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.

The OPI•AID Zone Tool as a composite outcome for postoperative pain management quality-A protocol for an observational pilot study.

BACKGROUND: Managing postoperative pain while minimizing opioid-related adverse drug events (ORADEs) remains a significant challenge. The OPI•AID Zone Tool is proposed as a novel clinical decision support tool that - both graphically and in a scoring-system - represents the relationship between pain management and the occurrence of ORADEs, aiming to enhance patient outcomes in postoperative care. The OPI•AID Zone Tool places pain score on the x-axis and an ORADE score on the y-axis, and stratifies patients into five zones to reflect the composite impact of pain severity and ORADEs on the quality of postoperative patient care. The study will have two key aims: (1) to explore whether the OPI•AID Zone Tool can function as a composite outcome measure for postoperative pain and ORADEs, and (2) to evaluate the use of the OPI•AID Zone Tool in visual presentations and for evaluation of patients' postoperative pain management quality. METHODS: This prospective observational cohort study will include 200 adults undergoing various surgical procedures in general anesthesia with a subsequent stay in the post-anesthesia care unit (PACU) at Bispebjerg Hospital, Denmark. Substudy 1 primary outcome: To assess whether a zone score in the OPI•AID Zone Tool is associated with patient-perceived health (EQ VAS), quality of recovery (QoR-PACU), and time to discharge readiness in PACU, and if the zone score has a stronger association than pain and ORADE score in themselves. Substudy 2 primary outcome: To assess how the use of intraoperative non-opioid analgesics impact where patients are placed in the OPI•AID Zone Tool's XY scatterplot right after surgery. To assess if patients who receive more comprehensive non-opioid analgesic basic regimens, generally fall into lower zones. CONCLUSION: The OPI•AID Zone Tool could potentially be a valuable clinical decision-making tool for optimizing postoperative care by simultaneously addressing pain management and the risk of ORADEs. By computing a composite measure of these two critical outcomes, the tool could guide more nuanced and patient-centered analgesic regimens, potentially improving patient satisfaction and operational efficiency in postoperative settings. The tool's applicability will be explored in this observational pilot and followed up in a planned series of studies (opiaid.dk).

Spin-labeling Insights into How Chemical Fixation Impacts Glycan Organization on Cells.

As new methods to interrogate glycan organization on cells develop, it is important to have a molecular level understanding of how chemical fixation can impact results and interpretations. Site-directed spin labeling technologies are well suited to study how the spin label mobility is impacted by local environmental conditions, such as those imposed by cross-linking effects of paraformaldehyde cell fixation methods. Here, we utilize three different azide-containing sugars for metabolic glycan engineering with HeLa cells to incorporate azido glycans that are modified with a DBCO-based nitroxide moiety via click reaction. Continuous wave X-band electron paramagnetic resonance spectroscopy is employed to characterize how the chronological sequence of chemical fixation and spin labeling impacts the local mobility and accessibility of the nitroxide-labeled glycans in the glycocalyx of HeLa cells. Results demonstrate that chemical fixation with paraformaldehyde can alter local glycan mobility and care should be taken in the analysis of data in any study where chemical fixation and cellular labeling occur.

Improving the prediction of wildfire susceptibility on Hawai'i Island, Hawai'i, using explainable hybrid machine learning models.

This study presents a comparative analysis of four Machine Learning (ML) models used to map wildfire susceptibility on Hawai'i Island, Hawai'i. Extreme Gradient Boosting (XGBoost) combined with three meta-heuristic algorithms - Whale Optimization (WOA), Black Widow Optimization (BWO), and Butterfly Optimization (BOA) - were employed to map areas susceptible to wildfire. To generate a wildfire inventory, 1408 wildfire points were identified within the study area from 2004 to 2022. The four ML models (XGBoost, WOA-XGBoost, BWO-XGBoost, and BOA-XGBoost) were run using 14 wildfire-conditioning factors categorized into four main groups: topographical, meteorological, vegetation, and anthropogenic. Six performance metrics - sensitivity, specificity, positive predictive values, negative predictive values, the Area Under the receiver operating characteristic Curve (AUC), and the average precision (AP) of Precision-Recall Curves (PRCs) - were used to compare the predictive performance of the ML models. The SHapley Additive exPlanations (SHAP) framework was also used to interpret the importance values of the 14 influential variables for the modeling of wildfire on Hawai'i Island using the four models. The results of the wildfire modeling indicated that all four models performed well, with the BWO-XGBoost model exhibiting a slightly higher prediction performance (AUC = 0.9269), followed by WOA-XGBoost (AUC = 0.9253), BOA-XGBoost (AUC = 0.9232), and XGBoost (AUC = 0.9164). SHAP analysis revealed that the distance from a road, annual temperature, and elevation were the most influential factors. The wildfire susceptibility maps generated in this study can be used by local authorities for wildfire management and fire suppression activity.

