The above goals are necessary to find solutions that meet environmental goals, especially in emerging countries such as Vietnam. Data was collected from an online survey of 278 managers in manufacturing firms in Vietnam and analyzed using SmartPLS software with the partial least squares structural equation modeling (PLS-SEM). The results showed that green mindfulness directly affects green innovation, which in turn, contributes positively to environmental performance. Green mindfulness also increases environmental performance through the mediating role of green innovation. Moreover, green transformational leadership moderates the effects of green mindfulness on green innovation. These results contribute to the ability to achieve environmental goals in manufacturing firms. The study shows the role of green mindfulness and green transformational leadership in promoting green innovation and environmental performance in manufacturing firms in emerging market contexts.

BackgroundMetabolic brain imaging with 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is a supportive diagnostic and differential diagnostic tool for neurodegenerative dementias. In the clinic, scans are usually visually interpreted. However, computer-aided approaches can improve diagnostic accuracy. We aimed to build two machine learning classifiers, based on two sets of FDG PET-derived features, for differential diagnosis of common dementia syndromes.MethodsWe analyzed FDG PET scans from three dementia cohorts [63 dementia due to Alzheimer’s disease (AD), 79 dementia with Lewy bodies (DLB) and 23 frontotemporal dementia (FTD)], and 41 normal controls (NCs). Patients’ clinical diagnosis at follow-up (25 ± 20 months after scanning) or cerebrospinal fluid biomarkers for Alzheimer’s disease was considered a gold standard. FDG PET scans were first visually evaluated. Scans were pre-processed, and two sets of features extracted: (1) the expressions of previously identified metabolic brain patterns, and (2) the mean uptake value in 95 regions of interest (ROIs). Two multi-class support vector machine (SVM) classifiers were tested and their diagnostic performance assessed and compared to visual reading. Class-specific regional feature importance was assessed with Shapley Additive Explanations.ResultsPattern- and ROI-based classifier achieved higher overall accuracy than expert readers (78% and 80% respectively, vs. 71%). Both SVM classifiers performed similarly to one another and to expert readers in AD (F1 = 0.74, 0.78, and 0.78) and DLB (F1 = 0.81, 0.81, and 0.78). SVM classifiers outperformed expert readers in FTD (F1 = 0.87, 0.83, and 0.63), but not in NC (F1 = 0.71, 0.75, and 0.92). Visualization of the SVM model showed bilateral temporal cortices and cerebellum to be the most important features for AD; occipital cortices, hippocampi and parahippocampi, amygdala, and middle temporal lobes for DLB; bilateral frontal cortices, middle and anterior cingulum for FTD; and bilateral angular gyri, pons, and vermis for NC.ConclusionMulti-class SVM classifiers based on the expression of characteristic metabolic brain patterns or ROI glucose uptake, performed better than experts in the differential diagnosis of common dementias using FDG PET scans. Experts performed better in the recognition of normal scans and a combined approach may yield optimal results in the clinical setting.

Abstract Alzheimer’s disease (AD) is a genetically complex, multifactorial neurodegenerative disease. It affects more than 45 million people worldwide and currently remains untreatable. Although genome-wide association studies (GWAS) have identified many AD-associated common variants, only about 25 genes are currently known to affect the risk of developing AD, despite its highly polygenic nature. Moreover, the risk variants underlying GWAS AD-association signals remain unknown. Here, we describe a deep post-GWAS analysis of AD-associated variants, using an integrated computational framework for predicting both disease genes and their risk variants. We identified 342 putative AD risk genes in 203 risk regions spanning 502 AD-associated common variants. 246 AD risk genes have not been identified as AD risk genes by previous GWAS collected in GWAS catalogs, and 115 of 342 AD risk genes are outside the risk regions, likely under the regulation of transcriptional regulatory elements contained therein. Even more significantly, for 109 AD risk genes, we predicted 150 risk variants, of both coding and regulatory (in promoters or enhancers) types, and 85 (57%) of them are supported by functional annotation. In-depth functional analyses showed that AD risk genes were overrepresented in AD-related pathways or GO terms—e.g., the complement and coagulation cascade and phosphorylation and activation of immune response—and their expression was relatively enriched in microglia, endothelia, and pericytes of the human brain. We found nine AD risk genes—e.g., IL1RAP, PMAIP1, LAMTOR4—as predictors for the prognosis of AD survival and genes such as ARL6IP5 with altered network connectivity between AD patients and normal individuals involved in AD progression. Our findings open new strategies for developing therapeutics targeting AD risk genes or risk variants to influence AD pathogenesis.

