Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex and N-terminal pro B-type natriuretic peptide: The potential mediating role of iron biomarkers

Background Levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), a marker of heart failure and cardiovascular risk, are generally higher in women than men. We explored whether iron biomarkers mediate sex differences in NT-proBNP levels. Methods We included 5,343 community-dwelling individuals from the Prevention of Renal and Vascular Endstage Disease study. With linear regression analyses, we investigated the association of sex and iron biomarkers with NT-proBNP levels, independent of adjustment for potential confounders. The assessed iron biomarkers included ferritin, transferrin saturation (TSAT), hepcidin, and soluble transferrin receptor (sTfR). Next, we performed mediation analyses to investigate to which extent iron biomarkers influence the association between sex and NT-proBNP. Results Of the included 5,343 participants, the mean standard deviation age was 52.2 ± 11.6 years and 52% were females. After adjustment for potential confounders, women compared to men, had higher NT-proBNP (β = 0.31; 95%CI = 0.29, 0.34), but lower ferritin (β = –0.37; 95%CI = –0.39, –0.35), hepcidin (β = –0.22, 95%CI = –0.24, –0.20), and TSAT (β = –0.07, 95% CI = –0.08, –0.06). Lower ferritin (β = –0.05, 95%CI = –0.08, –0.02), lower hepcidin (β = –0.04, 95%CI = –0.07, –0.006), and higher TSAT (β = 0.07; 95%CI = 0.01, 0.13) were associated with higher NT-proBNP. In mediation analyses, ferritin and hepcidin explained 6.5 and 3.1% of the association between sex and NT-proBNP, respectively, while TSAT minimally suppressed (1.9%) this association. Conclusion Our findings suggest that iron biomarkers marginally explain sex differences in levels of NT-proBNP. Future studies are needed to explore causality and potential mechanisms underlying these pathways.
Transcriptome analysis of differentially expressed circRNAs miRNAs and mRNAs during the challenge of coccidiosis

Avian coccidiosis is a common enzootic disease caused by infection of Eimeria species parasites. It causes huge economic losses in the global poultry industry. Current control using anticoccidial drugs or vaccination is limited due to drug resistance and the relatively high cost of vaccines. Improving host genetic resistance to Eimeria species is considered an effective strategy for improved control of coccidiosis. Circular RNAs (circRNAs) have been found to function as biomarkers or diagnoses of various kinds of diseases. The molecular biological functions of circRNAs, miRNAs, and mRNAs related to Sasso chicken have not yet been described during Eimeria species challenge. In this study, RNA-seq was used to profile the expression pattern of circRNAs, miRNAs, and mRNAs in spleens from Eimeria tenella-infected and non-infected commercial dual-purpose Sasso T445 breed chickens. Results showed a total of 40 differentially expressed circRNAs (DEcircRNAs), 31 differentially expressed miRNAs (DEmiRNAs), and 820 differentially expressed genes (DEmRNAs) between infected and non-infected chickens. Regulatory networks were constructed between differentially expressed circRNAs, miRNAs, and mRNAs to offer insights into the interaction mechanisms between chickens and Eimeria spp. Functional validation of a significantly differentially expressed circRNA, circMGAT5, revealed that circMGAT5 could sponge miR-132c-5p to promote the expression of the miR-132c-5p target gene monocyte to macrophage differentiation-associated (MMD) during the infection of E. tenella sporozoites or LPS stimulation. Pathologically, knockdown of circMGAT5 significantly upregulated the expression of macrophage surface markers and the macrophage activation marker, F4/80 and MHC-II, which indicated that circMGAT5 might inhibit the activation of macrophage. miR-132c-5p markedly facilitated the expression of F4/80 and MHC-II while circMGAT5 could attenuate the increase of F4/80 and MHC-II induced by miR-132c-5p, indicating that circMGAT5 exhibited function through the circMGAT5-miR-132c-5p-MMD axis. Together, our results indicate that circRNAs exhibit their resistance or susceptive roles during E. tenella infection. Among these, circMGAT5 may inhibit the activation of macrophages through the circMGAT5-miR-132c-5p-MMD axis to participate in the immune response induced by Eimeria infection.
Language input in late infancy scaffolds emergent literacy skills and predicts reading related white matter development

