Reduced genetic diversity and the success of the invasive peacock bass (Cichliformes: Cichlidae) / Diversidade genética reduzida e o sucesso da espécie invasora tucunaré (Cichliformes: Cichlidae)

Abstract Several species of Cichla successfully colonized lakes and reservoirs of Brazil, since the 1960's, causing serious damage to local wildlife. In this study, 135 peacock bass were collected in a reservoir complex in order to identify if they represented a single dominant species or multiple ones, as several Cichla species have been reported in the basin. Specimens were identified by color pattern, morphometric and meristic data, and using mitochondrial markers COI, 16S rDNA and Control Region (CR). Overlapping morphological data and similar coloration patterns prevented their identification using the taxonomic keys to species identification available in the literature. However, Bayesian and maximum likelihood from sequencing data demonstrated the occurrence of a single species, Cichla kelberi. A single haplotype was observed for the 16S and CR, while three were detected for COI, with a dominant haplotype present in 98.5% of the samples. The extreme low diversity of the transplanted C. kelberi evidenced a limited number of founding maternal lineages. The success of this colonization seems to rely mainly on abiotic factors, such as increased water transparency of lentic environments that favor visual predators that along with the absence of predators, have made C. kelberi a successful invader of these reservoirs.

Resumo Muitas espécies de Cichla colonizaram com sucesso lagos e reservatórios do Brasil desde os anos 1960, causando graves prejuízos à vida selvagem nesses locais. Neste estudo, 135 tucunarés foram coletados em um complexo de reservatórios a fim de identificar se representavam uma espécie dominante ou múltiplas espécies, uma vez que diversas espécies de Cichla foram registradas na bacia. Os espécimes foram identificados com base na coloração, dados morfométricos e merísticos, e por marcadores mitocondriais COI, 16S rDNA e Região Controle (RC). A sobreposição dos dados morfométricos e o padrão similar de coloração impediram a identificação utilizando as chaves de identificação disponíveis na literatura. Entretanto, as análises bayesiana e de máxima verossimilhança de dados moleculares demonstraram a ocorrência de uma única espécie, Cichla kelberi. Um único haplótipo foi observado para o 16S e RC, enquanto três foram detectados para o COI, com um haplótipo dominante presente em 98,5% das amostras. A baixa diversidade nos exemplares introduzidos de C. kelberi evidenciou um número limitado de linhagens maternas fundadoras. O sucesso da invasão parece depender de fatores abióticos, como a maior transparência da água de ambientes lênticos que favorece predadores visuais que, atrelado à ausência de predadores, fez do C. kelberi um invasor bem-sucedido nesses reservatórios.

Determinants of anemia severity levels among children aged 6-59 months in Ethiopia: Multilevel Bayesian statistical approach.

Anemia is a widespread public health problem that affects all stages of life particularly preschool children and pregnant mothers. Anemia among children had significant impact on their growth, development, school performance and mortality. Different strategies like deworming of young children, vitamin A supplementation for children aged 6-59 months, and ferrous sulphate supplementation and provision of insecticide treated bed net for pregnant women were designed to control and prevent anemia. Also, previous studies on anemia factors were conducted but they were not considering the ordered nature of anemia. Therefore, this study aimed to identify the factors of anemia severity levels among children aged 6-59 months in Ethiopia by using ordinal analysis based on Bayesian hierarchical statistical approach. A secondary data analysis was conducted using the 2016 Ethiopian Demographic and Health Survey data. A total of 8483 weighted children were included. Due to the ordered nature of the anemia and nested nature of DHS data, ordinal logistic regression model based on hierarchical Bayesian statistical approach was employed to identify the determinants of anemia severity levels. In this study, moderate anemia level was found to be the commonest type which accounts around 29.4%. Female children, poorer, middle, and richest wealth index, primary maternal education and having ANC visit had lower risk of having higher order of anemia. Moderate maternal anemia and stunted children had higher chance of having higher order of anemia. Children age had significant different effect on mild and moderate anemia. Meanwhile, multiple birth/s and deworming had effect on moderate anemia. In addition, normal birth weight had also significant and different effect on mild and severe anemia and history of feverlike illness on mild anemia. The prevalence of anemia among children aged 6-59 months anemia was found to be a severe public health problem. Children age, sex, maternal education, child stunting, history of fever, multiple birth, birth weight, provision of deworming and maternal anemia was found to be the most important factors for child anemia severity levels. Therefore, intervention efforts to control and prevent anemia in Ethiopia requires targeting of these hindering factors.