Novel single nucleotide polymorphisms of insulin-like growth factor-binding protein 7 (IGFBP7) gene significantly associated with growth traits in striped catfish (Pangasianodon hypophthalmus Sauvage, 1878).

Breeding program to improve economically important growth traits in striped catfish (Pangasianodon hypophthalmus) requires effective molecular markers. This study was conducted to identify single nucleotide polymorphisms (SNPs) of Insulin-like Growth Factor-Binding Protein 7 (IGFBP7) gene which plays multiple roles in regulating growth, energy metabolism and development. The association between SNPs in IGFBP7 gene and growth traits in striped catfish was analyzed in order to uncover the SNPs that have potential to be valuable markers for improving growth traits. Firstly, fragments of IGFBP7 gene from ten fast-growing fish and ten slow-growing fish were sequenced in order to discover SNPs. After filtering the detected SNPs, an intronic SNP (2060A > G) and two non-synonymous SNPs (344 T > C and 4559C > A) causing Leu78Pro and Leu189Met in protein, respectively, were subjected to further validated by individual genotyping in 70 fast-growing fish and 70 slow-growing fish using single base extension method. Our results showed that two SNPs (2060A > G and 4559 C > A (p. Leu189Met)) were significantly associated with the growth in P. hypophthalmus (p < 0.001), thus being candidate SNP markers for the growth traits of this fish. Moreover, linkage disequilibrium and association analysis with growth traits of haplotypes generated from the 3 filtered SNPs (344 T > C, 2060 A > G and 4559 C > A) were examined. These revealed that the non-coding SNP locus (2060A > G) had higher genetic diversity at which the G allele was predominant over the A allele in the fast-growing fish. Furthermore, the results of qPCR showed that expression of IGFBP7 gene with genotype GG (at locus 2060) in fast-growing group was significantly higher than that with genotype AA in slow-growing group (p < 0.05). Our study provides insights into the genetic variants of IGFBP7 gene and useful data source for development molecular marker for growth traits in breeding of the striped catfish.

Person-specific evidence has the ability to mobilize relational capacity: A four-step grounded theory developed in people with long-term health conditions.

Person-specific evidence was developed as a grounded theory by analyzing 20 selected case descriptions from interventions using the guided self-determination method with people with various long-term health conditions. It explains the mechanisms of mobilizing relational capacity by including person-specific evidence in shared decision-making. Person-specific self-insight was the first step, achieved as individuals completed reflection sheets enabling them to clarify their personal values and identify actions or omissions related to self-management challenges. This step paved the way for sharing these insights and challenges in a relationship with a supportive health professional, who could then rely on person-specific evidence instead of assumptions or a narrow disease perspective for shared decision-making. Trust in the evidence encouraged the supportive health professional to transfer it to the interdisciplinary team. Person-specific evidence then enhanced the ability of team members to apply general evidence in a meaningful way. The increased openness achieved by individuals through these steps enabled them to eventually share their new self-insights in daily life with other people, decreasing loneliness they experienced in self-management. Relational capacity, the core of the theory, is mobilized in both people with long-term health conditions and healthcare professionals. Further research on person-specific evidence and relational capacity in healthcare is recommended.

Effects of core buildup composite resin translucency on intraoral scanner accuracy: an in vitro study.

AIM: The accuracy of 3D images produced by an intraoral scanner (IOS) is affected by the optical characteristics of restorative materials such as metal, ceramic, and composite resin. The present in vitro study aimed to investigate the impact of core buildup composite resin translucency on IOS accuracy. MATERIALS AND METHODS: A core buildup procedure was performed on a proprietary 3D-printed model using injectable composite resins in four groups with different levels of translucency (highest to lowest: AE, A3, AO3, and EX). Ten experimental scans per group were performed using a Medit i700 IOS on a phantom head-mounted model. Reference scans were obtained using an industrial scanner (Solutionix C500). Values of accuracy (trueness and precision) for the respective groups were evaluated using mean deviation values following 3D superimposition. RESULTS: Composite resin translucency caused the scale reduction of the optical impressions. Values of trueness showed the highest scale reduction in AE, significantly, followed by A3, AO3, and EX. Considering 50 µm as the cut-off value of deviations for clinical acceptability, the analysis showed most deviations in AE and A3. Similar results were found with precision, where AE showed the highest deviation value statistically, followed by A3, AO3, and EX. CONCLUSIONS: Composite resin translucency affects the accuracy of optical impressions, causing a fitting error of CAD/CAM prostheses. The more translucent the composite resin, the less accurate the optical impression. This suggests the need for proper compensation during prosthesis designing for an optimal clinical result. In addition, practitioners should indicate in the digital workflow the proper restorative materials regarding not only the mechanical properties and esthetics, but also the optical characteristics.

