Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioinformatics Analysis of ZBTB16 as a Prognostic Marker for Ewing's Sarcoma

Objective The purpose of this study is to identify novel biomarkers for the prognosis of Ewing's sarcoma based on bioinformatics analysis. Methods The GSE63157 and GSE17679 datasets contain patient and healthy control microarray data that were downloaded from the Gene Expression Omnibus (GEO) database and analyzed through R language software to obtain differentially expressed genes (DEGs). Firstly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, protein-protein interaction (PPI) networks, and Cytoscape Molecular Complex Detection (MCODE) plug-in were then used to compute the highest scores of the module. After survival analysis, the hub genes were lastly obtained from the two module genes. Results A total of 1181 DEGs were identified from the two GSEs. Through MCODE and survival analysis, we obtain 53 DEGs from the module and 29 overall survival- (OS-) related genes. ZBTB16 was the only downregulated gene after Venn diagrams. Survival analysis indicates that there was a significant correlation between the high expression of ZBTB16 and the OS of Ewing's sarcoma (ES), and the low expression group had an unfavorable OS when compared to the high expression group. Conclusions High expression of ZBTB16 may serve as a predictor biomarker of poor prognosis in ES patients.
IFNG, FCER1A, PCDHB10 expression as a new potential marker of efficacy in grass pollen allergen-specific immunotherapy

Introduction Allergen-specific immunotherapy (AIT) is the core treatment in allergic rhinitis and asthma. Although widely used, some patients do not benefit from treatment and there is no efficacy objective marker. Aim To define the profile of gene transcripts during the build-up phase of AIT and their comparison to the control group and then search for a viable efficacy marker in relation to patient symptoms. Material and methods AIT was administered in 22 patients allergic to grass pollen. Analysis of 15 selected transcript expression was performed in whole blood samples taken before AIT (sample A) and after reaching the maintenance dose (sample B). The control group included 25 healthy volunteers (sample C). The primary endpoint was Relative Quantification. The gene expression analysis was followed by clinical evaluation with the use of Allergy Control Score (ACS). Results Comparison between samples A and B of gene expression showed a significant increase in IFNG expression (p = 0.03). In relation to the control group, pretreatment samples from patients showed higher levels of AFAP1L1 (p = 0.006), COMMD8 (p = 0.001), PIK3CD (p = 0.027) and TWIST2 (p = 0.0003) in univariate analysis. A generalized linear regression model was built according to the Bayesian Information Criterion based on the IFNG, FCER1A and PCDHB10 expression pattern for prediction of the AIT outcome. The model showed a correlation in predicted and observed changes in ACS. Conclusions There is a significant change in the expression of IFNG during the build-up phase of AIT. The authors propose an in vitro model of AIT efficacy prediction for further validation.
Machine Learning Techniques for Personalised Medicine Approaches in Immune-Mediated Chronic Inflammatory Diseases: Applications and Challenges

In the past decade, the emergence of machine learning (ML) applications has led to significant advances towards implementation of personalised medicine approaches for improved health care, due to the exceptional performance of ML models when utilising complex big data. The immune-mediated chronic inflammatory diseases are a group of complex disorders associated with dysregulated immune responses resulting in inflammation affecting various organs and systems. The heterogeneous nature of these diseases poses great challenges for tailored disease management and addressing unmet patient needs. Applying novel ML techniques to the clinical study of chronic inflammatory diseases shows promising results and great potential for precision medicine applications in clinical research and practice. In this review, we highlight the clinical applications of various ML techniques for prediction, diagnosis and prognosis of autoimmune rheumatic diseases, inflammatory bowel disease, autoimmune chronic kidney disease, and multiple sclerosis, as well as ML applications for patient stratification and treatment selection. We highlight the use of ML in drug development, including target identification, validation and drug repurposing, as well as challenges related to data interpretation and validation, and ethical concerns related to the use of artificial intelligence in clinical research.
Efflux Pump Activity and Mutations Driving Multidrug Resistance in Acinetobacter baumannii at a Tertiary Hospital in Pretoria, South Africa

