Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Oligomers - From Protein Binding to Probabilistic Modelling

This dissertation focuses on rationalised DNA design as a tool for the discovery and development of new therapeutic entities, as well as understanding the biological function of DNA beyond the storage of genetic information. The study is comprised of two main areas of study: (i) the use of DNA as a coding unit to illustrate the relationship between code-diversity and dynamics of self-assembly; and (ii) the use of DNA as an active unit that interacts and regulates a target protein. In the study of DNA as a coding unit in code-diversity and dynamics of self-assembly, we developed the DNA-Based Diversity Modelling and Analysis (DDMA) method. Using Polymerase Chain Reaction (PCR) and Real Time Polymerase Chain Reaction (RT-PCR), we studied the diversity and evolution of synthetic oligonucleotide populations. The manipulation of critical conditions, with monitoring and interpretation of their effects, lead to understanding how PCR amplification unfolding could reshape a population. This new take on an old technology has great value for the study of: (a) code-diversity, convenient in a DNA-based selection method, so semi-quantitation can evaluate a selection development and the population’s behaviour can indicate the quality; (b) self-assembly dynamics, for the simulation of a real evolution, emulating a society where selective pressures direct the population’s adaptation; and (c) development of high-entropy DNA structures, in order to understand how similar unspecific DNA structures are formed in certain pathologies, such as in auto-immune diseases.
Explaining stock markets' performance during the COVID‐19 crisis: Could Google searches be a significant behavioral indicator?

Summary The purpose of this study is to examine the impact of the pandemic on the performance of stock markets, focusing on the behavioral influence of the fear due to COVID‐19. Using a data set of 10 developed countries during the period December 31, 2019, to September 30, 2020, we examine the impact of COVID‐19 on the performance of the stock markets. We incorporate the impact of the COVID‐19 pandemic using the following variables: (a) the number of new COVID‐19 cases, which was widely used as the main explanatory variable for market performance in early financial studies, and (b) a Google Search index, which collects the number of Google searches related to COVID‐19 and incorporates the health risk and the fear of COVID‐19 (the higher the number of searches for Covid terms, the higher the index value, and the higher the fear index). We employ our input into an EGARCH(1,1,1) model, and the findings show that the Google Search index enables us to draw statistically significant information regarding the impact of the COVID‐19 fear on the performance of the stock markets. On the other hand, the variable of the number of new COVID‐19 cases does not have any statistically significant influence on the performance of the stock markets. Google searches could be a useful tool for supporters of behavioral finance, scholars, and practitioners.
Local neuronal relational structures underlying the contents of human conscious experience

Abstract While most theories of consciousness posit some kind of dependence on global network activities, I consider here an alternative, localist perspective—in which localized cortical regions each underlie the emergence of a unique category of conscious experience. Under this perspective, the large-scale activation often found in the cortex is a consequence of the complexity of typical conscious experiences rather than an obligatory condition for the emergence of conscious awareness—which can flexibly shift, depending on the richness of its contents, from local to more global activation patterns. This perspective fits a massive body of human imaging, recordings, lesions and stimulation data but opens a fundamental problem: how can the information, defining each content, be derived locally in each cortical region. Here, I will discuss a solution echoing pioneering structuralist ideas in which the content of a conscious experience is defined by its relationship to all other contents within an experiential category. In neuronal terms, this relationship structure between contents is embodied by the local geometry of similarity distances between cortical activation patterns generated during each conscious experience, likely mediated via networks of local neuronal connections. Thus, in order for any conscious experience to appear in an individual’s mind, two central conditions must be met. First, a specific configural pattern (“bar-code”) of neuronal activity must appear within a local relational geometry, i.e. a cortical area. Second, the individual neurons underlying the activated pattern must be bound into a unified functional ensemble through a burst of recurrent neuronal firing: local “ignitions”.
Cyclovirobuxine inhibits the progression of clear cell renal cell carcinoma by suppressing the IGFBP3-AKT/STAT3/MAPK-Snail signalling pathway