Predicting metastasis in gastric cancer patients: machine learning-based approaches.

Gastric cancer (GC), with a 5-year survival rate of less than 40%, is known as the fourth principal reason of cancer-related mortality over the world. This study aims to develop predictive models using different machine learning (ML) classifiers based on both demographic and clinical variables to predict metastasis status of patients with GC. The data applied in this study including 733 of GC patients, divided into a train and test groups at a ratio of 8:2, diagnosed at Taleghani tertiary hospital. In order to predict metastasis in GC, ML-based algorithms, including Naive Bayes (NB), Random Forest (RF), Support Vector Machine (SVM), Neural Network (NN), Decision Tree (RT) and Logistic Regression (LR), with 5-fold cross validation were performed. To assess the model performance, F1 score, precision, sensitivity, specificity, area under the curve (AUC) of receiver operating characteristic (ROC) curve and precision-recall AUC (PR-AUC) were obtained. 262 (36%) experienced metastasis among 733 patients with GC. Although all models have optimal performance, the indices of SVM model seems to be more appropiate (training set: AUC: 0.94, Sensitivity: 0.94; testing set: AUC: 0.85, Sensitivity: 0.92). Then, NN has the higher AUC among ML approaches (training set: AUC: 0.98; testing set: AUC: 0.86). The RF of ML-based models, which determine size of tumor and age as two essential variables, is considered as the third efficient model, because of higher specificity and AUC (84% and 87%). Based on the demographic and clinical characteristics, ML approaches can predict the metastasis status in GC patients. According to AUC, sensitivity and specificity in both SVM and NN can be regarded as better algorithms among 6 applied ML-based methods.

Top-down and bottom-up effects modulate species co-existence in a context of top predator restoration.

Mesopredators abundance is often limited by top-order predators and also by key food resources. However, the contribution of these bidirectional forces to structure carnivore community is still unclear. Here, we studied how the presence and absence of an apex predator which is currently recovering its former distribution range, the Iberian lynx (Lynx pardinus), determined the absolute abundance and fine-scale spatiotemporal avoidance mechanisms of two sympatric mesocarnivores (stone marten Martes foina and common genet Genetta genetta) with different dietary plasticity. We hypothesized that the lynx causes a mesopredator suppression and subordinate predators develop segregation strategies in respect to their trophic niche breadth. We placed 120 camera-traps in Southern Spain for 8 months in two consecutive years to estimate mesocarnivore abundances by using SCR Bayesian models, prey availability and assess spatio-temporal patterns. We found that the lynx reduced mesocarnivore abundance up to 10 times. Stone marten, a mesopredator with a broad food resources spectrum, showed a total spatial exclusion with the apex predator. Meanwhile, fine-scale avoidance mechanisms allowed the genet to persist in low density inside lynx territories, probably taking advantage of high availability of its preferred prey. Thus, the strength of these top-down and bottom-up effects was rather species-specific. Given the recent recovery of large carnivore populations worldwide, variation in suppression levels on different mesopredator species could modify ecosystem functions provided by the carnivore community in contrasting ways.

Exploring the ATN classification system using brain morphology.