Acinetobacter baumannii (A. baumannii) has developed several resistance mechanisms. The bacteria have been reported as origin of multiple outbreaks. This study aims to investigate the use of efflux pumps and quinolone resistance-associated genotypic mutations as mechanisms of resistance in A. baumannii isolates at a tertiary hospital. A total number of 103 A. baumannii isolates were investigated after identification and antimicrobial susceptibility testing by VITEK2 followed by PCR amplification of blaOXA-51. Conventional PCR amplification of the AdeABC efflux pump (adeB, adeS, and adeR) and quinolone (parC and gyrA) resistance genes were performed, followed by quantitative real-time PCR of AdeABC efflux pump genes. Phenotypic evaluation of efflux pump expression was performed by determining the difference between the MIC of tigecycline before and after exposure to an efflux pump inhibitor. The Sanger sequencing method was used to sequence the parC and gyrA amplicons. A phylogenetic tree was drawn using MEGA 4.0 to evaluate evolutionary relatedness of the strains. All the collected isolates were blaOXA-51-positive. High resistance to almost all the tested antibiotics was observed. Efflux pump was found in 75% of isolates as a mechanism of resistance. The study detected parC gene mutation in 60% and gyrA gene mutation in 85%, while 37% of isolates had mutations on both genes. A minimal evolutionary distance between the isolates was reported. The use of the AdeABC efflux pump system as an active mechanism of resistance combined with point mutation mainly in gyrA was shown to contribute to broaden the resistance spectrum of A. baumannii isolates.
What Is in the Field for Genetics and Epigenetics of Diabetic Neuropathy: The Role of MicroRNAs

Despite the high prevalence of diabetic neuropathy, its early start, and its impact on quality of life and mortality, unresolved clinical issues persist in the field regarding its screening implementation, the understanding of its mechanisms, and the search for valid biomarkers, as well as disease-modifying treatment. Genetics may address these needs by providing genetic biomarkers of susceptibility, giving insights into pathogenesis, and shedding light on how to select possible responders to treatment. After a brief summary of recent studies on the genetics of diabetic neuropathy, the current review focused mainly on microRNAs (miRNAs), including the authors' results in this field. It summarized the findings of animal and human studies that associate miRNAs with diabetic neuropathy and explored the possible pathogenetic meanings of these associations, in particular regarding miR-128a, miR-155a, and miR-499a, as well as their application for diabetic neuropathy screening. Moreover, from a genetic perspective, it examined new findings of polymorphisms of miRNA genes in diabetic neuropathy. It considered in more depth the pathogenetic implications for diabetic neuropathy of the polymorphism of MIR499A and the related changes in the downstream action of miR-499a, showing how epigenetic and genetic studies may provide insight into pathogenetic mechanisms like mitochondrial dysfunction. Finally, the concept and the data of genotype-phenotype association for polymorphism of miRNA genes were described. In conclusion, although at a very preliminary stage, the findings linking the genetics and epigenetics of miRNAs might contribute to the identification of exploratory risk biomarkers, a comprehensive definition of susceptibility to specific pathogenetic mechanisms, and the development of mechanism-based treatment of diabetic neuropathy, thus addressing the goals of genetic studies.
Probing the Peculiarity of EhRabX10, a pseudoRab GTPase, from the Enteric Parasite Entamoeba histolytica through In Silico Modeling and Docking Studies

