Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Chitchatting: Exploring the Role of Exosomes as Cardiovascular Risk Factors

Exosomes are small bi-lipid membranous vesicles (30–150 nm) containing different biological material such as proteins, lipids and nucleic acid. These small vesicles, inducing a cell to cell signaling pathway, are able to mediate multidirectional crosstalk to maintain homeostasis or modulate disease processes. With their various contents, exosomes sort and transfer specific information from their origin to a recipient cell, from a tissue or organ in the close proximity or at distance, generating an intra-inter tissue or organ communication. In the last decade exosomes have been identified in multiple organs and fluids under different pathological conditions. In particular, while the content and the abundance of exosome is now a diagnostic marker for cardiovascular diseases, their role in context-specific physiological and pathophysiological conditions in the cardiovascular system remains largely unknown. We summarize here the current knowledge on the role of exosomes as mediators of cardiovascular diseases in several pathophysiological conditions such as atherosclerosis and diabetes. In addition, we describe evidence of intercellular connection among multiple cell type (cardiac, vasculature, immune cells) as well as the challenge of their in vivo analysis.
Total Brain Volumetric Measures and Schizophrenia Risk: A Two-Sample Mendelian Randomization Study

Schizophrenia (SCZ) is an idiopathic psychiatric disorder with a heritable component and a substantial public health impact. Although abnormalities in total brain volumetric measures (TBVMs) have been found in patients with SCZ, it is still unknown whether these abnormalities have a causal effect on the risk of SCZ. Here, we performed a Mendelian randomization (MR) study to investigate the possible causal associations between each TBVM and SCZ risk. Specifically, genome-wide association study (GWAS) summary statistics of total gray matter volume, total white matter volume, total cerebrospinal fluid volume, and total brain volume were obtained from the United Kingdom Biobank database (33,224 individuals), and SCZ GWAS summary statistics were provided by the Psychiatric Genomics Consortium (150,064 individuals). The main MR analysis was conducted using the inverse variance weighted method, and other MR methods, including MR-Egger, weighted median, simple mode, and weighted mode methods, were performed to assess the robustness of our findings. For pleiotropy analysis, we employed three approaches: MR-Egger intercept, MR-PRESSO, and heterogeneity tests. No TBVM was causally associated with SCZ risk according to the MR results, and no significant pleiotropy or heterogeneity was found for instrumental variables. Taken together, this study suggested that alterations in TBVMs were not causally associated with the risk of SCZ.
What Is Targeted When We Train Working Memory? Evidence From a Meta-Analysis of the Neural Correlates of Working Memory Training Using Activation Likelihood Estimation

Working memory (WM) is the system responsible for maintaining and manipulating information, in the face of ongoing distraction. In turn, WM span is perceived to be an individual-differences construct reflecting the limited capacity of this system. Recently, however, there has been some evidence to suggest that WM capacity can increase through training, raising the possibility that training can functionally alter the neural structures supporting WM. To address the hypothesis that the neural substrates underlying WM are targeted by training, we conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of WM training using Activation Likelihood Estimation (ALE). Our results demonstrate that WM training is associated exclusively with decreases in blood oxygenation level-dependent (BOLD) responses in clusters within the fronto-parietal system that underlie WM, including the bilateral inferior parietal lobule (BA 39/40), middle (BA 9) and superior (BA 6) frontal gyri, and medial frontal gyrus bordering on the cingulate gyrus (BA 8/32). We discuss the various psychological and physiological mechanisms that could be responsible for the observed reductions in the BOLD signal in relation to WM training, and consider their implications for the construct of WM span as a limited resource.
Juglone and KPT6566 Suppress the Tumorigenic Potential of CD44+CD133+ Tumor-Initiating Caco-2 Cells In Vitro and In Vivo

