Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovering genetic linkage between periodontitis and type 1 diabetes: A bioinformatics study

Background: Relationship between periodontitis (PD) and type 1 diabetes (T1D) has been reported, but the detailed pathogenesis requires further elucidation. This study aimed to reveal the genetic linkage between PD and T1D through bioinformatics analysis, thereby providing novel insights into scientific research and clinical treatment of the two diseases. Methods: PD-related datasets (GSE10334, GSE16134, GSE23586) and T1D-related datasets(GSE162689)were downloaded from NCBI Gene Expression Omnibus (GEO). Following batch correction and merging of PD-related datasets as one cohort, differential expression analysis was performed (adjusted p-value <0.05 and ∣log2 fold change| > 0.5), and common differentially expressed genes (DEGs) between PD and T1D were extracted. Functional enrichment analysis was conducted via Metascape website. The protein-protein interaction (PPI) network of common DEGs was generated in The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Hub genes were selected by Cytoscape software and validated by receiver operating characteristic (ROC) curve analysis. Results: 59 common DEGs of PD and T1D were identified. Among these DEGs, 23 genes were commonly upregulated, and 36 genes were commonly downregulated in both PD- and T1D-related cohorts. Functional enrichment analysis indicated that common DEGs were mainly enriched in tube morphogenesis, supramolecular fiber organization, 9 + 0 non-motile cilium, plasma membrane bounded cell projection assembly, glomerulus development, enzyme-linked receptor protein signaling pathway, endochondral bone morphogenesis, positive regulation of kinase activity, cell projection membrane and regulation of lipid metabolic process. After PPI construction and modules selection, 6 hub genes (CD34, EGR1, BBS7, FMOD, IGF2, TXN) were screened out and expected to be critical in linking PD and T1D. ROC analysis showed that the AUC values of hub genes were all greater than 70% in PD-related cohort and greater than 60% in T1D-related datasets. Conclusion: Shared molecular mechanisms between PD and T1D were revealed in this study, and 6 hub genes were identified as potential targets in treating PD and T1D.
Multimorbidity patterns and mortality in older adults: Results from the KORA-Age study

The coexistence of several chronic diseases is very common in older adults, making it crucial to understand multimorbidity (MM) patterns and associated mortality. We aimed to determine the prevalence of MM and common chronic disease combinations, as well as their impact on mortality in men and women aged 65 years and older using the population-based KORA-Age study, based in South of Germany. The chronic disease status of the participants was determined in 2008/9, and mortality status was followed up until 2016. MM was defined as having at least two chronic diseases. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and the 95% confidence intervals (CIs) for associations between MM and all-cause mortality. During the study period 495 men (24.6%) and 368 women (17.4%) died. Although the MM prevalence was almost the same in men (57.7%) and women (60.0%), the overall effect of MM on mortality was higher in men (HR: 1.81, 95% CI: 1.47–2.24) than in women (HR: 1.28, 95% CI: 1.01–1.64; p-value for interaction <0.001). The type of disease included in the MM patterns had a significant impact on mortality risk. For example, when both heart disease and diabetes were included in the combinations of two and three diseases, the mortality risk was highest. The risk of premature death does not only depend on the number of diseases but also on the specific disease combinations. In this study, life expectancy depended strongly on a few diseases, such as diabetes, hypertension, and heart disease.
Planktonic foraminiferal assemblages reflect warming during two recent mid-latitude marine heatwaves