The role of capital structure management in maintaining the financial stability of hotel firms during the pandemic-A global investigation.

Due to the detrimental effects of the Covid-19 pandemic on the hotel sector, pandemic crisis management research has received lots of academic attention, from studies in sales-marketing to human resource management. However, financial management has been largely overlooked in the agenda of pandemic crisis management and hotel resilience. Therefore, this paper aims to address the research gap by exploring the role of capital structure management in maintaining financial stability and resilience capacities of hotel firms during this evolving and unpredictable Covid-19 pandemic. Using a database of 1882 firm-quarter observations of 196 hotel firms in 30 countries from Quarter 3 2018 to Quarter 2 2021, it is found that low debt capital structure mitigates the adverse impact of the pandemic on hotel firms' financial stability during this turbulent time; particularly the negative impacts caused by government restrictions on both domestic and international travel. The benefit of low debt levels is more pronounced for more vulnerable hotels such as small, less diversified, and slow growing hotel firms. Also, hotel firms that have less long-term debt are more financial stable and resilient during pandemic period. Research outcomes suggest that financial management, in particular capital structure policies should be a critical part of hotel resilience building and crisis management strategy for hotel firms.

Enzymatic glycoengineering-based spin labelling of cell surface sialoglycans to enable their analysis by electron paramagnetic resonance (EPR) spectroscopy.

A novel method for spin labelling of sialoglycans on the cell surface is described. C9-Azido sialic acid was linked to glycans on live cells via CSTII-catalysed α2,3-sialylation utilizing azido-sialic acid nucleotide as a sialyl donor, which was followed by attachment of a spin label to the azide via click reaction. It enables the study of cell surface sialoglycans by EPR spectroscopy.

Characterizing Ryan White Part A-funded support service utilization patterns and their association with viral suppression among people with HIV in New York City.

Use of HIV-related support services has been demonstrated to improve outcomes for people living with HIV. Further exploring patterns of use could help identify how and in what settings additional HIV care and treatment adherence support could be provided. We aimed to identify support service utilization patterns and examine their association with viral load suppression (VLS). Our sample comprised 6,581 people with HIV who received Ryan White Part A support services for basic needs (food and nutrition, legal, harm reduction, housing services) in New York City from 1/2013 to 12/2016, but had not received services specifically targeting HIV care and treatment adherence. Five support service utilization classes were identified using latent class analysis, the majority of which were characterized by the predominant use of concrete services (e.g., food assistance). Compared with the low-intensity, sporadic concrete service use class, clients in all other classes had lower odds of VLS in a 365-day follow-up period, but this disadvantage disappeared with adjustment for confounding variables indicative of need. Our findings underscore the impact of need-related barriers on VLS and suggest that long-term service utilization beyond the one year period of this study may be required to diminish their negative effect on HIV outcomes.

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.

Aerobic vaginitis in the third trimester and its impact on pregnancy outcomes.

BACKGROUND: Aerobic vaginitis (AV) is a vaginal inflammation characterized by disruption of the lactobacillus microbiota and increased counts of different aerobic bacteria. AV may result in severe complications, especially during pregnancy, including preterm delivery, neonatal and maternal infections. This study aimed to determine the prevalence of AV in the third trimester of pregnancy, and the relationship between AV and pregnancy outcomes.  METHODS: A cross-sectional descriptive study included 323 pregnant women attending for routine antenatal care in the Hue University Hospital. Vaginal samples collected at the third trimester of pregnancy were evaluated for AV according to the scoring system of Donders and cultured for identification of predominant bacteria. Pregnancy was followed to its end, and pregnancy outcomes were recorded for both mothers and infants. RESULTS: The proportion of pregnant women diagnosed with AV in the third trimester was found to be 15.5%, with the vast majority of the cases (84%) displaying the light AV and 16% the moderate AV. The vaginal cultures in the women with AV revealed most frequently Streptococcus agalactiae (6%), followed by Enterococcus spp (4%), Staphylococcus aureus (4%), and Acinetobacter baumannii (2%). In addition, AV during the last trimester of pregnancy was associated with an increased risk of puerperal sepsis (OR 8.65, 95% CI: 1.41-53.16, p = 0.020) and there was a slightly increased risk for neonatal infections, which was statistically insignificant. CONCLUSIONS: The proportion of AV is relatively high in Vietnamese pregnant women. Since it is associated with an increased risk of puerperal sepsis, it needs to be diagnosed and treated before delivery.