BACKGROUND: The NIA-AA proposed amyloid-tau-neurodegeneration (ATN) as a classification system for AD biomarkers. The amyloid cascade hypothesis (ACH) implies a sequence across ATN groups that patients might undergo during transition from healthy towards AD: A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+. Here we assess the evidence for monotonic brain volume decline for this particular (amyloid-conversion first, tau-conversion second, N-conversion last) and alternative progressions using voxel-based morphometry (VBM) in a large cross-sectional MRI cohort. METHODS: We used baseline data of the DELCODE cohort of 437 subjects (127 controls, 168 SCD, 87 MCI, 55 AD patients) which underwent lumbar puncture, MRI scanning, and neuropsychological assessment. ATN classification was performed using CSF-Aß42/Aß40 (A+/-), CSF phospho-tau (T+/-), and adjusted hippocampal volume or CSF total-tau (N+/-). We compared voxel-wise model evidence for monotonic decline of gray matter volume across various sequences over ATN groups using the Bayesian Information Criterion (including also ROIs of Braak stages). First, face validity of the ACH transition sequence A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+ was compared against biologically less plausible (permuted) sequences among AD continuum ATN groups. Second, we evaluated evidence for 6 monotonic brain volume progressions from A-T-N- towards A+T+N+ including also non-AD continuum ATN groups. RESULTS: The ACH-based progression A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+ was consistent with cognitive decline and clinical diagnosis. Using hippocampal volume for operationalization of neurodegeneration (N), ACH was most evident in 9% of gray matter predominantly in the medial temporal lobe. Many cortical regions suggested alternative non-monotonic volume progressions over ACH progression groups, which is compatible with an early amyloid-related tissue expansion or sampling effects, e.g., due to brain reserve. Volume decline in 65% of gray matter was consistent with a progression where A status converts before T or N status (i.e., ACH/ANT) when compared to alternative sequences (TAN/TNA/NAT/NTA). Brain regions earlier affected by tau tangle deposition (Braak stage I-IV, MTL, limbic system) present stronger evidence for volume decline than late Braak stage ROIs (V/VI, cortical regions). Similar findings were observed when using CSF total-tau for N instead. CONCLUSION: Using the ATN classification system, early amyloid status conversion (before tau and neurodegeneration) is associated with brain volume loss observed during AD progression. The ATN system and the ACH are compatible with monotonic progression of MTL atrophy. TRIAL REGISTRATION: DRKS00007966, 04/05/2015, retrospectively registered.

Maternal immunisation against Group B Streptococcus: A global analysis of health impact and cost-effectiveness.

BACKGROUND: Group B Streptococcus (GBS) can cause invasive disease (iGBS) in young infants, typically presenting as sepsis or meningitis, and is also associated with stillbirth and preterm birth. GBS vaccines are under development, but their potential health impact and cost-effectiveness have not been assessed globally. METHODS AND FINDINGS: We assessed the health impact and value (using net monetary benefit (NMB), which measures both health and economic effects of vaccination into monetary units) of GBS maternal vaccination in an annual cohort of 140 million pregnant women across 183 countries in 2020. Our analysis uses a decision tree model, incorporating risks of GBS-related health outcomes from an existing Bayesian disease burden model. We extrapolated country-specific GBS-related healthcare costs using data from a previous systematic review and calculated quality-adjusted life years (QALYs) lost due to infant mortality and long-term disability. We assumed 80% vaccine efficacy against iGBS and stillbirth, following the WHO Preferred Product Characteristics, and coverage based on the proportion of pregnant women receiving at least 4 antenatal visits. One dose was assumed to cost $50 in high-income countries, $15 in upper-middle income countries, and $3.50 in low-/lower-middle-income countries. We estimated NMB using alternative normative assumptions that may be adopted by policymakers. Vaccinating pregnant women could avert 127,000 (95% uncertainty range 63,300 to 248,000) early-onset and 87,300 (38,100 to 209,000) late-onset infant iGBS cases, 31,100 deaths (14,400 to 66,400), 17,900 (6,380 to 49,900) cases of moderate and severe neurodevelopmental impairment, and 23,000 (10,000 to 56,400) stillbirths. A vaccine effective against GBS-associated prematurity might also avert 185,000 (13,500 to 407,000) preterm births. Globally, a 1-dose vaccine programme could cost $1.7 billion but save $385 million in healthcare costs. Estimated global NMB ranged from $1.1 billion ($-0.2 to 3.8 billion) under the least favourable normative assumptions to $17 billion ($9.1 to 31 billion) under the most favourable normative assumptions. The main limitation of our analysis was the scarcity of data to inform some of the model parameters such as those governing health-related quality of life and long-term costs from disability, and how these parameters may vary across country contexts. CONCLUSIONS: In this study, we found that maternal GBS vaccination could have a large impact on infant morbidity and mortality. Globally, a GBS maternal vaccine at reasonable prices is likely to be a cost-effective intervention.

Genetic variation and demographic history of Sudan desert sheep reveal two diversified lineages.