Under future climate scenarios, ocean temperatures that are presently extreme and qualify as marine heatwaves (MHW) are forecasted to increase in frequency and intensity, but little is known about the impact of these events on one of the most common paleoproxies, planktonic foraminifera. Planktonic foraminifera are globally ubiquitous, shelled marine protists. Their abundances and geochemistry vary with ocean conditions and fossil specimens are commonly used to reconstruct ancient ocean conditions. Planktonic foraminiferal assemblages are known to vary globally with sea surface temperature, primary productivity, and other hydrographic conditions, but have not been studied in the context of mid-latitude MHWs. For this study, the community composition and abundance of planktonic foraminifera were quantified for 2010-2019 along the Newport Hydrographic Line, a long-term monitoring transect at 44.6°N in the Northern California Current (NCC). Samples were obtained from archived plankton tows spanning 46 to 370 km offshore during annual autumn (August – October) cruises. Two MHWs impacted the region during this timeframe: the first during 2014-2016 and a second, shorter duration MHW in 2019. During the 2014-2016 MHW, warm water subtropical and tropical foraminifera species were more prevalent than the typical polar, subpolar, and transitional species common to this region. Cold water species were abundant again after the first MHW dissipated in late 2016. During the second, shorter-duration MHW in 2019, the assemblage consisted of a warm water assemblage but did not include tropical species. The foraminiferal assemblage variability correlated with changes in temperature and salinity in the upper 100 meters and was not correlated with distance offshore or upwelling. These results suggest that fossil foraminiferal assemblages from deep sea sediment cores may provide insight into the magnitude and frequency of past MHWs.
Amplified sinus-P-wave analysis predicts outcomes of cryoballoon ablation in patients with persistent and long-standing persistent atrial fibrillation: A multicentre study

Introduction Outcomes of catheter ablation for non-paroxysmal atrial fibrillation (AF) remain suboptimal. Non-invasive stratification of patients based on the presence of atrial cardiomyopathy (ACM) could allow to identify the best responders to pulmonary vein isolation (PVI). Methods Observational multicentre retrospective study in patients undergoing cryoballoon-PVI for non-paroxysmal AF. The duration of amplified P-wave (APW) was measured from a digitally recorded 12-lead electrocardiogram during the procedure. If patients were in AF, direct-current cardioversion was performed to allow APW measurement in sinus rhythm. An APW cut-off of 150 ms was used to identify patients with significant ACM. We assessed freedom from arrhythmia recurrence at long-term follow-up in patients with APW ≥ 150 ms vs. APW < 150 ms. Results We included 295 patients (mean age 62.3 ± 10.6), of whom 193 (65.4%) suffered from persistent AF and the remaining 102 (34.6%) from long-standing persistent AF. One-hundred-forty-two patients (50.2%) experienced arrhythmia recurrence during a mean follow-up of 793 ± 604 days. Patients with APW ≥ 150 ms had a significantly higher recurrence rate post ablation compared to those with APW < 150 ms (57.0% vs. 41.6%; log-rank p < 0.001). On a multivariable Cox-regression analysis, APW≥150 ms was the only independent predictor of arrhythmia recurrence post ablation (HR 2.03 CI95% 1.28–3.21; p = 0.002). Conclusion APW duration predicts arrhythmia recurrence post cryoballoon-PVI in persistent and long-standing persistent AF. An APW cut-off of 150 ms allows to identify patients with significant ACM who have worse outcomes post PVI. Analysis of APW represents an easy, non-invasive and highly reproducible diagnostic tool which allows to identify patients who are the most likely to benefit from PVI-only approach.
How growth mindset influences mathematics achievements: A study of Chinese middle school students

Introduction It has been suggested that students with growth mindsets are more likely to achieve better mathematics learning results than their counterparts with fixed mindsets. However, inconsistent and some even contradictory results have been reported in recent studies which examined the associations between growth mindset and mathematics achievements, suggesting the complexity regarding the effects of growth mindset on academic achievements. Methods This study aims to examine students' growth mindsets, failure attributions, intrinsic motivation, mathematics self-efficacy, mathematics anxiety and mathematics achievements in one model to capture the sophisticated functioning processes of growth mindset. A total number of 266 middle school students in China participated in this study. Students' mindset and related variables (i.e.,motivations to learn mathematics, attributions of failure in mathematics, mathematics anxiety, mathematics self-efficacy) were measured at year 7, the first year of junior middle school in China. These students' mathematics learning outcomes were tracked from year 7 to year 9, the end of junior middle school. Structural equation modeling (SEM) was used to investigate the relations among students' growth mindsets, failure attributions, intrinsic motivation, mathematics self-efficacy, mathematics anxiety and mathematics achievements. Results The results show that: (1) growth mindset doesn't directly predict mathematics achievements; (2) growth mindset indirectly influences mathematics achievements through intrinsic motivation; (3) failure attributions and mathematics self-efficacy sequentially mediate the association between growth mindset mathematics achievements; (4) failure attributions and mathematics anxiety sequentially mediate the relationship between growth mindset mathematics achievements. Discussion The results of this study contribute a better understanding about how growth mindsets make impacts on middle school students' mathematics achievements. These findings have important implications for mathematics education in that we could not simply cultivate students' growth mindset in schools with expectations of higher mathematics learning outcomes. Instead, along with the growth mindset intervention, it is fundamental to make interventions on students' intrinsic motivation, failure attribution, mathematics self-efficacy, and mathematics anxiety in mathematics teaching and learning.
Plant-made vaccines against viral diseases in humans and farm animals