Pin1, a cis/trans isomerase of peptidyl-prolyl peptide bonds, plays a crucial role in the pathogenesis of many human cancers. Although chemical inhibitors of Pin1 show potent antitumor therapeutic properties against various cancers, their effect on colorectal cancer, especially colorectal tumor-initiating cells, remains unknown. Here, we investigated the effect of Juglone and KPT6566 on Caco-2 cells and tumor-initiating Caco-2 cells. Juglone and KPT6566 inhibited cell growth and colony formation, and induced apoptosis of Caco-2 cells. We also found that Juglone and KPT6566 downregulated expression of G1-phase-specific cyclins and cyclin-dependent kinases in a time-dependent manner, consistent with suppression of Caco-2 cell proliferation and colony formation. Although tumor-initiating cells are thought to be responsible for resistance to traditional chemotherapeutic drugs, our experiments demonstrate that Juglone or KPT6566 kill both tumor-initiating and non-tumor-initiating Caco-2 cells with equal or similar efficacy. Finally, when CD44+CD133+ tumor-initiating Caco-2 cells were injected into NSG mice, Juglone or KPT6566 led to a meaningful reduction in tumor volume and mass compared with tumors isolated from mice that received control treatment. Overall, these results indicate that chemical Pin1 inhibitors may be a valuable therapeutic option against colorectal tumor-initiating cancer cells.
Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease

Background and objective This pilot study aimed to identify potential blood DNA methylation (BDM) biomarker genes for the diagnosis of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods We included a total of 16 NAFLD patients with significant (SLF, liver fibrosis stage ≥ 2) and 16 patients with non-significant liver fibrosis (NSLF, fibrosis stages 0–1). The association between BDM and liver fibrosis was analyzed. Genes were selected based on a stepwise-filtering with CpG islands containing significant differentially methylated probes. Results The two groups of patients were distinguishable through both t-distributed stochastic neighbor embedding (t-SNE) analysis and unsupervised hierarchical clustering analysis based on their BDM status. BDM levels were significantly higher in the NSLF group than in the SLF group. The methylation levels in the island and shelf regions were also significantly higher in the NSLF group, as well as the methylation levels in the first exon, 3′-untranslated region, body, ExonBnd, non-intergenic region, transcription start site (TSS)1500, and TSS200 regions (all p < 0.05). BDM status was associated with greater histological liver fibrosis, but not with age, sex, or other histological features of NAFLD (p < 0.05). The methylation levels of the hypomethylated CpG island region of CISTR, IFT140, and RGS14 genes were increased in the NSLF group compared to the SLF group (all p < 0.05). Conclusion BDM may stratify NAFLD patients with significant and non-significant liver fibrosis. The CISTR, IFT140, and RGS14 genes are potential novel candidate BDM biomarkers for liver fibrosis and these pilot data suggest further work on BDM biomarkers is warranted.
Perspective: Utilizing High Amylose Wheat Flour to Increase Dietary Fiber Intake of Children and Adolescents: A Health by Stealth Approach

Children and adolescents have consistently failed to meet recommended levels of dietary fiber consumption, thus making fiber a nutrient of concern. The importance of adequate dietary fiber intake to attain a healthy diet necessitates the identification of fiber-rich and readily consumed food sources by youth. Grain-based foods derived from whole grains represent a strategic initiative to increase dietary fiber consumption and is consistent with the American diet pattern. Increased intake of foods made from whole grains have been positively associated with improved health outcomes but are also less preferred among youth compared to refined grain products, which make up the majority of their carbohydrate intake. Advances in the commercialization and availability of high amylose wheat flour, a source of resistant starch fiber, provides an opportunity to remedy the suggested acceptability issues of whole grain products indicative of sensory factors, without compromising the amount of fiber ingested. Resistant starch fiber consumption has been associated with health benefits including improved blood sugar management, improved markers of digestive and gut health, increased satiety, and a reduced inflammatory response among adults. The limited studies that indicate fiber's direct benefit among youth are largely observational, thereby necessitating the need for more controlled trials for these age groups. Replacing traditional refined wheat flour with refined high amylose wheat flour has the unique ability to increase dietary fiber consumption without compromising desired sensory and finished product characteristics and thus can help increase dietary fiber consumption in children and adolescents who struggle to meet adequate intakes of fiber.
Medicinal Earthworm: Speciation and Bioaccessibility of Arsenic and Its Potential Health Risks