Gram-scale synthesis of electrochemically oxygenated graphene nanosheets for removal of methylene blue from aqueous solution.

In this study, oxygenated graphene nanosheets (OGNs) were successfully synthesized using a simple electrochemical exfoliation approach and applied to remove methylene blue (MB) in an aqueous solution. The surface morphology and structure of the OGNs were characterized by scanning electron microscopy, transmission electron microscopy, Raman, and x-ray photoelectron spectroscopy. The adsorption performance of OGNs towards aqueous MB was tested by batch experiments. Results showed that a large number of functional groups in OGNs enhanced the removal of MB from the aqueous solution due to the electrostatic interactions between the electrochemically oxygenated groups (e.g. C-OH, C-O, and C=O) and dye molecules. Using Langmuir adsorption isotherm, the maximum MB adsorption capacity (q max) was determined as high as 476.19 mg g-1. These results suggested that the as-prepared OGNs is an effective and promising adsorbent for removing MB, which could be studied extensively for color removal in wastewater treatment.

RWRMTN: a tool for predicting disease-associated microRNAs based on a microRNA-target gene network.

BACKGROUND: The misregulation of microRNA (miRNA) has been shown to cause diseases. Recently, we have proposed a computational method based on a random walk framework on a miRNA-target gene network to predict disease-associated miRNAs. The prediction performance of our method is better than that of some existing state-of-the-art network- and machine learning-based methods since it exploits the mutual regulation between miRNAs and their target genes in the miRNA-target gene interaction networks. RESULTS: To facilitate the use of this method, we have developed a Cytoscape app, named RWRMTN, to predict disease-associated miRNAs. RWRMTN can work on any miRNA-target gene network. Highly ranked miRNAs are supported with evidence from the literature. They then can also be visualized based on the rankings and in relationships with the query disease and their target genes. In addition, automation functions are also integrated, which allow RWRMTN to be used in workflows from external environments. We demonstrate the ability of RWRMTN in predicting breast and lung cancer-associated miRNAs via workflows in Cytoscape and other environments. CONCLUSIONS: Considering a few computational methods have been developed as software tools for convenient uses, RWRMTN is among the first GUI-based tools for the prediction of disease-associated miRNAs which can be used in workflows in different environments.

Conformational landscape of non-B variants of HIV-1 protease: A pulsed EPR study.

HIV infection is a global health epidemic with current FDA-approved HIV-1 Protease inhibitors (PIs) designed against subtype B protease, yet they are used in HIV treatment world-wide regardless of patient HIV classification. In this study, double electron-electron resonance (DEER) electron paramagnetic resonance (EPR) spectroscopy was utilized to gain insights in how natural polymorphisms in several African and Brazilian protease (PR) variants affect the conformational landscape both in the absence and presence of inhibitors. Findings show that Subtypes F and H HIV-1 PR adopt a primarily closed conformation in the unbound state with two secondary mutations, D60E and I62V, postulated to be responsible for the increased probability for closed conformation. In contrast, subtype D, CRF_AG, and CRF_BF HIV-1 PR adopt a primarily semi-open conformation, as observed for PI-naïve-subtype B when unbound by substrate or inhibitor. The impact that inhibitor binding has on shifting the conformational land scape of these variants is also characterized, where analysis provides classification of inhibitor induced shifts away from the semi-open state into weak, moderate and strong effects. The findings are compared to those for prior studies of inhibitor induced conformational shifts in PI-naïve Subtype B, C and CRF_AE.