Plants provide not only food and feed, but also herbal medicines and various raw materials for industry. Moreover, plants can be green factories producing high value bioproducts such as biopharmaceuticals and vaccines. Advantages of plant-based production platforms include easy scale-up, cost effectiveness, and high safety as plants are not hosts for human and animal pathogens. Plant cells perform many post-translational modifications that are present in humans and animals and can be essential for biological activity of produced recombinant proteins. Stimulated by progress in plant transformation technologies, substantial efforts have been made in both the public and the private sectors to develop plant-based vaccine production platforms. Recent promising examples include plant-made vaccines against COVID-19 and Ebola. The COVIFENZ® COVID-19 vaccine produced in Nicotiana benthamiana has been approved in Canada, and several plant-made influenza vaccines have undergone clinical trials. In this review, we discuss the status of vaccine production in plants and the state of the art in downstream processing according to good manufacturing practice (GMP). We discuss different production approaches, including stable transgenic plants and transient expression technologies, and review selected applications in the area of human and veterinary vaccines. We also highlight specific challenges associated with viral vaccine production for different target organisms, including lower vertebrates (e.g., farmed fish), and discuss future perspectives for the field.
Transcriptional regulation of innate lymphoid cells and T cells by aryl hydrocarbon receptor

The aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor and facilitates immune cell environmental sensing through its activation by cellular, dietary, and microbial metabolites, as well as environmental toxins. Although expressed in various cell types, Ahr in innate lymphoid cells (ILCs) and their adaptive T cell counterparts regulates essential aspects of their development and function. As opposed to T cells, ILCs exclusively rely on germ-line encoded receptors for activation, but often share expression of core transcription factors and produce shared effector molecules with their T cell counterparts. As such, core modules of transcriptional regulation are both shared and diverge between ILCs and T cells. In this review, we highlight the most recent findings regarding Ahr’s transcriptional regulation of both ILCs and T cells. Furthermore, we focus on insights elucidating the shared and distinct mechanisms by which Ahr regulates both innate and adaptive lymphocytes.
Pomegranate peel extract protects against the development of diabetic cardiomyopathy in rats by inhibiting pyroptosis and downregulating LncRNA-MALAT1