Arsenic in environmental health has caused public concerns all over the world. However, high levels of arsenic residues in medicinal animals have not received enough attention. Medicinal earthworms are consumed widely in China, but its arsenic potential health risks to humans are unknown. This work investigated the total concentration, bioaccessibility, and speciation of arsenic in earthworms by ICP-MS and HPLC-ICP-MS to evaluate its potential health risks to humans. Arsenic was found in all earthworms at concentrations ranging from 0.4 to 53.6 mg kg−1. The bioaccessibility of arsenic (bAs) varied significantly and ranged from 12.1 to 69.1%, with inorganic arsenic (iAs, including As(III) and As(V)) as the predominant species. Furthermore, a small amount of arsenobetaine (AB) was found. The estimated daily intake dose (EDI), hazard quotient (HQ), and carcinogenic risk (CR) of arsenic in most of the samples exceeded the safe threshold level. Results from this study indicated that the potential health risks by the consumption of earthworms may not be negligible. Herein, recommendations for the use of earthworms and regulatory recommendations for arsenic limit standards were proposed. This study reminds us that more control and monitoring of arsenic in medicinal animals should be carried out.
Quantitative Assessment of Portal Hypertension by Two-Dimensional Shear Wave Elastography in Rat Models of Nonalcoholic Fatty Liver Disease: Comparison With Four Composite Scores

Background Measurement of hepatic venous pressure gradients is the gold standard for assessing portal hypertension (PH) but is invasive with potential complications. We aimed to assess the performance in liver and spleen stiffness measurement (LSM and SSM, respectively) by two-dimensional shear wave elastography (2D-SWE) and composite scores including liver stiffness-spleen diameter to platelet ratio score (LSPS), platelet (PLT) count/spleen diameter ratio (PSR), aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), and AST-to-PLT ratio index (APRI) for diagnosing PH in nonalcoholic fatty liver disease (NAFLD) rat models. Methods Animal models with PH in NAFLD were established in 65 rats, which then underwent 2D-SWE measurements. Morphological and biological parameters were collected for calculation of four composite scores. Correlations of noninvasive methods with portal venous pressure were evaluated by Spearman correlation analysis. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of noninvasive methods in predicting PH. Results LSM and SSM were significantly associated with portal venous pressure (r = 0.636 and 0.602, respectively; all P < 0.001). The AUCs of LSM and SSM in the diagnosis of PH were 0.906 (95% confidence interval [CI]:0.841–0.97) and 0.87 (95% CI:0.776–0.964), respectively, and were significantly higher than those in composite scores. The AUCs for LSPS, PSR, AAR, and APRI were 0.793, 0.52, 0.668, and 0.533, respectively, for diagnosing PH. The AUCs of the combined models of LSM and SSM, LSM and PLT, SSM and PLT, and LSM, SSM and PLT were 0.923, 0.913, 0.872, and 0.923, respectively. The four combined models showed no statistical differences compared to LSM and SSM in evaluating PH (all P > 0.05). Conclusions LSM and SSM by 2D-SWE can be used as promising noninvasive parameters for diagnosing PH in NAFLD and have higher accuracy than composite scores. The combined models, compared to LSM and SSM, did not significantly improve the performance in diagnosing PH.
Exploration and Petrogenesis of Corundum-Bearing Pegmatites: A Case Study in Migif-Hafafit Area, Egypt

A net of pegmatite veins crosscut gneiss and dismembered ophiolitic ultramafic rocks are abundant in the Migif-Hafafit culmination area, South Eastern Desert, Egypt. Some of these pegmatites are corundum-bearing. Corundum-bearing pegmatites are studied in eight localities around the Migif-Hafafit complex. The present study aims to integrate field investigation, whole rock and corundum chemistry, remote sensing studies, and the conventional methods to detect the corundum-bearing pegmatites, which led to finding out the genesis of the corundum mineralization. In addition, the tectonic regime has been detected using bulk rock geochemistry. False-color composite (FCCs), band ratio (BR), principal component analysis (PCA), minimum noise fraction (MNF), decorrelation stretch (DS), and the constrained energy minimization (CEM) image processing algorithms were proposed and applied on Landsat-8 OLI, and Sentinel-2A data to discriminate the exposed lithological units and to detect the corundum-bearing pegmatites in the study area. These detected pegmatites are structurally controlled following the NW-SE direction. The ultramafic rocks are the host of six areas and the gneisses are the host rocks of the two others. Gneisses and pegmatites are characterized by a steep slope of LREEs relative to HREEs with week Eu negative anomaly. The studied pegmatites have both plumasite and marundite. On the other hand, the studied corundum has Al2O3 content up to 99.72 wt% in pegmatite-gneiss and up to 100 wt. % in pegmatite-ultramafics. Corundum is ascribed to metamorphic/metasomatic type according to its chromosphere. Desilication in pegmatites led to the excess of alumina content in the residual melt producing corundum mineralization.
Numerical Study on the Improvement of Oil Return Structure in Aero-Engine Bearing Chambers