More than 400 million sheep are raised on the African continent, the majority of which are indigenous and are primarily reared for sustenance. They have effectively adapted to various climatic and production environments, surviving and flourishing. The genetic relationships among these sheep populations remain understudied. Herein, we sequenced the entire mitochondrial DNA control region of 120 animals from Hamary and Kabashi and their crossbreed (Hamary x Kabashi) of Sudan desert sheep (SDS) to understand their maternal-inherited genetic variation and demographic history profiles and relate those to the history of sheep pastoralism on the African continent. The results show a diversified and predominant D- loop haplogroup B (n = 102, 85%), with all other sequences belonging to haplogroup A. Most of the maternal genetic variation was partitioned between haplogroup (76.3%) while within haplogroup accounted for 23.7% of the variation. However, little genetic differentiation was observed among the two breeds and their crosses, with our results supporting a Hamari maternal origin for the crossbreed. Bayesian coalescent-based analysis reveals distinct demographic history between the two haplogroups, two breeds and their crosses. Comparison of the two haplogroup showed that haplogroup B experienced an earlier expansion than haplogroup A. Unlike the breed-based comparison, the expansion of the two breeds started roughly at the same time, around 6500 years ago, with Kabashi having a slightly greater effective population size. The maternal ancestors of SDS may have diverged before their introduction to the African continent. This study provides novel insights into the early history of these two main breeds of Sudan desert sheep and their crosses.

Relationships between circulating metabolites and facial skin aging: a Mendelian randomization study.

BACKGROUND: Blood metabolites are important to various aspects of our health. However, currently, there is little evidence about the role of circulating metabolites in the process of skin aging. OBJECTIVES: To examine the potential effects of circulating metabolites on the process of skin aging. METHOD: In the primary analyses, we applied several MR methods to study the associations between 249 metabolites and facial skin aging risk. In the secondary analyses, we replicated the analyses with another array of datasets including 123 metabolites. MR Bayesian model averaging (MR-BMA) method was further used to prioritize the metabolites for the identification of predominant metabolites that are associated with skin aging. RESULTS: In the primary analyses, only the unsaturation degree of fatty acids was found significantly associated with skin aging with the IVW method after multiple testing (odds ratio = 1.084, 95% confidence interval = 1.049-1.120, p = 1.737 × 10-06). Additionally, 11 out of 17 unsaturation-related biomarkers showed a significant or suggestively significant causal effect [p < 0.05 and > 2 × 10-4 (0.05/249 metabolites)]. In the secondary analyses, seven metabolic biomarkers were found significantly associated with skin aging [p < 4 × 10-4 (0.05/123)], while six of them were related to the unsaturation degree. MR-BMA method validated that the unsaturation degree of fatty acids plays a dominant role in facial skin aging. CONCLUSIONS: Our study used systemic MR analyses and provided a comprehensive atlas for the associations between circulating metabolites and the risk of facial skin aging. Genetically proxied unsaturation degree of fatty acids was highlighted as a dominant factor correlated with the risk of facial skin aging.

Hotspots of un-iodized salt availability among Ethiopian households, evidence from the national survey data.

BACKGROUND: Universal salt iodization was started before decades but there are communities using the un-iodized salt till now. More than one-tenth of the Ethiopian community uses un-iodized salt. OBJECTIVE: This study aimed to identify the hotspots and associate factors of un-iodized salt availability in Ethiopia based on Ethiopian national household survey data. METHODS: We conducted an in-depth analysis of the Ethiopian Demographic and Health Survey 2016 data. A total of 15,567 households were included in the final analysis. We cleaned and weighed the data using Stata version 16 software and descriptive outputs were reported in graphs and tables. We computed the weighted prevalence of un-iodized salt and prepared it for spatial analysis. Global-level spatial autocorrelation, hotspot analysis using the Getis-Ord Gi* statistics, and spatial interpolation using empirical Bayesian interpolation were executed using ArcGIS 10.3 to predict the magnitude of un-iodized salt at the national level. The binary logistics regression model was used to identify the contributing factors of un-iodized salt utilization. Model goodness of fit was tested with Hosmer and Lemeshow goodness-of-fit test (P = 0.96). Finally, the adjusted odds ratio (AOR) with 95% CI was reported to identify significant factors. RESULTS: The magnitude of un-iodized salt availability was 14.19% (95% CI: 13.65, 14.75) among Ethiopian households. Un-iodized salt hotspots were found in Afar, Somalia, and Benishangul Gumuz regions. Compared to poorest wealth index: poorer (AOR = 0.55, 95% CI: 0.48, 0.64), middle (AOR = 0.51, 95% CI: 0.44, 0.60), richer (AOR = 0.55, 95% CI: 0.47, 0.64), and richest (AOR = 0.61, 95% CI: 0.50, 0.75); compared to uneducated household head: heads with secondary (AOR = 0.72, 95% CI: 0.60, 0.67) and above secondary (AOR = 0.54, 95% CI: 0.43, 0.67) education reduced the odds of un-iodized salt viability, while households living in highland (AOR = 1.16, 95% CI: 1.05, 1.29) had increased the odds of un-iodized salt availability. CONCLUSION: More than a tenth of the households in Ethiopia uses un-iodized salt. Hotspots of un-iodized salt availability were found in Somali and Afar regions of Ethiopia. Better wealth index and education of the household heads reduces the odds of un-iodized salt availability while living in a high altitude above 2200 m increases the odds of un-iodized salt availability in Ethiopia.