Entamoeba histolytica (Eh) is a pathogenic eukaryote that often resides silently in humans under asymptomatic stages. Upon indeterminate stimulus, it develops into fulminant amoebiasis that causes severe hepatic abscesses with 50% mortality. This neglected tropical pathogen relies massively on membrane modulation to flourish and cause disease; these modulations range from the phagocytic mode for food acquisition to a complex trogocytosis mechanism for tissue invasion. Rab GTPases form the largest branch of the Ras-like small GTPases, with a diverse set of roles across the eukaryotic kingdom. Rab GTPases are vital for the orchestration of membrane transport and the secretory pathway responsible for transporting the pathogenic effectors, such as cysteine proteases (EhCPs) which help in tissue invasion. Rab GTPases thus play a crucial role in executing the cytolytic effect of E. histolytica. First, they interact with Gal/Nac lectins required for adhering to the host cells, and then, they assist in the secretion of EhCPs. Additionally, amoebic Rab GTPases are vital for encystation because substantial vesicular trafficking is required to create dormant amoebic cysts. These cysts are the infective agent and help to spread the disease. The absence of a “bonafide” vesicular transport machinery in Eh and the existence of a diverse repertoire of amoebic Rab GTPases (EhRab) hint at their contribution in supporting this atypical machinery. Here, we provide insights into a pseudoRab GTPase, EhRabX10, by performing physicochemical analysis, predictive 3D structure modeling, protein-protein interaction studies, and in silico molecular docking. Our group is the first one to classify EhRabX10 as a pseudoRab GTPase with four nonconserved G-motifs. It possesses the basic fold of the P-loop containing nucleotide hydrolases. Through this in silico study, we provide an introduction to the characterization of the atypical EhRabX10 and set the stage for future explorations into the mechanisms of nucleotide recognition, binding, and hydrolysis employed by the pseudoEhRab GTPase family.
An information-theory analysis of DNA methylation identifies converging genetic and epigenetic drivers of paediatric acute lymphoblastic leukaemia

In cancer, linking epigenetic alterations to drivers of transformation has been difficult, in part because DNA-methylation analyses must capture epigenetic variability, which is central to tumour heterogeneity and tumour plasticity. Here, by conducting a comprehensive analysis, based on information theory, of differences in methylation stochasticity in samples from patients with paediatric acute lymphoblastic leukaemia (ALL), we show that ALL epigenomes are stochastic, and marked by increased methylation entropy at specific regulatory regions and genes. By integrating data methylation and single-cell gene-expression data, we arrived at a relationship between methylation entropy and gene-expression variability, and found that epigenetic changes in ALL converge on a shared set of genes that overlap with genetic drivers involved in chromosomal translocations across the disease spectrum. Our findings suggest that an epigenetically driven gene- regulation network, with UHRF1 (ubiquitin-like with PHD and RING finger domains 1) as a central node, links genetic drivers and epigenetic mediators in ALL. data, and generated a comprehensive map of statistical properties of the methylomic landscape in ALL. We locally estimated probability distributions of the stochastic methylation state which, in addition to computing mean methylation levels, allowed us to quantify the amount of methylation stochasticity within genomic regions using the information-theoretic concept of Shannon entropy, evaluate the robustness of these distributions to changes in the potential energy landscape, and use these statistics to perform differential analysis with respect to normal samples. By employing the information-theoretic concept of mutual information, we also identified ‘informative’ regions of the genome characterized by statistically significant associations between their methylation level and the phenotype in our cancer/normal comparisons. Informative regions are of compelling interest when investigating epigenetic dysregulation in cancer since the probability distribution of the methylation state within these regions is significantly determined by the phenotype, pointing to the possibility that they may play an important role in tumor initiation and progression.
Soil urease inhibition by various plant extracts

Urea is the most popular and widely used nitrogenous fertilizer. High soil urease activity rapidly hydrolyses applied urea to ammonia which contributes to soil nitrogen (N) losses and reduces N use efficiency of crop plants. The ammonia losses can be minimized by the inhibition of soil urease activity which has been explored using various potential chemical inhibitors. However, the soil urease activity inhibition potential of plant extracts is rarely explored to date. In the present study, extracts of 35 plant materials were taken and evaluated against jack bean urease. Eleven extracts, showing >50% jack bean urease inhibition, were selected and further investigated in 13 soils collected from various districts of Punjab, Pakistan. Interestingly, except Capsicum annum, Melia azedarach, Citrus reticulata and Quercus infectoria, the plant extracts showed urease inhibition activities in soils, the extent of which was lower as compared to that observed in jack bean urease though. Maximum urea hydrolysis inhibition (70%) was noted with Vachellia nilotica which was 40% more than that of hydroquinone (50%) followed by that of Eucalyptus camaldulensis (24%). The extracts of V. nilotica and E. camaldulensis were coated on urea and applied to soil in the next step. At 21st day, 239% and 116% more urea-N was recovered from soil treated with V. nilotica and E. camaldulensis extracts coated urea, respectively, as compared to uncoated urea. Conclusively, these results indicated that the coating of V. nilotica and E. camaldulensis extracts on urea prills prolonged urea persistence in soil owing to minimum urea hydrolysis, probably, the extracts of V. nilotica and E. camaldulensis showed their urease inhibition potential. The results of this study provide a base line for the identification of new soil urease inhibitor compounds from plant materials in future.
Application of Intelligent Monitoring of Percutaneous Partial Oxygen Pressure in Evaluating the Evolution of Scar Hyperplasia