Background: Pyroptosis is an inflammatory programmed cell death accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. Pyroptosis is closely linked to the development of diabetic cardiomyopathy (DC). Pomegranate peel extract (PPE) exhibits a cardioprotective effect due to its antioxidant and anti-inflammatory properties. This study aimed to investigate the underlying mechanisms of the protective effect of PPE on the myocardium in a rat model of DC and determine the underlying molecular mechanism. Methods: Type 1 diabetes (T1DM) was induced in rats by intraperitoneal injection of streptozotocin. The rats in the treated groups received (150 mg/kg) PPE orally and daily for 8 weeks. The effects on the survival rate, lipid profile, serum cardiac troponin-1, lipid peroxidation, and tissue fibrosis were assessed. Additionally, the expression of pyroptosis-related genes (NLRP3 and caspase-1) and lncRNA-MALAT1 in the heart tissue was determined. The PPE was analyzed using UPLC-MS/MS and NMR for characterizing the phytochemical content. Results: Prophylactic treatment with PPE significantly ameliorated cardiac hypertrophy in the diabetic rats and increased the survival rate. Moreover, prophylactic treatment with PPE in the diabetic rats significantly improved the lipid profile, decreased serum cardiac troponin-1, and decreased lipid peroxidation in the myocardial tissue. Histopathological examination of the cardiac tissues showed a marked reduction in fibrosis (decrease in collagen volume and number of TGF-β-positive cells) and preservation of normal myocardial structures in the diabetic rats treated with PPE. There was a significant decrease in the expression of pyroptosis-related genes (NLRP3 and caspase-1) and lncRNA-MALAT1 in the heart tissue of the diabetic rats treated with PPE. In addition, the concentration of IL-1β and caspase-1 significantly decreased in the heart tissue of the same group. The protective effect of PPE on diabetic cardiomyopathy could be due to the inhibition of pyroptosis and downregulation of lncRNA-MALAT1. The phytochemical analysis of the PPE indicated that the major compounds were hexahydroxydiphenic acid glucoside, caffeoylquinic acid, gluconic acid, citric acid, gallic acid, and punicalagin. Conclusion: PPE exhibited a cardioprotective potential in diabetic rats due to its unique antioxidant, anti-inflammatory, and antifibrotic properties and its ability to improve the lipid profile. The protective effect of PPE on DC could be due to the inhibition of the NLRP3/caspase-1/IL-1β signaling pathway and downregulation of lncRNA-MALAT1. PPE could be a promising therapy to protect against the development of DC, but further clinical studies are recommended.
Population pharmacokinetics and model-based dosing evaluation of bedaquiline in multidrug-resistant tuberculosis patients

Aims: Bedaquiline is now recommended to all patients in the treatment of multidrug-resistant tuberculosis (MDR-TB) using standard dosing regimens. As the ability to measure blood drug concentrations is very limited, little is known about drug exposure and treatment outcome. Thus, this study aimed to model the population pharmacokinetics as well as to evaluate the currently recommended dosage. Methodology: A bedaquiline population pharmacokinetic (PK) model was developed based on samples collected from the development cohort before and 1, 2, 3, 4, 5, 6, 8, 12, 18, and 24 h after drug intake on week 2 and week 4 of treatment. In a prospective validation cohort of patients with MDR-TB, treated with bedaquiline-containing standardized regimen, drug exposure was assessed using the developed population PK model and thresholds were identified by relating to 2-month and 6-month sputum culture conversion and final treatment outcome using classification and regression tree analysis. In an exploratory analysis by the probability of target attainment (PTA) analysis, we evaluated the recommended dosage at different MIC levels by Middlebrook 7H11 agar dilution (7H11). Results: Bedaquiline pharmacokinetic data from 55 patients with MDR-TB were best described by a three-compartment model with dual zero-order input. Body weight was a covariate of the clearance and the central volume of distribution, albumin was a covariate of the clearance. In the validation cohort, we enrolled 159 patients with MDR-TB. The 7H11 MIC mode (range) of bedaquiline was 0.06 mg (0.008–0.25 mg/L). The study participants with AUC0-24h/MIC above 175.5 had a higher probability of culture conversion after 2-month treatment (adjusted relative risk, aRR:16.4; 95%CI: 5.3–50.4). Similarly, those with AUC0-24h/MIC above 118.2 had a higher probability of culture conversion after 6-month treatment (aRR:20.1; 95%CI: 2.9–139.4), and those with AUC0-24h/MIC above 74.6 had a higher probability of successful treatment outcome (aRR:9.7; 95%CI: 1.5–64.8). Based on the identified thresholds, simulations showed that the WHO recommended dosage (400 mg once daily for 14 days followed by 200 mg thrice weekly) resulted in PTA >90% for the majority of isolates (94%; MICs ≤0.125 mg/L). Conclusion: We established a population PK model for bedaquiline in patients with MDR-TB in China. Based on the thresholds and MIC distribution derived in a clinical study, the recommended dosage of bedaquiline is sufficient for the treatment of MDR-TB.
Synergistic structural and functional alterations in the medial prefrontal cortex of patients with high-grade gliomas infiltrating the thalamus and the basal ganglia