Integrative analysis of multi-omics and imaging data with incorporation of biological information via structural Bayesian factor analysis.

MOTIVATION: With the rapid development of modern technologies, massive data are available for the systematic study of Alzheimer's disease (AD). Though many existing AD studies mainly focus on single-modality omics data, multi-omics datasets can provide a more comprehensive understanding of AD. To bridge this gap, we proposed a novel structural Bayesian factor analysis framework (SBFA) to extract the information shared by multi-omics data through the aggregation of genotyping data, gene expression data, neuroimaging phenotypes and prior biological network knowledge. Our approach can extract common information shared by different modalities and encourage biologically related features to be selected, guiding future AD research in a biologically meaningful way. METHOD: Our SBFA model decomposes the mean parameters of the data into a sparse factor loading matrix and a factor matrix, where the factor matrix represents the common information extracted from multi-omics and imaging data. Our framework is designed to incorporate prior biological network information. Our simulation study demonstrated that our proposed SBFA framework could achieve the best performance compared with the other state-of-the-art factor-analysis-based integrative analysis methods. RESULTS: We apply our proposed SBFA model together with several state-of-the-art factor analysis models to extract the latent common information from genotyping, gene expression and brain imaging data simultaneously from the ADNI biobank database. The latent information is then used to predict the functional activities questionnaire score, an important measurement for diagnosis of AD quantifying subjects' abilities in daily life. Our SBFA model shows the best prediction performance compared with the other factor analysis models. AVAILABILITY: Code are publicly available at https://github.com/JingxuanBao/SBFA. CONTACT: qlong@upenn.edu.

Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. OBJECTIVES: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. METHODS: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. RESULTS: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of ß=-0.15 [95% confidence interval (CI): -0.27, -0.03], ß=-0.14 (95% CI: -0.28, -0.002), ß=-0.22 (95% CI: -0.23, -0.10), ß=-0.06 (95% CI: -0.18, 0.06), and ß=-0.25 (95% CI: -0.37, -0.14), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: ORPFNA=0.56 (95% CI: 0.38, 0.83), ORPFDA=0.52 (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [-0.28; 95% highest posterior density (HPD): -0.44, -0.14] and decreased odds of large-for-gestational-age (OR=0.49; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. DISCUSSION: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723.

Nutritional Modulation of Associations between Prenatal Exposure to Persistent Organic Pollutants and Childhood Obesity: A Prospective Cohort Study.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations. OBJECTIVES: The main objective was to characterize the joint associations and interactions between prenatal levels of POPs and nutrients on childhood obesity. METHODS: We used data from to the Spanish INfancia y Medio Ambiente-Environment and Childhood (INMA) birth cohort, on POPs and nutritional biomarkers measured in maternal blood collected at the first trimester of pregnancy and child anthropometric measurements at 7 years of age. Six organochlorine compounds (OCs) [dichlorodiphenyldichloroethylene, hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH) and polychlorinated biphenyls 138, 153, 180] and four per- and polyfluoroalkyl substances (PFAS) were measured. Nutrients included vitamins (D, B12, and folate), polyunsaturated fatty acids (PUFAs), and dietary carotenoids. Two POPs-nutrients mixtures data sets were established: a) OCs, PFAS, vitamins, and carotenoids (n=660), and b) OCs, PUFAs, and vitamins (n=558). Joint associations of mixtures on obesity were characterized using Bayesian kernel machine regression (BKMR). Relative importance of biomarkers and two-way interactions were identified using gradient boosting machine, hierarchical group lasso regularization, and BKMR. Interactions were further characterized using multivariate regression models in the multiplicative and additive scale. RESULTS: Forty percent of children had overweight or obesity. We observed a positive overall joint association of both POPs-nutrients mixtures on overweight/obesity risk, with HCB and vitamin B12 the biomarkers contributing the most. Recurrent interactions were found between HCB and vitamin B12 across screening models. Relative risk for a natural log increase of HCB was 1.31 (95% CI: 1.11, 1.54, pInteraction=0.02) in the tertile 2 of vitamin B12 and in the additive scale a relative excess risk due to interaction of 0.11 (95% CI: 0.02, 0.20) was found. Interaction between perfluorooctane sulfonate and ß-cryptoxanthin suggested a protective effect of the antioxidant on overweight/obesity risk. CONCLUSION: These results support that maternal nutritional status may modulate the effect of prenatal exposure to POPs on childhood overweight/obesity. These findings may help to develop a biological hypothesis for future toxicological studies and to better interpret inconsistent findings in epidemiological studies. https://doi.org/10.1289/EHP11258.