Longitudinal studies provide the unique opportunity to test whether early language provides a scaffolding for the acquisition of the ability to read. This study tests the hypothesis that parental language input during the first 2 years of life predicts emergent literacy skills at 5 years of age, and that white matter development observed early in the 3rd year (at 26 months) may help to account for these effects. We collected naturalistic recordings of parent and child language at 6, 10, 14, 18, and 24 months using the Language ENvironment Analysis system (LENA) in a group of typically developing infants. We then examined the relationship between language measures during infancy and follow-up measures of reading related skills at age 5 years, in the same group of participants (N = 53). A subset of these children also completed diffusion and quantitative MRI scans at age 2 years (N = 20). Within this subgroup, diffusion tractography was used to identify white matter pathways that are considered critical to language and reading development, namely, the arcuate fasciculus (AF), superior and inferior longitudinal fasciculi, and inferior occipital-frontal fasciculus. Quantitative macromolecular proton fraction (MPF) mapping was used to characterize myelin density within these separately defined regions of interest. The longitudinal data were then used to test correlations between early language input and output, white matter measures at age 2 years, and pre-literacy skills at age 5 years. Parental language input, child speech output, and parent-child conversational turns correlated with pre-literacy skills, as well as myelin density estimates within the left arcuate and superior longitudinal fasciculus. Mediation analyses indicated that the left AF accounted for longitudinal relationships between infant home language measures and 5-year letter identification and letter-sound knowledge, suggesting that the left AF myelination at 2 years may serve as a mechanism by which early language experience supports emergent literacy.
Identification of novel recombinants and proposed standard reference genomes for phylogenetic classification of canine parvovirus-2 (CPV-2): Comprehensive analysis revealing global evolutionary trait

Sustained spread and continuous evolution of CPV-2 generate new genetic information; nevertheless, there is no adopted phylogenetic tool, and parvo virologists still refer to the three antigenic variants. Herein, this report attempted to review the evolutionary trait of CPV-2 and proposed standard reference genomes using the Maximum Likelihood-based phylogenetic analysis and Parsimony-Informative Sites. The analysis revealed three main evolutionary pathways where CPV-2 strains cluster into distinct clades depicted as GI, GII, or GIII, respectively. Furthermore, novel CPV-2 natural recombinants were detected, occurring only between the newly identified strains (2017–2020). Those findings provide unique insights into the evolutionary relatedness of CPV-2, clarify discrepancies between different geographic areas and will contribute to achieving a more reliable CPV-2 genetic and evolutionary genotyping classification.
Latent transitions across perceived parental marital conflict and family cohesion profiles in high school students

This study aimed to explore the latent profiles across perceived parental marital conflict and family cohesion, as well as the transition patterns within-person and within-sample profiles over time. We conducted a 1-year follow-up study with a sample of first-year high school students from China. A total of 453 participants were included in the present analysis. We identified the following three latent profiles: high parental conflict and poor family cohesion profile, moderate parental conflict and family cohesion profile, and low parental conflict and good family cohesion profile. Female students and those who not lived with parents together were more likely to perceive more parental marital conflict and less cohesion in the family. The majority of students with high transition probability remained in the same profiles over time. The counts of latent transition pattern also demonstrated that students remaining in the primary profile over time accounted for the large proportion. The present study advances empirical bases for confirming the family system theory’s notion that the family is not static, but dynamic. Findings provide the optimal timing of interventions toward healthy transition.
Host diet shapes functionally differentiated gut microbiomes in sympatric speciation of blind mole rats in Upper Galilee, Israel