Of all pathological types of renal cell cancer (RCC), clear cell renal cell carcinoma (ccRCC) has the highest incidence. Cyclovirobuxine (CVB), a triterpenoid alkaloid isolated from Buxus microphylla, exhibits antitumour activity against gastric cancer and breast cancer; however, the mechanism by which CVB inhibits ccRCC remains unclear. The aim of our study was to explore the antitumour effects of CVB on ccRCC and to elucidate its exact mechanism. Cell viability, proliferation, cell cycle distribution, apoptosis, wound healing and invasion were evaluated. Furthermore, Western blotting, immunofluorescence staining, immunohistochemical staining, and bioinformatics analyses were utilized to comprehensively probe the molecular mechanisms. The in vivo curative effect of CVB was explored using a 786-O xenograft model established in nude mice. CVB reduced cell viability, proliferation, angiogenesis, the epithelial-mesenchymal transition (EMT), migration and invasion. In addition, CVB induced cell cycle arrest in S phase and promoted apoptosis. The expression of the EMT-related transcription factor Snail was significantly downregulated by CVB via the inhibition of the AKT, STAT3 and MAPK pathways. We revealed that insulin-like growth factor binding protein 3 (IGFBP3) was the true therapeutic target of CVB. CVB exerted anti-ccRCC effects by blocking the IGFBP3-AKT/STAT3/MAPK-Snail pathway. Targeted inhibition of IGFBP3 with CVB treatment may become a promising therapeutic regimen for ccRCC.
Integrative Epigenome Map of the Normal Human Prostate Provides Insights Into Prostate Cancer Predisposition

Cells of all tissues in the human body share almost the exact same DNA sequence, but the epigenomic landscape can be drastically distinct. To improve our understanding of the epigenetic abnormalities in prostate-related diseases, it is important to use the epigenome of normal prostate as a reference. Although previous efforts have provided critical insights into the genetic and transcriptomic features of the normal prostate, a comprehensive epigenome map has been lacking. To address this need, we conducted a Roadmap Epigenomics legacy project integrating six histone marks (H3K4me1, H3K4me3, H3K9me3, H3K36me3, H3K27me3, and H3K27ac) with complete DNA methylome, transcriptome, and chromatin accessibility data to produce a comprehensive epigenome map of normal prostate tissue. Our epigenome map is composed of 18 chromatin states each with unique signatures of DNA methylation, chromatin accessibility, and gene expression. This map provides a high-resolution comprehensive annotation of regulatory regions of the prostate, including 105,593 enhancer and 70,481 promoter elements, which account for 5.3% of the genome. By comparing with other epigenomes, we identified 7,580 prostate-specific active enhancers associated with prostate development. Epigenomic annotation of GWAS SNPs associated with prostate cancers revealed that two out of nine SNPs within prostate enhancer regions destroyed putative androgen receptor (AR) binding motif. A notable SNP rs17694493, might decouple AR’s repressive effect on CDKN2B-AS1 and cell cycle regulation, thereby playing a causal role in predisposing cancer risk. The comprehensive epigenome map of the prostate is valuable for investigating prostate-related diseases.
Development and External Verification of a Nomogram for Patients with Persistent Acute Kidney Injury in the Intensive Care Unit