Relationship between autoantibodies to erythropoietin receptor and renal outcome in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Purpose: We examined the relationship between autoantibodies to erythropoietin receptor (EPOR) and renal outcome in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Materials and methods: Sixty-three Japanese patients with AAV were enrolled and followed for a median of 31.4 months. Patients were screened for serum anti-EPOR antibodies using an enzyme-linked immunosorbent assay. Associations of anti-EPOR antibodies with clinical parameters were analyzed using logistic-regression models.Results: Anti-EPOR antibodies were detected in 7 (11%) of the 63 patients, and levels of the antibodies decreased with immunosuppressive therapy. The presence of anti-EPOR antibodies was associated with a higher Birmingham vasculitis activity score. In addition, anti-EPOR antibodies were more frequently observed in patients with renal outcomes, which was defined as a sustained 50% reduction in the estimated glomerular filtration rate from baseline, than in those without. Multiple logistic regression analysis revealed that presence of anti-EPOR antibodies, as well as age at disease onset, were as risk factors for the renal outcome.Conclusion: Anti-EPOR antibodies were associated with the progression of renal dysfunction in patients with AAV.

A novel circular ssDNA virus of the phylum Cressdnaviricota discovered in metagenomic data from otter clams (Lutraria rhynchaena).

In this study, we present an analysis of metagenome sequences obtained from a filtrate of a siphon tissue homogenate of otter clams (Lutraria rhynchaena) with swollen-siphon disease. The viral signal was mined from the metagenomic data, and a novel circular ssDNA virus was identified. Genomic features and phylogenetic analysis showed that the virus belongs to the phylum Cressdnaviricota, which consists of viruses with circular, single-stranded DNA (ssDNA) genomes. Members of this phylum have been identified in various species and in environmental samples. The newly found virus is distantly related to the currently known members of the phylum Cressdnaviricota.

Design and synthesis of Coenzyme A analogues as Aurora kinase A inhibitors: An exploration of the roles of the pyrophosphate and pantetheine moieties.

Coenzyme A (CoA) is a highly selective inhibitor of the mitotic regulatory enzyme Aurora A kinase, with a novel mode of action. Herein we report the design and synthesis of analogues of CoA as inhibitors of Aurora A kinase. We have designed and synthesised modified CoA structures as potential inhibitors, combining dicarbonyl mimics of the pyrophosphate group with a conserved adenosine headgroup and different length pantetheine-based tail groups. An analogue with a -SH group at the end of the pantotheinate tail showed the best IC50, probably due to the formation of a covalent bond with Aurora A kinase Cys290.

A genome-wide association study reveals the quantitative trait locus and candidate genes that regulate phosphate efficiency in a Vietnamese rice collection.

The crucial role of phosphate (Pi) for plant alongside the expected depletion of non-renewable phosphate rock have created an urgent need for phosphate-efficient rice varieties. In this study, 157 greenhouse-grown Vietnamese rice landraces were treated under Pi-deficient conditions to discover the genotypic variation among biochemical traits, including relative efficiency of phosphorus use (REP), relative root to shoot weight ratio (RRSR), relative physiological phosphate use efficiency (RPPUE), and relative phosphate uptake efficiency (RPUpE). Plants were grown in Yoshida nutrient media with either a full (320 µM) or a low Pi supply (10 µM) over six weeks. This genome-wide association study led to the discovery of 31 significant single nucleotide polymorphisms, 18 quantitative trait loci (QTLs), and 85 candidate genes. A common QTL named qRPUUE9.16 was found among the three investigated traits. Some interesting candidate genes, such as PLASMA MEMBRANE PROTEIN1 (OsPM1), CALMODULIN-RELATED CALCIUM SENSOR PROTEIN 15 (OsCML15), phosphatases 2C (PP2C), STRESS-ACTIVATED PROTEIN KINASE (OsSAPK2), and GLYCEROPHOSPHORYL DIESTER PHOSPHODIESTERASES (GDPD13), were found strongly correlated to the Pi starvation. RNA sequencing transcriptomes revealed that 45 out of 85 candidate genes were significantly regulated under Pi starvation. Furthermore, nearly two-thirds of genotypes did not possess the OsPsTOL1 gene; however, no significant difference was observed in response to Pi deficiency between genotypes with or without this gene, suggesting that other QTLs in rice may resist Pi starvation. These results provide new information on the genetics of nutrient use efficiency in rice and may potentially assist with developing more phosphate-efficient rice plants.

SATQPCR: Website for statistical analysis of real-time quantitative PCR data.

SATQPCR is a web tool providing statistical analysis of real-time quantitative PCR data including all MIQE rules (gene efficiency, selection of reference genes and normalization with them). Our application is a quick tool that provides to the biologist, graphs as well as statistical tables summarizing their results with the chosen methods (t-test or ANOVA with Tukey test). The application is available at http://satqpcr.sophia.inra.fr with a demo dataset. Source code can be found at https://framagit.org/. SUPPLEMENTARY INFORMATION: Tutorials at http://satqpcr.sophia.inra.fr/cgi/help.cgi.