The gut microbiome is important for host nutrient metabolism and ecological adaptation. However, how the gut microbiome is affected by host phylogeny, ecology and diet during sympatric speciation remain unclear. Here, we compare and contrast the gut microbiome of two sympatric blind mole rat species and correlate them with their corresponding host phylogeny, ecology soil metagenomes, and diet to determine how these factors may influence their gut microbiome. Our results indicate that within the host microbiome there is no significant difference in community composition, but the functions between the two sympatric species populations vary significantly. No significant correlations were found between the gut microbiome differentiation and their corresponding ecological soil metagenomes and host phylogeny. Functional enrichment analysis suggests that the host diets may account for the functional divergence of the gut microbiome. Our results will help us understand how the gut microbiome changes with corresponding ecological dietary factors in sympatric speciation of blind subterranean mole rats.
Association between serum Klotho concentration and all-cause and cardiovascular mortality among American individuals with hypertension

Background and aims Evidence indicates that serum Klotho concentration is associated with mortality in patients with chronic kidney disease (CKD). However, evidence on this association among people with hypertension is scarce. Therefore, we aimed to examine the association between serum Klotho concentration and all-cause and cardiovascular mortality in American patients with hypertension. Methods and results We included 6,778 participants with hypertension from the National Health and Nutrition Examination Survey (NHANES) 2007–2014. A Cox proportional hazard model was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs). The correlation between serum Klotho concentration and mortality was determined using restricted cubic spline and piecewise linear regression analyses. During 36,714 person-years of follow-up, 575 deaths were documented. Lower serum Klotho concentration was associated with increased all-cause mortality, but not cardiovascular mortality after multivariate adjustment. According to spline analysis, the correlation between serum Klotho concentration and all-cause mortality was non-linear (P < 0.001), and the threshold value was 574 pg/mL. The HR below the threshold point was 0.79 (95% CI: 0.67–0.93); no significant difference was found above the threshold point. Conclusion Higher serum Klotho concentration was associated with lower all-cause mortality, but not cardiovascular mortality in patients with hypertension with or without chronic renal impairment.
Inhibition of microRNA-200c preserves astrocyte sirtuin-1 and mitofusin-2, and protects against hippocampal neurodegeneration following global cerebral ischemia in mice

Memory impairment remains a leading disability in survivors of global cerebral ischemia, occurring secondary to delayed neurodegeneration of hippocampal cornu ammonis-1 (CA1) neurons. MicroRNA-200c (miR-200c) is induced following ischemic stress and we have previously demonstrated that pre-treatment with anti-miR-200c is protective against embolic stroke in mice. In the present study we assessed the role of miR-200c on CA1 neurodegeneration, sirtuin-1 (SIRT1), and mitochondrial dynamic protein expression in a mouse model of transient global cerebral ischemia and in vitro in primary mouse astrocyte cultures after simulated ischemia. Mice were subjected to 10 min bilateral common carotid artery occlusion plus hypotension with 5% isoflurane. After 2 h recovery mice were treated with intravenous injection of either anti-miR-200c or mismatch control. Memory function was assessed by Barnes maze at post-injury days 3 and 7. Mice were sacrificed at post-injury day 7 for assessment of brain cell-type specific expression of miR-200c, SIRT1, and the mitochondrial fusion proteins mitofusin-2 (MFN2) and OPA1 via complexed fluorescent in situ hybridization and fluorescent immunohistochemistry. Global cerebral ischemia induced significant loss of CA1 neurons, impaired memory performance and decreased expression of CA1 SIRT1, MFN2, and OPA1. Post-injury treatment with anti-miR-200c significantly improved survival, prevented CA1 neuronal loss, improved post-injury performance in Barnes maze, and was associated with increased post-injury expression of CA1 SIRT1 and MFN2 in astrocytes. In vitro, primary mouse astrocyte cultures pre-treated with miR-200c inhibitor prior to oxygen/glucose deprivation preserved expression of SIRT1 and MFN2, and decreased reactive oxygen species generation, whereas pre-treatment with miR-200c mimic had opposite effects that could be reversed by co-treatment with SIRT1 activator. These results suggest that miR-200c regulates astrocyte mitochondrial homeostasis via targeting SIRT1, and that CA1 astrocyte mitochondria and SIRT1 represent potential post-injury therapeutic targets to preserve cognitive function in survivors of global cerebral ischemia.
INVESTIGATING THE ORIGIN OF HOT GAS LINES IN HERBIG AE/BE STARS

