Miracle-dz/UniFAR-FTUs huggingface dataset:
The influence of 17q21.31 and APOE genetic ancestry on neurodegenerative disease risk

Advances in genomic research over the last two decades have greatly enhanced our knowledge concerning the genetic landscape and pathophysiological processes involved in multiple neurodegenerative diseases. However, current insights arise almost exclusively from studies on individuals of European ancestry. Despite this, studies have revealed that genetic variation differentially impacts risk for, and clinical presentation of neurodegenerative disease in non-European populations, conveying the importance of ancestry in predicting disease risk and understanding the biological mechanisms contributing to neurodegeneration. We review the genetic influence of two important disease-associated loci, 17q21.31 (the “MAPT locus”) and APOE, to neurodegenerative disease risk in non-European populations, touching on global population differences and evolutionary genetics by ancestry that may underlie some of these differences. We conclude there is a need to increase representation of non-European ancestry individuals in genome-wide association studies (GWAS) and biomarker analyses in order to help resolve existing disparities in understanding risk for, diagnosis of, and treatment for neurodegenerative diseases in diverse populations.
Rhizosphere inoculation of Nicotiana benthamiana with Trichoderma harzianum TRA1-16 in controlled environment agriculture: Effects of varying light intensities on the mutualism-parasitism interaction

Trichoderma spp. , a genus of fast-growing and highly adaptable fungi that form symbiotic relationships with plant roots, rendering them ideal for practical use in controlled environment agriculture. Herein, this paper aims to understand how the Nicotiana benthamiana with inoculation of Trichoderma harzianum strain TRA1-16 responds to light intensity variation. Pot experiments were conducted under low and high light intensities (50 and 150 μmol·m-2·s-1, respectively) and microbial treatments. Plant growth, physio-biochemical attributes, activities of antioxidant enzymes, and phytohormones regulation were investigated. The results showed that for non-inoculated plants, the reduction in light intensity inhibited plant growth, nitrogen (N) and phosphorus (P) uptake, chlorophyll a/b, and carotenoid content. Trichoderma inoculation resulted in 1.17 to 1.51 times higher concentrations of available N and P in the soil than the non-inoculated group, with higher concentrations at high light intensity. Plant height, dry weight, nutrient uptake, and antioxidant activity were significantly increased after inoculation (p<0.05). However, the growth-promoting effect was less effective under low light conditions, with lower plant height and P content in plants. We suggested that when the light was attenuated, the mutualism of the Trichoderma turned into parasitism, slowing the growth of the host plant. The application of fungal inoculation techniques for plant growth promotion required coordination with appropriate light complementation. The mechanisms of coordination and interaction were proposed to be incorporated into the biological market theory.
SLC25A25-AS1 over-expression could be predicted the dismal prognosis and was related to the immune microenvironment in prostate cancer

It has been established that long-chain coding RNA (lncRNA) SLC25A25-AS1 is associated with cancer progression. However, the roles and mechanisms of SLC25A25-AS1 in prostate cancer (PC) have not been reported in the literature. The present study explored the relationship between SLC25A25-AS1 expression and PC progression via comprehensive analysis. The pan-cancer expression of SLC25A25-AS1 was identified using data from The Cancer Genome Atlas (TCGA) database and tissue specimens from our hospital. The expression levels of SLC25A25-AS1 in various subgroups based on the clinical features were identified. The prognostic value of SLC25A25-AS1 and SLC25A25-AS1 co-expressed lncRNAs in PC patients was assessed by survival analysis and ROC analysis, and prognosis-related risk models of SLC25A25-AS1 were constructed. The relationship between SLC25A25-AS1 and the PC immune microenvironment was investigated using correlation analysis. SLC25A25-AS1 expression in PC was significantly increased and correlated with the T stage, clinical stage, Gleason score (GS), and dismal prognosis. SLC25A25-AS1 overexpression exhibited good performance in evaluating the prognosis of PC patients. The area under the curves (AUCs) of the 1-, 3-, and 5-year overall survival (OS) for SLC25A25-AS1 was 1, 0.876, and 0.749. Moreover, the AUCs for the 1-, 3-, and 5-year progress free interval (PFI) for SLC25A25-AS1 were 0.731, 0.701, and 0.718. SLC25A25-AS1 overexpression correlated with the infiltration of CD8 T cells, interstitial dendritic cells (IDC), macrophages and other cells. AC020558.2, ZNF32-AS2, AP4B1-AS1, AL355488.1, AC109460.3, SNHG1, C3orf35, LMNTD2-AS1, and AL365330.1 were significantly associated with SLC25A25-AS1 expression, and short OS and PFI in PC patients. The risk models of the SLC25A25-AS1-related lncRNAs were associated with a dismal prognosis in PC. Overall, SLC25A25-AS1 expression was increased in PC and related to the prognosis and PC immune microenvironment. The risk model of SLC25A25-AS1 have huge prospect for application as prognostic tools in PC.
Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo

Acute-on-chronic liver failure (ACLF) is characterized by undermined liver function, massive necrosis/apoptosis of hepatocytes, and hepatic inflammatory cell recruitment, leading to multiorgan failure. Traditional Chinese medicine (TCM) has been widely applied in clinical and experimental studies of ACLF. In this study, 23 compounds with 6,386 drug targets were obtained from Wenyang Jiedu Huayu (WYJDHY), and 8,096 genes were identified as ACLF disease targets, among which 3,132 were overlapping co-targets. Expression profile analysis identified 105 DEGs among the co-targets, which were associated with biological activities such as lymphocyte activation, immune response regulation, and pathways such as Th17 cell differentiation and NF-κB signaling. After PPI analysis and network construction, atractylenolide I (AT-1) has been identified as the hub active ingredient of the WYJDHY formula. LPS stimulation inhibited rat hepatocytes’ BRL 3A cell viability, promoted cell apoptosis, increased the levels of ALT, AST, IL-6, and VCAM-1 within the culture medium, and activated NF-κB signaling, whereas AT-1 treatment significantly attenuated LPS-induced toxicity on BRL 3A cells. Furthermore, the NF-κB signaling inhibitor PDTC exerted effects on LPS-stimulated BRL 3A cells similar to those of AT-1, and the combination of PDTC and AT-1 further attenuated LPS-induced toxicity on BRL 3A cells. In vivo, AT-1 alone or with PDTC improved the symptoms and local inflammation in ACLF model rats. In conclusion, 23 active ingredients of six herbs in the WYJDHY formula were retrieved, and 105 co-targets were differentially expressed in ACLF. AT-1 exerts protective effects on LPS-stimulated hepatocytes and ACLF rats, possibly by inhibiting the NF-κB pathway.
Toward evidence-based decision support systems to optimize pollination and yields in highbush blueberry

Highbush blueberry (Vaccinium spp.) is a globally important fruit crop that depends on insect-mediated pollination to produce quality fruit and commercially viable yields. Pollination success in blueberry is complex and impacted by multiple interacting factors including flower density, bee diversity and abundance, and weather conditions. Other factors, including floral traits, bee traits, and economics also contribute to pollination success at the farm level but are less well understood. As blueberry production continues to expand globally, decision-aid technologies are needed to optimize and enhance the sustainability of pollination strategies. The objective of this review is to highlight our current knowledge about blueberry pollination, where current research efforts are focused, and where future research should be directed to successfully implement a comprehensive blueberry pollination decision-making framework for modern production systems. Important knowledge gaps remain, including how to integrate wild and managed pollinators to optimize pollination, and how to provide predictable and stable crop pollination across variable environmental conditions. In addition, continued advances in pesticide stewardship are required to optimize pollinator health and crop outcomes. Integration of on- and off-farm data, statistical models, and software tools could distill complex scientific information into decision-aid systems that support sustainable, evidence-based pollination decisions at the farm level. Utility of these tools will require multi-disciplinary research and strategic deployment through effective extension and information-sharing networks of growers, beekeepers, and extension/crop advisors.
Identifying lncRNA–disease association based on GAT multiple-operator aggregation and inductive matrix completion

Computable models as a fundamental candidate for traditional biological experiments have been applied in inferring lncRNA–disease association (LDA) for many years, without time-consuming and laborious limitations. However, sparsity inherently existing in known heterogeneous bio-data is an obstacle to computable models to improve prediction accuracy further. Therefore, a new computational model composed of multiple mechanisms for lncRNA–disease association (MM-LDA) prediction was proposed, based on the fusion of the graph attention network (GAT) and inductive matrix completion (IMC). MM-LDA has two key steps to improve prediction accuracy: first, a multiple-operator aggregation was designed in the n-heads attention mechanism of the GAT. With this step, features of lncRNA nodes and disease nodes were enhanced. Second, IMC was introduced into the enhanced node features obtained in the first step, and then the LDA network was reconstructed to solve the cold start problem when data deficiency of the entire row or column happened in a known association matrix. Our MM-LDA achieved the following progress: first, using the Adam optimizer that adaptively adjusted the model learning rate could increase the convergent speed and not fall into local optima as well. Second, more excellent predictive ability was achieved against other similar models (with an AUC value of 0.9395 and an AUPR value of 0.8057 obtained from 5-fold cross-validation). Third, a 6.45% lower time cost was consumed against the advanced model GAMCLDA. In short, our MM-LDA achieved a more comprehensive prediction performance in terms of prediction accuracy and time cost.
Systematic review and meta-analysis of oral squamous cell carcinoma associated oral microbiome