The study aimed to investigate the dynamic changes of percutaneous partial oxygen pressure during the development and evolution of a hypertrophic scar. Twenty cases of hypertrophic scar patients at different stages were selected. A percutaneous oxygen monitor was used to measure oxygen partial pressure in the scar and normal skin tissue at 14, 30, 60, and 90 days after surgery. The changes of oxygen partial pressure, tissue structure, HIF-1α, and VEGF expression in the scar tissue were observed, and the correlation was analyzed. In the scar maturation process, with the prolongation of time, the partial oxygen pressure in the tissue increased gradually. The expression intensity of HIF-1α and VEGF decreased gradually, HIF-1α was positively correlated with VEGF (r = 0.98, P < 0.01), there was a negative correlation between oxygen partial pressure and HIF-1 α expression (r = −0.92, P < 0.01), and it was negatively correlated with VEGF (r = −0.88, P < 0.01). TcPO2 measurement can be used to assess scar maturity; HIF-1 α and VEGF may play an essential role in regulating partial oxygen pressure in the scar tissue.
Association Between Pitch Break on the 4-Seam Fastball and Slider and Shoulder Injury in Major League Baseball Pitchers: A Case-Control Study

Background: Few specific risk factors are known for shoulder injury in professional pitchers. New pitch-tracking data allow for risk stratification based on advanced metrics. Purpose/Hypothesis: The purpose of this study was to determine the association between shoulder injury, pitch frequency, and pitch metrics (velocity, total break, break angle, and spin rate) for the 4-seam fastball, curveball, and slider. We hypothesized that more frequent use of the 4-seam fastball would be associated with shoulder injury. Study Design: Case-control study; Level of evidence, 3. Methods: The Major League Baseball (MLB) database was queried for pitchers who had been placed on the injury list (IL) with a shoulder injury between 2015 and 2019. Injured pitchers were matched 1:1 with controls (pitchers not on the IL with a shoulder injury during the study period), based on age (±1 year), history of ulnar collateral ligament reconstruction, position (starter vs reliever), and pitches thrown during the injury season (±500). Pitch frequency, velocity, horizontal break, vertical break, total break, and spin rate for the season were collected from the Baseball Savant website for the 4-seam fastball, curveball, and slider. Univariate analysis was used to determine group differences for individual variables. Multiple logistic regression was performed to determine odds ratios (ORs) for shoulder injury associated with pitch frequency, velocity, total break, break angle, and spin rate. Covariates included age, position, ulnar collateral ligament reconstruction status, expected weighted on-base average, and total pitches thrown. Results: Overall, 233 injured pitchers were evaluated. The most common reason for IL placement was inflammation (78/233; 33.5%) followed by strain or sprain (61/233; 26.2%). Increased total pitch break was associated with an increased risk of shoulder injury for the 4-seam fastball (OR, 1.340 [95% confidence interval (CI), 1.199-1.509]; P < . 001) and slider (OR, 1.360 [95% CI, 1.206-1.554]; P < .001). For the slider, a decreased spin rate (OR = 0.998 [95% CI, 0.997-0.999]; P = .026) and a more vertical break angle (OR = 1.170 [95% CI: 1.073-1.278]; P = .004) were associated with increased risk of injury. Conclusion: Increased pitch break of the 4-seam fastball and slider was associated positively with shoulder injury in MLB pitchers. These findings add to the understanding of throwing injury and ability to detect risk using ball-tracking technology.
Knowledge, attitude and practice of influenza vaccination among Lebanese parents: A cross-sectional survey from a developing country