The present study contributes to the understanding of the influence of service employees and the tangible components of the service production and delivery system on perceptions of quality improvement efforts in a service organization. A hierarchical multiple regression with interaction analysis was performed on data collected from a convenience sample of 435 respondents in a higher education institution to assess the main effect of service employees and servicescape, as well as their interactive effect, on customers’ perception of the institution’s quality improvement efforts. The results show a significant effect of service employees, servicescape as well as the interaction between service employees and servicescape in their influence on customers’ perception of quality improvement efforts. The results also reveal that the servicescape intervenes as a moderator variable in the relationship between service employees and quality improvement efforts. Service organizations should therefore focus on the crucial role of service employees during the service encounter and recognize the importance of the servicescape, in view of increasing customers’ favourable perceptions towards the service organisation’s capability to provide better quality in order to satisfy their needs. The study has limited generalization given the convenience sample and the great variety of service industries. It would be helpful to realize similar studies in other service settings and to explore the exact nature of the interaction between service employees and servicescape.

β-thalassemia is an autosomal recessive disease with the reduction or absence in the production of β-globin chain in the hemoglobin, which is caused by mutations in the Hemoglobin subunit beta (HBB) gene. In Vietnam, the number of β-thalassemia carriers range from 1.5 to 25.0%, depending on ethnic and geographical areas, which is much higher than WHO's data worldwide (1.5%). Hence, preimplantation genetic diagnosis (PGD) plays a crucial role in reducing the rate of β-thalassemia affected patients/carriers. In this research, we report the feasibility and reliability of conducting PGD in combination with the use of short tandem repeat (STR) markers in facilitating the birth of healthy children. Six STRs, which were reported to closely linked with the HBB gene, were used on 15 couples of β-thalassemia carriers. With 231 embryos, 168 blastocysts were formed (formation rate of 72.73%), and 88 were biopsied and examined with STRs haplotyping and pedigree analysis. Thus, the results were verified by Sanger sequencing, as a definitive diagnosis. Consequently, 11 over 15 couples have achieved pregnancy of healthy or at least asymptomatic offspring. Only three couples failed to detect any signs of pregnancy such as increased Human Chorionic Gonadotropin (HCG) level, foetal sac, or heart; and one couple has not reached embryo transfer as they were proposed to continue with HLA-matching to screen for a potential umbilical cord blood donor sibling. Thus, these results have indicated that the combination of PGD with STRs analysis confirmed by Sanger sequencing has demonstrated to be a well-grounded and practical clinical strategy to improve the detection of β-thalassemia in the pregnancies of couples at-risk before embryo transfer, thus reducing β-thalassemia rate in the population.

The present study contributes to the understanding of the role of two major components of the service production and delivery system in reinforcing the perceived corporate reputation. Specifically, the purpose of this study is to assess the combined effects of service offering and service employees on customers’ perception of corporate reputation. A hierarchical multiple regression with interaction analysis was performed on data collected from customers of a banking institution to assess the main effect of service offering and service employees, as well as their interactive effect on customers’ perception of corporate reputation. A significant interaction between service offering and service employees in their influence on corporate reputation was found. This results suggest that service employees intervene as a moderator variable in the relationship between service offering and corporate reputation. Furthermore, service organizations should focus on the crucial role of the service offering during the service encounter and recognize the importance of service employees in such way to reinforce customers’ perception of corporate reputation. The study has limited generalization given the convenience sample and the great variety of service industries. The efficacy of the direct measures and the hierarchical multiple regression must be considered. It would be helpful to realize similar studies in other service settings and to explore the exact nature of the interaction between service offering and service employees

As location-based services have become popular, thereby exposed user locations raised serious privacy concerns. A typical measure for location privacy is to report blurred locations and ensure that other users coexist in the reported region. However, additional knowledge about the user's maximum speed and the territorial information in user's vicinity can allow for the adversary to effectively compromise the user's location privacy. In this paper, we present an anonymization algorithm that effectively counters such attacks while achieving k -anonymity requirements as well as minimum acceptable cloaked region size. We evaluate our anonymization scheme using state-of-the-art simulators for both vehicular movements and pedestrian movements. The experimental results demonstrate the effectiveness and efficiency of our proposed algorithm.