The intersection between the human oral microbiome and oral health is an emerging area of study which has gained momentum over the last decade. This momentum has motivated a search for associations between the oral microbiome and oral cancer, in hopes of identifying possible biomarkers that facilitate earlier diagnosis and improved prognosis for patients with that disease. The present study examined the relationship between the microbiome in the human oral cavity and oral squamous cell carcinoma (OSCC). We searched the literature for case-control studies which focused on the relationship between the human oral microbiome and OSCC. We aggregated three types of data from these studies: bacteriome data at the genus level, predicted functional pathway data, and gene abundance data. From these data, we noted several microbial genera which may be associated with oral cancer status, including Fusobacterium. We also identified functional pathways which merit further investigation, including RNA degradation (ko03018) and primary immunodeficiency (ko05340). In addition, our analysis of gene abundance data identified the gene K06147 (ATP-binding cassette, subfamily B, bacterial) as being over abundant in OSCC samples. Our results are generalizations which identified some currents that we believe could guide further research. Our work faced several limitations related to the heterogeneity of the available data. Wide variation in methods for sample collection, methods for controlling for known behavioral risk factors, computing platform choice, and methods for case-control design all posed confounding factors in this work. We examined the current methods of data collection, data processing, and data reporting in order to offer suggestions toward the establishment of best practices within this field. We propose that these limitations should be addressed through the implementation of standardized data analytic practices that will conform to the rigor and reproducibility standards required of publicly funded research.
Theoretical conceptualization of online privacy-related decision making – Introducing the tripartite self-disclosure decision model

Self-disclosures on online social networks have received increased attention in the last two decades. Researchers from different disciplines investigated manifold influencing variables, and studies applied different theories to explain why many users share very sensitive and personal information despite potential risks and negative consequences, whereas others do not. Oftentimes, it is argued that self-disclosure decisions result from a kind of rational “calculus” of risks and benefits. However, such an assumption of rationality can and has been criticized. Nevertheless, fundamental cognitive and affective mechanisms that underlie self-disclosure decision making on social networks are still under-explored. By building upon previous self-disclosure theories and models, dual-and tripartite-system perspectives of decision making, and former empirical findings, we propose a Tripartite Self-Disclosure Decision (TSDD) model that conceptualizes inner processes of online self-disclosure decision making. Central to this model is the proposed interaction of three neural and cognitive/affective systems: a reflective, an impulsive, and an interoceptive system. We further highlight individual and environmental features, which can impact individuals’ online self-disclosure decisions by (interactively) influencing the proposed inner decision-making processes targeting the aforementioned three systems. Possible short- and long-term consequences are also discussed, which in turn can affect certain model components in subsequent self-disclosure decision situations. By taking such a neurocognitive perspective, we expand current research and models, which helps to better understand potentially risky information sharing on online social networks and can support attempts to prevent users from incautious self-disclosures.
Options for states to constrain pricing power of health care providers

Health care is becoming increasingly unaffordable for both individuals and employers and prices vary in nearly incomprehensible ways that do not correlate with quality. In many areas, consolidation of insurers and providers resulted in market failure that needs policy interventions. With federal gridlock, state policymakers are seeking options for controlling health care costs in markets where competition has failed. In this article, we discuss a spectrum of options that policymakers have to more directly control healthcare prices: (1) establishing a cost-growth benchmark, (2) creating a public option, (3) capping or establishing a default out-of-network payment rate for health care services, (4) creating affordability standards that authorize the insurance commissioner to reject contracts with excessive rate increases, (5) creating global budgets for hospital-based care, (6) capping excessive prices and/or tiering allowed rate updates, and (7) creating a population-based payment model. We provide a roadmap for state policymakers to consider these options, review the experiences with states who have tried these models, and discuss additional design considerations that policymakers should consider with any of these models. In the 1970's and 1980's, during a time of rapid growth in health care prices and spending, states took a decisive leadership role in developing regulatory models to curb the growth in health care costs and improve affordability for their citizens. It is time for states to lead the nation once again in addressing the current health care cost and affordability crisis in the U.S.
Psychopathological and neuropsychological disorders associated with chronic primary visceral pain: Systematic review