Background A growing number of parents refuse vaccination due to concerns about side effects. Influenza vaccine is no exception and remains one of the most controversial vaccines. Data regarding influenza vaccine uptake and parental knowledge, attitude and practice towards vaccination in the Lebanese population is lacking. The aim of this study was to assess the rate of vaccination refusal and potential associated factors among Lebanese parents of school-aged children, in general and with a focus on influenza vaccine. Methods A parent questionnaire was distributed in randomly selected 2 public and 2 private schools from the greater Beirut area during the school year 2017–2018. Questionnaires covered knowledge, attitude (including themes of efficacy, hesitancy and trust), and practice of vaccination in general and influenza vaccine in particular. Results The response rate was 76.5% (306/400). Overall, 29.4% parents reported vaccinating their children against influenza (62.2% in private and 37.7% in public schools). Younger age, paternal employment and higher household income were associated with higher vaccination rates (p = 0.01, 0.02 and <0.0001 respectively). Lack of vaccine recommendation by the physician was the most common reason for not taking it (47%). Parents who accepted influenza vaccination had higher scores in efficacy, hesitancy and trust and were more compliant with other vaccinations. Conclusion One third of parents of school aged children in the greater Beirut area vaccinate their children against influenza. This rate is likely lower in rural remote areas. Physician’s recommendation is the single most important predictor of such vaccination. Future studies tackling physicians’ attitude and practice are needed to help improve influenza vaccination rates in the Lebanese population.
Thoracodorsal Artery Perforator Flap for Chronic Radiation-Induced Ulcer of the Axilla in Vietnam

Breast cancer is the leading cause of death in females worldwide. Radiotherapy plays an important role for locoregional control in the comprehensive management of breast cancer. Chronic radiation-induced ulcer of the axilla can occur, and it is complicated to treat for these lesions. The application of a thoracodorsal artery perforator flap offers many advantages to be one of the most efficient treatments for radiation-induced ulcers of the axillary region. We introduce a series of 5 patients with radiation-induced ulcers of the axilla treated by using a thoracodorsal artery perforator flap. The mean operative time was 190 minutes. During at least a two-year follow-up, no complication has been found, and the patient has achieved good cosmetic result without movement limitation of the upper limb.
Synergistic effects of exosomal crocin or curcumin compounds and HPV L1-E7 polypeptide vaccine construct on tumor eradication in C57BL/6 mouse model

Cervical cancer is the most common malignant tumor in females worldwide. Human papillomavirus (HPV) infection is associated with the occurrence of cervical cancer. Thus, developing an effective and low-cost vaccine against HPV infection, especially in developing countries is an important issue. In this study, a novel HPV L1-E7 fusion multiepitope construct designed by immunoinformatics tools was expressed in bacterial system. HEK-293T cells-derived exosomes were generated and characterized to use as a carrier for crocin and curcumin compounds. The exosomes loaded with crocin and curcumin compounds as a chemotherapeutic agent (ExoCrocin and ExoCurcumin) were used along with the L1-E7 polypeptide for evaluation of immunological and anti-tumor effects in C57BL/6 mouse model. In vitro studies showed that ExoCrocin and ExoCurcumin were not cytotoxic at a certain dose, and they could enter tumor cells. In vivo studies indicated that combination of the L1-E7 polypeptide with ExoCrocin or ExoCurcumin could produce a significant level of immunity directed toward Th1 response and CTL activity. These regimens showed the protective and therapeutic effects against tumor cells (the percentage of tumor-free mice: ~100%). In addition, both ExoCrocin and ExoCurcumin represented similar immunological and anti-tumor effects. Generally, the use of exosomal crocin or curcumin forms along with the L1-E7 polypeptide could significantly induce T-cell immune responses and eradicate tumor cells.