Abstract Numerical study has been carried out to improve the unreasonable oil film accumulation and oil return effect of the bearing chamber. Ramp sump and eccentricity sump offtake structures are designed and improved, and oil-gas two-phase flow calculation model based on CLSVOF (coupled level set and volume of fluid) method is proposed. Based on the grid-independent analysis and verifying the rationality of numerical data, oil-gas movement mechanism and oil return characteristics for different scavenge offtakes are calculated and analyzed. Results show that both the ramp sump and eccentricity sump offtake structures have favorable effects on improving the local oil distribution such as recirculation and stripping, etc. at low rotation speeds and alleviating the rapid decline of scavenge efficiency at high rotation speeds. Meanwhile, the air shear force is the main reason for the rapid decline of scavenge efficiency, while the design of oil return sump makes for the oil discharge from the scavenge offtake, and the deeper the sump depth is, the better.
Sputum Bacterial Metacommunities in Distinguishing Heterogeneity in Respiratory Health and Disease

Background and Objective Cluster-based analysis, or community typing, has been attempted as a method for studying the human microbiome in various body niches with the aim of reducing variations in the bacterial composition and linking the defined communities to host health and disease. In this study, we have presented the bacterial subcommunities in the healthy and the diseased population cohorts and have assessed whether these subcommunities can distinguish different host health conditions. Methods We performed community typing analysis on the sputum microbiome dataset obtained from a healthy Korean twin-family cohort (n = 202) and an external chronic obstructive pulmonary disease (COPD) cohort (n = 324) and implemented a networks analysis to investigate the associations of bacterial metacommunities with host health parameters and microbial interactions in disease. Results The analysis of the sputum microbiome of a healthy Korean cohort revealed high levels of interindividual variation, which was driven by two dominant bacteria: Neisseria and Prevotella. Community typing of the cohort samples identified three metacommunities, namely, Neisseria 1 (N1), Neisseria 2 (N2), and Prevotella (P), each of which showed different functional potential and links to host traits (e.g., triglyceride levels, waist circumference, and levels of high-sensitivity C-reactive protein). In particular, the Prevotella-dominant metacommunity showed a low-community diversity, which implies an adverse health association. Network analysis of the healthy twin cohort illustrated co-occurrence of Prevotella with pathogenic anaerobic bacteria; this bacterial cluster was negatively associated with high-density lipoproteins but positively correlated with waist circumference, blood pressure, and pack-years. Community typing of the external COPD cohort identified three sub-metacommunities: one exclusively comprising healthy subjects (HSs) and the other two (CS1 and CS2) comprising patients. The two COPD metacommunities, CS1 and CS2, showed different abundances of specific pathogens, such as Serratia and Moraxella, as well as differing functional potential and community diversity. Network analysis of the COPD cohort showed enhanced bacterial coexclusions in the CS metacommunities when compared with HS metacommunity. Conclusion Overall, our findings point to a potential association between pulmonary Prevotella and host health and disease, making it possible to implement community typing for the diagnosis of heterogenic respiratory disease.
Correlation Between Immune Cell Infiltration and PD-L1 Expression and Immune-Related lncRNA Determination in Triple-Negative Breast Cancer