Background We aimed to identify the affecting features of persistent acute kidney injury (pAKI) for patients in intensive care units (ICU). Methods The Medical Information Mart for Intensive Care IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD) were used to identify AKI patients with and without duration of more than 48 hours. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM-RFE) were utilized to screen for the significant clinical indexes associated with pAKI. Predictive nomogram was created based on the above informative parameters to predict the probability of pAKI. Results LASSO regression and SVM-RFE revealed that serum albumin, chronic kidney disease, AKI stage, sequential organ failure assessment score, lactate and renal replacement therapy during the first day were significantly associated with pAKI in the training cohort. The predictive nomogram based on the six predictors exhibited good predictive performance as calculated by C-index 0.730 (95% CI 0.710–0.749) in the training group, 0.702 (95% CI 0.672–0.722) in the internal validation set and 0.704 (0.677–0.731) in the external validation cohort for the prediction of pAKI. Moreover, the predictive nomogram exhibited not only encouraging calibration ability, but also great clinical utility in the training group, in the internal validation group as well as in the external validation cohort. Conclusion Serum albumin, CKD, AKI stage, SOFA score, lactate, RRT during the first day were closely associated with pAKI in patients in ICU. The predictive nomogram for pAKI manifested good predictive ability for the identification of ICU patients with pAKI.
The Cut-Off Score of Four Clinical Tests to Quantify Balance Impairment in Individuals with Chronic Ankle Instability

Background Balance impairment is a common consequence of chronic ankle instability (CAI). This study aimed to assess the discriminative validity of four clinical tests for quantifying balance impairment in individuals with CAI. Methods Participants were screened for their balance using the single-leg balance test (SLBT) and were assigned to either the positive or the negative SLBT groups. Fifty-four individuals with CAI (N = 27 per group) were recruited and completed four clinical tests including the foot-lift test (FLT), the time-in-balance test (TIBT), the modified star excursion balance test in the posteromedial (mSEBT-PM) direction and the side-hop test (SHT). The receiver operating characteristics (ROC) curve coupled with Youden index were calculated to determine the optimal cut-off scores of each test. Results We found significant differences in balance between groups for all tests, with good to excellent values for the area under the ROC curve (AUC). All four tests reached good to excellent sensitivity and specificity values and had significant cut-off scores to discriminate balance performance among CAI participants. Conclusion All four clinical tests can be conducted with their respective cut-off scores to quantify balance impairment in individuals with CAI.
Compulsive Internet Use Scale: Psychometric Properties and Associations With Sleeping Patterns, Mental Health, and Well-Being in Lithuanian Medical Students During the Coronavirus Disease 2019 Pandemic

Background: The increase in problematic Internet use (PIU) among medical students and resident doctors during the coronavirus disease 2019 (COVID-19) pandemic may be leading to significant impairments in everyday functioning, including sleeping patterns, anxiety, depressive symptoms, and overall well-being. The Compulsive Internet Use Scale (CIUS) has been developed to assess the severity of PIU, however, it has not been elucidated whether this scale is also applicable to medical students and resident doctors. The first aim of this study was to explore the psychometric properties of the Lithuanian version of the CIUS. The second aim was to examine associations between subjectively reported mental health symptoms and PIU during the COVID-19 pandemic. Methods: A total of 524 medical students and resident doctors (78.60% women, mean age 24 [SD 3] years old) participated in an online survey between December 2020 and February 2021. Participants completed the CIUS, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder Assessment-7 (GAD-7), and the WHO—Five Well-Being Index questionnaire (WHO-5). Results: The confirmatory factor analysis (CFA) suggested brief versions (CIUS-5, CIUS-7, and CIUS-9) rather than the original (CIUS-14) version of the CIUS questionnaire as reliable and structurally stable instruments that can be used to measure compulsive Internet use severity in the sample of medical students and resident doctors. The most prevalent online behaviors were social media use (90.1%), online shopping (15.6%), and online gaming/gambling (11.3%). Students with higher CIUS scores reported significantly lower academic achievements during the 6 months (r = 0.12–0.13; p < 0.006), as well as more severe depressive and anxiety symptoms, worsened sleep quality, and lower sense of well-being (r = 0.21–0.41; p's < 0.001). Both, during workdays (d = 0.87) and weekend (d = 0.33), students spent more time online than resident doctors (p's < 0.001). Conclusion: The brief, 5-, 7-, and 9-item versions of the Lithuanian CIUS are reliable and valid self-report screening instruments for evaluating the severity of PIU symptoms among the medical student population. Symptoms of PIU during the COVID-19 period were associated with worsened self-reported mental health and everyday functioning.
Effect of wetting agent coverage on the surface properties of resin composite submitted to brushing and staining cycles