A well-established cascade of transcription factor (TF) activity orchestrates adipogenesis in response to chemical cues, yet how cell-intrinsic determinants of differentiation such as cell shape and/or seeding density inform this transcriptional program remain enigmatic. Here, we uncover a novel mechanism licensing transcription in human mesenchymal stem cells (hMSCs) adipogenically primed by confluence. Prior to adipogenesis, confluency promotes heterodimer recruitment of the bZip TFs C/EBPβ and ATF4 to a non-canonical C/EBP DNA sequence. ATF4 depletion decreases both cell-density-dependent transcription and adipocyte differentiation. Global profiling in hMSCs and a novel cell-free assay reveals that ATF4 requires C/EBPβ for genomic binding at a motif distinct from that bound by the C/EBPβ homodimer. Our observations demonstrate that C/EBPβ bridges the transcriptional programs in naïve, confluent cells and early differentiating pre-adipocytes. Moreover, they suggest that homo- and heterodimer formation poise C/EBPβ to execute diverse and stage-specific transcriptional programs by exploiting an expanded motif repertoire.

AimTo assess (1) the overlap rate of gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) and (2) the yield of esophagogastroduodenoscopy in patients clinically presenting with FD.Materials and MethodsOutpatients aged ≥18 years with typical reflux symptoms ≥2 times a week or clinically fulfilling the Rome IV criteria for FD were recruited and underwent esophagogastroduodenoscopy. GERD was classified into non-erosive reflux disease (NERD) and erosive reflux disease (ERD), and FD was classified into epigastric pain syndrome and postprandial distress syndrome. The endoscopic findings that could explain patients’ symptoms were considered clinically significant endoscopic findings. After esophagogastroduodenoscopy, patients were categorized into three groups: GERD-only, FD-only, and GERD-FD overlap.ResultsThere were 439 patients with a mean age of 42.3 ± 11.6 years. Ninety-one (20.7%) patients had clinically significant endoscopic findings: 73 (16.6%) reflux esophagitis, 6 (1.4%) Barrett’s esophagus and 14 (3.2%) gastroduodenal ulcers. After excluding gastroduodenal ulcers, the numbers of patients with GERD-only, FD-only, and GERD-FD overlap were 69 (16.2%), 138 (32.5%), and 218 (51.3%), respectively. Postprandial distress syndrome was more prevalent in GERD-FD overlap than in FD-only (72.9 vs. 44.2%, p < 0.001). The rates of gastroduodenal ulcers in patients clinically fulfilling the criteria for FD with and without reflux symptoms were 0.6 and 4.7%, respectively (p = 0.027).ConclusionThe GERD-FD overlap was more common than each disorder alone, of which postprandial distress syndrome was significantly prominent. Organic dyspepsia was uncommon in patients clinically fulfilling the Rome IV criteria for FD.

The research aimed to explore the antioxidant potential of extracts from different parts of Clinacanthus nutans growing in Vietnam, a member of the Acanthaceae family. The plant's roots, stem, and leaves were extracted using 96% ethanol. The antioxidant actions of these extracts were evaluated by DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay on thin-layer plates and 96 well plates. The extract with the most potent activity was applied for distribution extraction with solvents with different polarities, including dichloromethane, ethyl acetate and water. Dry column vacuum chromatography was utilized to obtain the most antioxidant-potent extract fractions. The stem extract had the lowest IC50 value of 6.85µg/mL, showing the most potent antioxidant activity. The ethyl acetate fraction from the stem extract expressed the lowest IC50 value of 9.67µg/mL. Meanwhile, fraction 5, separated from the ethyl acetate fraction of the stem extract, had the lowest IC50 value of 9.89µg/mL. In conclusion, the extracts from different parts of Clinacanthus nutans all expressed antioxidant action at different levels, in which the stem extract, the ethyl acetate fraction and fraction 5 from the ethyl acetate fraction displayed the most effective actions. These findings highlight the promising potential of Clinacanthus nutans in treating oxidative stress-associated diseases, inspiring further research and exploration in this area. [ABSTRACT FROM AUTHOR]

The pellet supply chain (PSC) is arguably crucial in supplanting fossil energy sources. Despite being the world's second-largest exporter of biomass pellets, the operation of PSC components in Vietnam is still fragmented and lacks economic and environmental efficiency. Changes in Bill of Material (BOM) help achieve these objectives. Discrete event simulation (DES) is particularly adapted to assist business owners in identifying BOM variation and its impacts on their real-life PSCs. Exploiting the advantages of the DES approach, this paper presents an evaluation model for the PSC, including procurement, production, transportation, and delivery modules. Simulation results yield a profit of USD 15,426,661, equivalent to roughly 20% of the revenue. The total amounts of carbon dioxide (CO2) emitted during production and transportation are 7,680.6 and 28,627.0 tons, respectively. The model is further used to assess the volatility of financial indicators and CO2 emission from changes in the raw materials for production. The findings suggest that maintaining the small-scale BOM level should be a solution for improving the economic and environmental efficiency of PSC components in Vietnam. [ABSTRACT FROM AUTHOR]