Complete chloroplast genome sequences of Myristicaceae species with the comparative chloroplast genomics and phylogenetic relationships among them.

BACKGROUND: Myristicaceae was widly distributed from tropical Asia to Oceania, Africa, and tropical America. There are 3 genera and 10 species of Myristicaceae present in China, mainly distributed in the south of Yunnan Province. Most research on this family focuses on fatty acids, medicine, and morphology. Based on the morphology, fatty acid chemotaxonomy, and a few of molecular data, the phylogenetic position of Horsfieldia pandurifolia Hu was controversial. RESULTS: In this study, the chloroplast genomes of two Knema species, Knema globularia (Lam.) Warb. and Knema cinerea (Poir.) Warb., were characterized. Comparing the genome structure of these two species with those of other eight published species, including three Horsfieldia species, four Knema species, and one Myristica species, it was found that the chloroplast genomes of these species were relatively conserved, retaining the same gene order. Through sequence divergence analysis, there were 11 genes and 18 intergenic spacers were subject to positive selection, which can be used to analyze the population genetic structure of this family. Phylogenetic analysis showed that all Knema species were clustered in the same group and formed a sister clade with Myristica species support by both high maximum likelihood bootstrap values and Bayesian posterior probabilities; among Horsfieldia species, Horsfieldia amygdalina (Wall.) Warb., Horsfieldia kingii (Hook.f.) Warb., Horsfieldia hainanensis Merr. and Horsfieldia tetratepala C.Y.Wu. were grouped together, but H. pandurifolia formed a single group and formed a sister clade with genus Myristica and Knema. Through the phylogenetic analysis, we support de Wilde' view that the H. pandurifolia should be separated from Horsfieldia and placed in the genus Endocomia, namely Endocomia macrocoma subsp. prainii (King) W.J.de Wilde. CONCLUSION: The findings of this study provide a novel genetic resources for future research in Myristicaceae and provide a molecular evidence for the taxonomic classification of Myristicaceae.

Conformational and oligomeric states of SPOP from small-angle X-ray scattering and molecular dynamics simulations.

Speckle-type POZ protein (SPOP) is a substrate adaptor in the ubiquitin proteasome system, and plays important roles in cell-cycle control, development, and cancer pathogenesis. SPOP forms linear higher-order oligomers following an isodesmic self-association model. Oligomerization is essential for SPOP's multivalent interactions with substrates, which facilitate phase separation and localization to biomolecular condensates. Structural characterization of SPOP in its oligomeric state and in solution is, however, challenging due to the inherent conformational and compositional heterogeneity of the oligomeric species. Here, we develop an approach to simultaneously and self-consistently characterize the conformational ensemble and the distribution of oligomeric states of SPOP by combining small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations. We build initial conformational ensembles of SPOP oligomers using coarse-grained molecular dynamics simulations, and use a Bayesian/maximum entropy approach to refine the ensembles, along with the distribution of oligomeric states, against a concentration series of SAXS experiments. Our results suggest that SPOP oligomers behave as rigid, helical structures in solution, and that a flexible linker region allows SPOP's substrate-binding domains to extend away from the core of the oligomers. Additionally, our results are in good agreement with previous characterization of the isodesmic self-association of SPOP. In the future, the approach presented here can be extended to other systems to simultaneously characterize structural heterogeneity and self-assembly.

Clinical profiling of end-stage heart failure with preserved ejection fraction: The National Readmission Database.