Background Wetting agents facilitate the composites handling, acting as a lubricant and decreasing their stickness to spatula. The effects of these materials on the properties of composites are not completely clear. This study aimed to evaluate Gloss, Color, Roughness and Microhardness of a composite (Filtek Z250 XT, 3M Oral Care) covered by a wetting agent (Modeling Resin, Bisco), submitted to brushing and staining cycles with red wine. Material and Methods Cylinder-shaped samples (8 mm ø x 2 mm height) were divided into 4 groups, according to application of wetting agent and brushing cycles (n = 20). The composite was placed in the orifice of a polytetrafluoroethylene mold, received wetting agent coverage, and was light-cured. Gloss, Color, Roughness and Microhardness were evaluated in two times: after samples confection and after brushing + staining cycles. Data were submitted to one-way ANOVA and Tukey’s test (ΔL, Δa, Δb and ΔE) and two-way repeated measures ANOVA and Bonferronis’s test (gloss, roughness and microhardness). Results In general, the composite showed higher gloss values when added by the wetting agent. No statistical differences were observed regarding colors’ groups. Roughness increased after brushing cycles, regardless of wetting agent application. The only group which presented decreased Microhardness after cycles was the group without wetting agent, only submitted to staining with red wine. Conclusions The application of wetting agent on the composite did not interfere negatively with its properties of Gloss, Color, Roughness and Microhardness. Key words:Resin composite, wetting agent, surface properties, gloss, color, esthetic dentistry.
The effect of bacterial cellulose nanocrystals on the shear bond strength of resin modified glass ionomer cement to dentin

Background The present study aimed to investigate the effect of bacterial cellulose nanocrystals (BCNC) on the shear bond strength (SBS) of resin modified glass ionomer cement (RMGIC) to dentin. Material and Methods A total of 48 freshly extracted intact third molars were randomly divided into four main groups with three different concentrations (0.3%, 0.5% and 1% wt) of BCNC with RMGIC and control group without BCNC. These specimens were kept in distilled water at 37° C for 24h. Shear bond strength was examined, using the universal testing machine. Kruskal-Wallis test and Dunn`s post-hoc test were applied for analysis of data. P<0.05 was considered as the level of significance. Results The addition of a 1%wt of BCNC to the RMGIC led to a significant increase in the shear bond strength (7.17 ± 2.14) compared to the control group (2.09 ± 1.80) (P=0.007). The shear bond strength was improved up to 343%. Conclusions It was found that the incorporation of 1% wt BCNC to the RMGICs enhanced the SBS properties of the RMGIC significantly. Modifying RMGIC with BCNC might be advantageous in terms of improving the restorative material. Key words:Bacterial cellulose nanocrystals, RMGIC, Shear bond strength.
EAD-Net: A Novel Lesion Segmentation Method in Diabetic Retinopathy Using Neural Networks

Diabetic retinopathy (DR) is a common chronic fundus disease, which has four different kinds of microvessel structure and microvascular lesions: microaneurysms (MAs), hemorrhages (HEs), hard exudates, and soft exudates. Accurate detection and counting of them are a basic but important work. The manual annotation of these lesions is a labor-intensive task in clinical analysis. To solve the problem, we proposed a novel segmentation method for different lesions in DR. Our method is based on a convolutional neural network and can be divided into encoder module, attention module, and decoder module, so we refer it as EAD-Net. After normalization and augmentation, the fundus images were sent to the EAD-Net for automated feature extraction and pixel-wise label prediction. Given the evaluation metrics based on the matching degree between detected candidates and ground truth lesions, our method achieved sensitivity of 92.77%, specificity of 99.98%, and accuracy of 99.97% on the e_ophtha_EX dataset and comparable AUPR (Area under Precision-Recall curve) scores on IDRiD dataset. Moreover, the results on the local dataset also show that our EAD-Net has better performance than original U-net in most metrics, especially in the sensitivity and F1-score, with nearly ten percent improvement. The proposed EAD-Net is a novel method based on clinical DR diagnosis. It has satisfactory results on the segmentation of four different kinds of lesions. These effective segmentations have important clinical significance in the monitoring and diagnosis of DR.
Analysis of Predictive Risk Factors in Aquaporin-4-IgG Positive Highly Active Neuromyelitis Optica Spectrum Disorders

Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory diseases with a high risk of recurrence and progressive disability, and it is crucial to find sensitive and reliable biomarkers for prognosis and the early prediction of relapse. Highly active NMOSD is defined as two or more clinical relapses within a 12-month period. In this study, we analyzed independent risk factors among patients with aquaporin-4 (AQP4)-IgG positive highly active NMOSD. In this retrospective study, we analyzed the data of 94 AQP4-IgG positive patients with highly active NMOSD and 105 AQP4-IgG positive controls with non-highly active NMOSD. In order to rule out possible effects of previous treatments (such as glucocorticoids, immunoglobulin, and immunosuppressants), we focused on the first-attack NMOSD patients admitted to our hospital. Clinical data, including the age of onset, gender, comorbidities, and serum analysis and cerebrospinal fluid (CSF) analysis results, were collected, after which logistic regression models were used to determine the associations between the clinical factors and relapse outcomes. The prevalence of connective tissue disease and the proportion of antinuclear antibody (ANA)-positivity were higher in the highly active NMOSD group than in the control group. The leukocyte counts, homocysteine (Hcy) levels, CSF leukocyte counts, protein concentrations, IgG indexes, and 24h IgG synthesis rates were also higher in the highly active NMOSD group. The results of multivariate analysis indicated that connective tissue disease comorbidity (OR = 5.953, 95% CI: 1.221–29.034, P = 0.027), Hcy levels (OR = 1.063, 95% CI: 1.003–1.126, P = 0.04), and 24h IgG synthesis rate (OR = 1.038, 95% CI: 1.003–1.075, P = 0.034) may be independent risk factors for AQP4-IgG positive highly active NMOSD relapse after adjusting for various variables. Comorbidity of connective tissue disease, Hcy levels, and 24h IgG synthesis rate may be independent risk factors for AQP4-IgG positive highly active NMOSD.
The Clinical Significance of Changes in Serum New Cytokine CYTL1 in Patients with Knee Osteoarthritis

Objective The present study aims to investigate the clinical significance of changes in the expression of new cytokine-like 1 (CYTL1) in the serum of patients with knee osteoarthritis (KOA). Methods A total of 182 patients with KOA, including 84 males and 98 females aged 39–86 with an average age of 66.4 ± 9.7 and an average body mass index (BMI) of 24.9 ± 2.4 kg/m2, were enrolled in the study. The patients were divided into three subgroups: the grade II subgroup (n = 23), grade III subgroup (n = 63), and grade IV subgroup (n = 96) based on severity, as calculated by the Kellgren and Lawrence (K&L) classification system. In addition, 152 volunteers from our health center who came in for physical examination were selected as the control group, including 70 males and 82 females aged 37–82 with an average age of 63.4 ± 9.5 and an average BMI of 24.8 ± 2.2 kg/m2. An enzyme-linked immunosorbent assay was adopted to detect the serum CYTL1 levels, and the correlation between CYTL1 and the severity of KOA was analyzed. Results The serum level of CYTL1 was significantly lower in the KOA group than in the control group (P < 0.05). In the KOA group, the difference in the serum level of CYTL1 was statistically significant between the subgroups and decreased significantly with an increase in the severity of the disease (F = 54.826, P < 0.001). Therefore, the serum level of CYTL1 was correlated with the severity of the disease, as determined by the K&L classification system (r = −0.613, P < 0.001). Conclusion The serum levels of CYTL1 are strongly correlated with the severity of the disease in patients with KOA and could be a new therapeutic target for KOA.