As a key element of the tumor microenvironment (TME), immune cell infiltration (ICI) is a frequently observed histologic finding in people with triple-negative breast cancer (TNBC), and it is linked to immunotherapy sensitivity. Nonetheless, the ICI in TNBC, to the best of our knowledge, has not been comprehensively characterized. In our current work, computational algorithms based on biological data from next-generation sequencing were employed to characterize ICI in a large cohort of TNBC patients. We defined various ICI patterns by unsupervised clustering and constructed the ICI scores using the principal component analysis (PCA). We observed patients with different clustering patterns had distinct ICI profiles and different signatures of differentially expressed genes. Patients with a high ICI score tended to have an increased PD-L1 expression and improved outcomes, and these patients were associated with decreased tumor mutational burden (TMB). Interestingly, it was showed that patients with high TMB exhibited an ameliorated overall survival (OS) than patients with low TMB. Furthermore, TMB scores only affected the prognosis of TNBC patients in the low-ICI score group but not in the high group. Finally, we identified a new immune-related lncRNA (irlncRNA) signature and established a risk model for the TNBC prognosis prediction. In addition, the high-risk group was related to poor prognosis, a high infiltration level of plasma B cells, monocytes, M2 macrophages, and neutrophils and a low PD-L1 expression. Therefore, the characterization and systematic evaluation of ICI patterns might potentially predict the prognosis and immunotherapy response in TNBC patients.
Applications of Non-Coding RNAs in Patients With Retinoblastoma

Retinoblastoma (RB) is the most common primary intraocular malignancy in childhood. In the carcinogenic process of neoplasms such as RB, the role of non-coding RNAs (ncRNAs) has been widely demonstrated recently. In this review, we aim to provide a clinical overview of the current knowledge regarding ncRNAs in relation to RB. Although ncRNAs are now considered as potential diagnostic biomarkers, prognostic factors, and therapeutic targets, further studies will facilitate enhanced understanding of ncRNAs in RB physiopathology and define the roles ncRNAs can play in clinical practice.
Cortical and Subcortical Structural Abnormalities in Patients With Idiopathic Cervical and Generalized Dystonia

Objectives In this study, we sought to investigate structural imaging alterations of patients with idiopathic dystonia at the cortical and subcortical levels. The common and specific changes in two subtypes of dystonia, cervical dystonia (CD) and generalized dystonia (GD), were intended to be explored. Additionally, we sought to identify the morphometric measurements which might be related to patients' clinical characteristics, thus providing more clues of specific brain regions involved in the mechanism of idiopathic dystonia. Methods 3D T1-weighted MRI scans were acquired from 56 patients with idiopathic dystonia and 30 healthy controls (HC). Patients were classified as CD or GD, according to the distinct symptom distributions. Cortical thickness (CT) of 30 CD and 26 GD were estimated and compared to HCs using Computational Anatomy Toolbox (CAT12), while volumes of subcortical structures and their shape alterations (29 CD, 25 GD, and 27 HCs) were analyzed via FSL software. Further, we applied correlation analyses between the above imaging measurements with significant differences and patients' clinical characteristics. Results The results of comparisons between the two patient groups and HCs were highly consistent, demonstrating increased CT of bilateral postcentral, superiorparietal, superiorfrontal/rostralmiddlefrontal, occipital gyrus, etc., and decreased CT of bilateral cingulate, insula, entorhinal, and fusiform gyrus (PFWE < 0.005 at the cluster level). In CD, trends of negative correlations were found between disease severity and CT alterations mostly located in pre/postcentral, rostralmiddlefrontal, superiorparietal, and supramarginal regions. Besides, volumes of bilateral putamen, caudate, and thalamus were significantly reduced in both patient groups, while pallidum volume reduction was also presented in GD compared to HCs. Caudate volume reduction had a trend of correlation to increasing disease severity in GD. Last, shape analysis directly demonstrated regional surface alterations in bilateral thalamus and caudate, where the atrophy located in the head of caudate had a trend of correlation to earlier ages of onset in GD. Conclusions Our study demonstrates wide-spread morphometric changes of CT, subcortical volumes, and shapes in idiopathic dystonia. CD and GD presented similar patterns of morphometric abnormalities, indicating shared underlying mechanisms in two different disease forms. Especially, the clinical associations of CT of multiple brain regions with disease severity, and altered volume/shape of caudate with disease severity/age of onset separately in CD and GD might serve as potential biomarkers for further disease exploration.