We analyze high-resolution UV spectra of a small sample of Herbig Ae/Be stars (HAEBESs) in order to explore the origin of the T ∼ 105 K gas in these stars. The C iv λλ1548, 1550 line luminosities are compared to nonsimultaneous accretion rate estimates for the objects showing C iv emission. We show that the correlation between LC iv and previously established for classical T Tauri stars (CTTSs) seems to extend into the HAEBE mass regime, although the large spread in literature and AV values makes the actual relationship highly uncertain. With the exception of DX Cha, we find no evidence for hot, optically thick winds in our HAEBE sample. All other objects showing clear doublet emission in C iv can be well described by a two-component (i.e., a single component for each doublet member) or four-component (i.e., two components for each doublet member) Gaussian emission line fit. The morphologies and peak-flux velocities of these lines suggest that they are formed in weak, optically thin stellar winds and not in an accretion flow, as is the case for the hot lines observed in CTTSs. The lack of strong outflow signatures and lack of evidence for line formation in accretion flows are consistent with the conclusion presented in our recent optical and He i λ10830 studies that the immediate circumstellar environments of HAEBESs, in general, are not scaled-up analogs of the immediate environments around CTTSs. The conclusions presented here for hot gas lines around HAEBESs should be verified with a larger sample of objects.
A comparative mRNA- and miRNA transcriptomics reveals novel molecular signatures associated with metastatic prostate cancers

Background: Prostate cancer (PC) is a fatally aggressive urogenital cancer killing millions of men, globally. Thus, this study aims to identify key miRNAs, target genes, and drug targets associated with prostate cancer metastasis. Methods: The miRNA and mRNA expression datasets of 148 prostate tissue biopsies (39 tumours and 109 normal tissues), were analysed by differential gene expression analysis, protein interactome mapping, biological pathway analysis, miRNA-mRNA networking, drug target analysis, and survival curve analysis. Results: The dysregulated expression of 53 miRNAs and their 250 target genes involved in Hedgehog, ErbB, and cAMP signalling pathways connected to cell growth, migration, and proliferation of prostate cancer cells was detected. The subsequent miRNA-mRNA network and expression status analysis have helped us in narrowing down their number to 3 hub miRNAs (hsa-miR-455-3p, hsa-miR-548c-3p, and hsa-miR-582-5p) and 9 hub genes (NFIB, DICER1, GSK3B, DCAF7, FGFR1OP, ABHD2, NACC2, NR3C1, and FGF2). Further investigations with different systems biology methods have prioritized NR3C1, ABHD2, and GSK3B as potential genes involved in prostate cancer metastasis owing to their high mutation load and expression status. Interestingly, down regulation of NR3C1 seems to improve the prostate cancer patient survival rate beyond 150 months. The NR3C1, ABHD2, and GSK3B genes are predicted to be targeted by hsa-miR-582-5p, besides some antibodies, PROTACs and inhibitory molecules. Conclusion: This study identified key miRNAs (miR-548c-3p and miR-582-5p) and target genes (NR3C1, ABHD2, and GSK3B) as potential biomarkers for metastatic prostate cancers from large-scale gene expression data using systems biology approaches.
Use of person-centered goals to direct interdisciplinary care for military service members and Veterans with chronic mTBI and co-occurring psychological conditions