BACKGROUND: End-stage (Stage D) heart failure with preserved ejection fraction (HFpEF) is a poorly characterized syndrome that has heterogeneous underlying pathophysiology. A better characterization of the various clinical profiles of Stage D HFpEF is needed. METHOD: 1066 patients with Stage D HFpEF were selected from National Readmission Database. A Bayesian clustering algorithm based on a Dirichlet process mixture model was implemented. Cox proportional hazard regression model was used to relate the risk of in-hospital mortality with each identified clinical cluster. RESULT: 4 distinct clinical clusters were recognized. Group 1 had a higher prevalence of obesity (84.5%) and sleep disorders (62.0%). Group 2 had a higher prevalence of diabetes mellitus (92%), chronic kidney disease (98.3%), anemia (72.6%), and coronary artery disease (59.0%). Group 3 had a higher prevalence of advanced age (82.1%), hypothyroidism (28.9%), dementia (17.0%), atrial fibrillation (63.8%) and valvular disease (30.5%) and Group 4 had a higher prevalence of liver disease (44.5%), right-sided HF (20.2%) and amyloidosis (4.5%). During 2019, 193 (18.1%) in-hospital mortality events occurred. Considering Group 1 (with mortality rate of 4.1%) as a reference, the hazard ratio of in-hospital mortality was 5.4 [95% confidence interval (CI): 2.2-13.6] for Group 2, 6.4 (95% CI: 2.6-15.8) for Group 3 and 9.1 (95% CI: 3.5-23.8) for Group 4. CONCLUSION: End-stage HFpEF presents with different clinical profiles with varied upstream causes. This may help provide evidence toward the development of targeted therapies.

Association between polyfluoroalkyl substances exposure and sex steroids in adolescents: The mediating role of serum albumin.

BACKGROUND: Polyfluoroalkyl substances (PFASs) are an emerging class of contaminants with endocrine disrupting hazards. The impact of PFASs exposure on sex steroids remain inconclusive. METHODS: This study used data from the 2013-2016 National Health and Nutrition Examination Survey (NHANES), including 525 adolescents aged 12-19. We explored the association between serum PFASs and sex steroids using multiple linear regression, weighted quantified sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses were performed to assess whether serum albumin mediates the effects of PFASs on sex steroids. RESULTS: Single exposure to perfluorohexane sulfonic acid (PFHxS) or n-perfluorooctanoic acid (n-PFOA) was found to be inversely associated with sex hormone binding protein (SHBG) after adjustment for confounders. Results from both the WQS and BKMR models showed that mixed exposure to the five PFASs was negatively associated with SHBG and testosterone (TT) in all adolescents, while only in the WQS model, the mixed exposure to PFASs was negatively correlated with E2 and FAI in boys and negatively correlated with TT and SHBG in girls. Serum albumin was found to possibly mediate 9.7 % of the association between mixed PFAS exposure and TT, and 9.7 % of the association between mixed PFAS exposure and SHBG. CONCLUSION: Our study demonstrates a negative association between mixed exposure to PFASs and adolescent TT and SHBG levels, and suggests that albumin may merit further study as a potential target for PFAS harm reduction.

Spatiotemporal heterogeneity and impact factors of hepatitis B and C in China from 2010 to 2018: Bayesian space-time hierarchy model.

Introduction: Viral hepatitis is a global public health problem, and China still faces great challenges to achieve the WHO goal of eliminating hepatitis. Methods: This study focused on hepatitis B and C, aiming to explore the long-term spatiotemporal heterogeneity of hepatitis B and C incidence in China from 2010 to 2018 and quantify the impact of socioeconomic factors on their risk through Bayesian spatiotemporal hierarchical model. Results: The results showed that the risk of hepatitis B and C had significant spatial and temporal heterogeneity. The risk of hepatitis B showed a slow downward trend, and the high-risk provinces were mainly distributed in the southeast and northwest regions, while the risk of hepatitis C had a clear growth trend, and the high-risk provinces were mainly distributed in the northern region. In addition, for hepatitis B, illiteracy and hepatitis C prevalence were the main contributing factors, while GDP per capita, illiteracy rate and hepatitis B prevalence were the main contributing factors to hepatitis C. Disussion: This study analyzed the spatial and temporal heterogeneity of hepatitis B and C and their contributing factors, which can serve as a basis for monitoring efforts. Meanwhile, the data provided by this study will contribute to the effective allocation of resources to eliminate viral hepatitis and the design of interventions at the provincial level.

Training in Basic Life Support and Bystander-Performed Cardiopulmonary Resuscitation and Survival in Out-of-Hospital Cardiac Arrests in Denmark, 2005 to 2019.