The World Health Organization (WHO), in its last review of its International Classification of Diseases, established a new classification for chronic pain. Among the principal categories, of particular interest is chronic primary pain as a new type of diagnosis in those cases in which the etiology of the disease is not clear, being termed as chronic primary visceral pain when it is situated in the thorax, abdomen, or pelvis. Due to the novelty of the term, the objective of the systematic review was to examine the psychopathological and neuropsychological disorders associated with chronic primary visceral pain. We carried out a search of the scientific literature following the PRISMA directives using the Pubmed, Medline, PsycInfo and Scopus databases. A total of 33 articles were selected after applying the inclusion and exclusion criteria. The analysis of the studies showed that most persons with chronic primary visceral pain suffer from at least one psychological disorder; the most prevalent being anxiety, depressive or somatoform disorders. The most frequent psychopathological symptoms are anxiety, depression and somatization. Similarly, the findings are insufficient to determine the existence of deficits in the domains of executive functioning, memory and intelligence. However, the existence of attention biases does seem to be clear. This review supposes a starting point for conceptualizing chronic primary visceral pain. It is necessary to continue further research so as to obtain a better understanding of this pathology and the disorders associated.
The role of BMP4 in adipose-derived stem cell differentiation: A minireview

Bone morphogenetic protein 4 (BMP4) is a member of the transforming growth factor beta (TGF-β) superfamily of cytokines responsible for stem cells’ commitment to differentiation, proliferation, and maturation. To date, various studies have utilized BMP4 as a chemical inducer for in vitro differentiation of human mesenchymal stem cells (MSCs) based on its potential. BMP4 drives in vitro differentiation of ADSC via TGF-β signaling pathway by interactions with BMP receptors leading to the activation of smad-dependent and smad-independent pathways. The BMP4 signaling pathways are regulated by intracellular and extracellular BMP4 antagonists. Extracellular BMP4 antagonist prevents interaction between BMP4 ligand to its receptors, while intracellular BMP4 antagonist shutdowns the smad-dependent pathways through multiple mechanisms. BMP4 proved as one of the popular differentiation factors to induce ADSC differentiation into cell from mesodermal origin. However, addition of all-trans retinoic acid is also needed in trans-differentiation of ADSC into ectodermal lineage cells. Suggesting that both BMP4 and RA signaling pathways may be necessary to be activated for in vitro trans-differentiation of ADSC.
Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

In the era of organ machine perfusion, experimental models to optimize reconditioning of (marginal) liver grafts are needed. Although the relevance of cytokine signatures in liver transplantation has been analyzed previously, the significance of molecular monitoring during normothermic machine perfusion (NMP) remains elusive. Therefore, we developed a porcine model of cold ischemic liver graft injury after prolonged static cold storage (SCS) and subsequent NMP: Livers obtained from ten minipigs underwent NMP for 6 h directly after procurement (control group) or after 20 h of SCS. Grafts after prolonged SCS showed significantly elevated AST, ALT, GLDH and GGT perfusate concentrations, and reduced lactate clearance. Bile analyses revealed reduced bile production, reduced bicarbonate and elevated glucose concentrations after prolonged SCS. Cytokine analyses of graft perfusate simultaneously demonstrated an increase of pro-inflammatory cytokines such as Interleukin-1α, Interleukin-2, and particularly Interleukin-18. The latter was the only significantly elevated cytokine compared to controls, peaking as early as 2 h after reperfusion (11,012 ng/ml vs. 1,493 ng/ml; p = 0.029). Also, concentrations of High-Mobility-Group-Protein B1 were significantly elevated after 2 h of reperfusion (706.00 ng/ml vs. 148.20 ng/ml; p < 0.001) and showed positive correlations with AST (r 2 = 0.846) and GLDH (r 2 = 0.918) levels. Molecular analyses during reconditioning of liver grafts provide insights into the degree of inflammation and cell damage and could thereby facilitate future interventions during NMP reducing acute and chronic graft injury. Graphical Abstract
HRas and Myc synergistically induce cell cycle progression and apoptosis of murine cardiomyocytes

Aim Adult mammalian cardiomyocytes are incapable of significant proliferation, limiting regeneration after myocardial injury. Overexpression of the transcription factor Myc has been shown to drive proliferation in the adult mouse heart, but only when combined with Cyclin T1. As constitutive HRas activity has been shown to stabilise Cyclin T1 in vivo, we aimed to establish whether Myc and HRas could also act cooperatively to induce proliferation in adult mammalian cardiomyocytes in vivo. Methods and results Using a genetically modified mouse model, we confirmed that constitutive HRas activity (HRasG12V) increased Cyclin T1 expression. HRasG12V and constitutive Myc expression together co-operate to drive cell-cycle progression of adult mammalian cardiomyocytes. However, stimulation of endogenous cardiac proliferation by the ectopic expression of HRasG12V and Myc also induced cardiomyocyte death, while Myc and Cyclin T1 expression did not. Conclusion Co-expression of Cyclin T1 and Myc may be a therapeutically tractable approach for cardiomyocyte neo-genesis post injury, while cell death induced by HRasG12V and Myc expression likely limits this option as a regenerative therapeutic target.