Background High-grade gliomas (HGGs) are characterized by a high degree of tissue invasion and uncontrolled cell proliferation, inevitably damaging the thalamus and the basal ganglia. The thalamus exhibits a high level of structural and functional connectivity with the default mode network (DMN). The present study investigated the structural and functional compensation within the DMN in HGGs invading the thalamus along with the basal ganglia (HITBG). Methods A total of 32 and 22 healthy controls were enrolled, and their demographics and neurocognition (digit span test, DST) were assessed. Of the 32 patients, 18 patients were involved only on the left side, while 15 of them were involved on the right side. This study assessed the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), gray matter (GM) volume, and functional connectivity (FC) within the DMN and compared these measures between patients with left and right HITBG and healthy controls (HCs). Result The medial prefrontal cortex (mPFC) region existed in synchrony with the significant increase in ALFF and GM volume in patients with left and right HITBG compared with HCs. In addition, patients with left HITBG exhibited elevated ReHo and GM precuneus volumes, which did not overlap with the findings in patients with right HITBG. The patients with left and right HITBG showed decreased GM volume in the contralateral hippocampus without any functional variation. However, no significant difference in FC values was observed in the regions within the DMN. Additionally, the DST scores were significantly lower in patients with HITBG, but there was no significant correlation with functional or GM volume measurements. Conclusion The observed pattern of synchrony between structure and function was present in the neuroplasticity of the mPFC and the precuneus. However, patients with HITBG may have a limited capacity to affect the connectivity within the regions of the DMN. Furthermore, the contralateral hippocampus in patients with HITBG exhibited atrophy. Thus, preventing damage to these regions may potentially delay the progression of neurological function impairment in patients with HGG.
The impact of adolescent achievement goal orientation on learning anxiety: The mediation effect of peer interaction

Learning anxiety is one of the most critical emotional disturbances, which also has a high incidence rate in adolescents. Peer interaction is critical and unique for adolescents. Although previous studies have found that achievement goal orientation has an important role in the development of learning anxiety, its mechanism has not been clarified. This study surveyed 470 adolescents (191 middle school students and 279 high school students; 211 boys) and established a structural equation model to explore the mediating role of peer interaction in the influence of achievement goal orientation on learning anxiety. Results showed that (1) there were significant gender differences in mastery-avoidance goal orientation, peer interaction, and learning anxiety, and there were grade differences in performance-approach goal and performance-avoidance goal orientations; (2) mastery-approach, mastery-avoidance, and performance-avoidance goal orientations directly predicted learning anxiety; and (3) social anxiety in peer interactions had a mediating effect on the influence of mastery-approach, mastery-avoidance, and performance-avoidance goal orientations on learning anxiety. The findings extend theoretical considerations by teasing out the process of peer interaction affecting the relationship between achievement goal orientation and learning anxiety. Additionally, the results have practical implications for the effective use of peer interaction to reduce learning anxiety.
Understanding the associations between the number of close friends and life satisfaction: Considering age differences

Life satisfaction refers to one's subjective evaluation of life, which is the cognitive aspect of subjective well-being. Understanding factors that contribute to life satisfaction has important implications as higher life satisfaction is closely associated with better physical, psychological, and behavioral health outcomes. Close friendship serves as a valuable source of social support across life spans. Although there are some studies regarding the associations between friendship and well-being, much less is known regarding the relationships between the number of close friends and life satisfaction and how this association varies with age. By analyzing data from 29,785 participants with an age range of 16–101 years old from the Understanding Society, the current study found that there is a significant interaction effect of age with the number of close friends (b = −0.003, p < 0.01, 95% C.I. [−0.004, −0.001]) after controlling for demographic covariates. Simple slope regressions showed that the positive association between the number of close friends and life satisfaction is the strongest in young people (b = 0.018, p < 0.001, 95% C.I. [0.012, 0.024]), and less strong in middle-aged (b = 0.008, p < 0.001, 95% C.I. [0.003, 0.013]), and the weakest in older adults (b = 0.004, p < 0.01, 95% C.I. [0.002, 0.007]).