Importance: Strategies to improve survival from out-of-hospital cardiac arrest (OHCA) include mass education of laypersons with no official duty to respond to OHCA. In Denmark, basic life support (BLS) course attendance has been mandated by law in October 2006 for obtaining a driver's license for all vehicles and in vocational education programs. Objectives: To examine the association between yearly BLS course participation rate and bystander cardiopulmonary resuscitation (CPR) and 30-day survival from OHCA and to examine if bystander CPR rate acted as a mediator on the association between mass education of laypersons in BLS and survival from OHCA. Design, Setting, and Participants: This cohort study included outcomes for all OHCA incidents from the Danish Cardiac Arrest Register between 2005 and 2019. Data concerning BLS course participation were supplied by the major Danish BLS course providers. Main Outcomes and Measures: The main outcome was 30-day survival of patients who experienced OHCA. Logistic regression analysis was used to examine the association between BLS training rate, bystander CPR rate, and survival, and a bayesian mediation analysis was conducted to examine mediation. Results: A total of 51 057 OHCA incidents and 2 717 933 course certificates were included. The study showed that the annual 30-day survival from OHCA increased by 14% (odds ratio [OR], 1.14; 95% CI, 1.10-1.18; P < .001) when BLS course participation rate increased by 5% in analysis adjusted for initial rhythm, automatic external defibrillator use, and mean age. An average mediated proportion of 0.39 (95% QBCI, 0.049-0.818; P = .01). In other words, the last result indicated that 39% of the association between mass educating laypersons in BLS and survival was mediated through an increased bystander CPR rate. Conclusions and Relevance: In this cohort study of Danish BLS course participation and survival, a positive association was found between annual rate of mass education in BLS and 30-day survival from OHCA. The association of BLS course participation rate on 30-day survival was mediated by the bystander CPR rate; approximately 60% of the association of BLS course participation rate on 30-day survival was based on factors other than increased CPR rates.

Estimating genetic parameters of reproductive, carcass, and meat quality traits in Polled Nellore cattle.

Considering the economic and commercial efficiency of the beef production chain, the yield and quality of the meat produced must also be included in breeding programs. For the Nellore breed, including the polled herd, these aspects have not been much studied. The aim of this study was to estimate genetic parameters for scrotal circumference adjusted to 365 (SC365) and 450 (SC450) days of age, age at first calving (AFC), accumulated productivity (AP), stayability (STAY), longissimus muscle area (LMA), thickness of subcutaneous fat over the 12th-13th ribs (BF), thickness of subcutaneous fat over the rump (RF), and shear force measured by Warner-Bratzler shear force (WBSF) of polled Nellore cattle. Bayesian analyses were performed by adopting a linear animal model, whereas STAY analyses used the linear threshold model. Heritability estimates were 0.31 (SC365), 0.37 (SC450), 0.16 (AFC), 0.25 (AP), 0.16 (STAY), 0.30 (LMA), 0.13 (BF), 0.24 (RF), and 0.15 (WBSF), indicating moderate response to selection. Genetic and residual correlations between SC365 and SC450 were high (0.91 and 0.74, respectively), as well as the genetic correlations of AP with SC365, SC450, AFC, and STAY (0.61, 0.62, - 0.69, and 0.83, respectively). Genetic and residual correlations of WBSF with reproductive and carcass characteristics exhibited high standard deviations, however favorable. Based on the results, it is expected that in the medium term, animals with greater sexual precocity will also have greater accumulated productivity and longer permanence of females in the herd, along with superior carcass traits. However, due to the low heritabilities and small genetic associations with reproductive traits, fat thickness characteristics (BF and RF) will still require direct selection.

Study of Bayesian variable selection method on mixed linear regression models.

Variable selection has always been an important issue in statistics. When a linear regression model is used to fit data, selecting appropriate explanatory variables that strongly impact the response variables has a significant effect on the model prediction accuracy and interpretation effect. redThis study introduces the Bayesian adaptive group Lasso method to solve the variable selection problem under a mixed linear regression model with a hidden state and explanatory variables with a grouping structure. First, the definition of the implicit state mixed linear regression model is presented. Thereafter, the Bayesian adaptive group Lasso method is used to determine the penalty function and parameters, after which each parameter's specific form of the fully conditional posterior distribution is calculated. Moreover, the Gibbs algorithm design is outlined. Simulation experiments are conducted to compare the variable selection and parameter estimation effects in different states. Finally, a dataset of Alzheimer's Disease is used for application analysis. The results demonstrate that the proposed method can identify the observation from different hidden states, but the results of the variable selection in different states are obviously different.