Objective To explore the use of person-centered goals (PCGs) to direct interdisciplinary care to support PCG attainment in military service members and Veterans (SM/Vs) with chronic mild traumatic brain injury (mTBI) and co-occurring psychological conditions. Methods A retrospective chart review was completed for 146 United States military SM/Vs reporting chronic symptoms following mTBI and co-occurring psychological conditions who received care in the SHARE Military Initiative intensive outpatient program, a donor-funded program administered by a not-for-profit hospital, between April 1, 2015 and March 31, 2019. PCGs were used to direct care consisting of individual and group-based interventions and therapies delivered by an interdisciplinary, co-located team including behavioral health, case management, neurology or physiatry, nursing, occupational therapy, physical therapy, recreation therapy, speech-language pathology, and transition support. The primary outcome measure was PCG attainment measured via goal attainment scaling. Results Increased PCG attainment was demonstrated at program discharge and throughout the first year following program discharge. Predictors of goal attainment at discharge included longer participation in treatment, greater reduction in depressive symptoms and greater improvement in adjustment at discharge, male gender, and higher cognitive and physical abilities on admission. Conclusions This sample of military SM/Vs with mTBI and co-occurring psychological conditions who received intensive, interdisciplinary, PCG directed care demonstrated increased PCG attainment at program discharge which further increased with transition support over the year post-discharge. Results suggest PGC goal directed care is a feasible, promising methodology of individualizing treatment in this population. This exploratory study lays a foundation for future prospective, controlled, comparative effectiveness research that will further understanding of the effectiveness of intensive, interdisciplinary, PCG directed care.
A practical nomogram based on serum interleukin-6 for the prognosis of liver failure

Background Liver failure (LF) is a serious liver function damage caused by various factors, mainly jaundice, hepatic encephalopathy, coagulation disorders and multiple organ failure, with the clinical characteristic of high short-term mortality. LF is often accompanied by excessive activation of inflammatory factors, and an excessive systemic inflammatory response (i.e., inflammatory storm) is considered to be the trigger of LF. However, a specific prognostic model including inflammatory factors for patients with LF has not been well established. Aim To establish and validate a nomogram for predicting 28-day, 90-day, and 180-day mortality in patients with LF. Methods A total of 423 eligible LF patients were enrolled in this retrospective study. Independent predictors were identified using a multivariate logistic model and then integrated into a nomogram to predict 28-day, 90-day, and 180-day mortality. The concordance index, receiver operating characteristic curves, and calibration plots were used to evaluate the performance of the model. Results Sex, age, total bilirubin, aspartate aminotransferase, international normalized ratio, Child–Pugh score, and serum interleukin-6 were independent risk factors for death at 28, 90, and 180 days in LF patients. The nomogram showed good calibration and discrimination with an area under the receiver operating characteristic curve (AUC) of 0.927. The calibration curve fit as well, indicating that the nomogram had good clinical application value. Conclusion This nomogram model for predicting the 28-day, 90-day, and 180-day mortality of LF patients could help optimize treatment strategies and improve prognosis.
Role of CXCR5+ CD8+ T cells in human immunodeficiency virus-1 infection

Human immunodeficiency virus (HIV) infection can be effectively suppressed by life-long administration of combination antiretroviral therapy (cART). However, the viral rebound can occur upon cART cessation due to the long-term presence of HIV reservoirs, posing a considerable barrier to drug-free viral remission. Memory CD4+ T cell subsets, especially T follicular helper (TFH) cells that reside in B-cell follicles within lymphoid tissues, are regarded as the predominant cellular compartment of the HIV reservoir. Substantial evidence indicates that HIV-specific CD8+ T cell-mediated cellular immunity can sustain long-term disease-free and transmission-free HIV control in elite controllers. However, most HIV cure strategies that rely on expanded HIV-specific CD8+ T cells for virus control are likely to fail due to cellular exhaustion and TFH reservoir-specialized anatomical structures that isolate HIV-specific CD8+ T cell entry into B-cell follicles. Loss of stem-like memory properties is a key feature of exhaustion. Recent studies have found that CXC chemokine receptor type 5 (CXCR5)-expressing HIV-specific CD8+ T cells are memory-like CD8+ T cells that can migrate into B-cell follicles to execute inhibition of viral replication. Furthermore, these unique CD8+ T cells can respond to immune checkpoint blockade (ICB) therapy. In this review, we discuss the functions of these CD8+ T cells as well as the translation of findings into viable HIV treatment and cure strategies.