Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene Therapy: Potential Applications of Nanotechnology

Gene therapy is emerging as a new class of therapeutics for the treatment of inherited and acquired diseases. However, poor cellular uptake and instability of DNA in the physiological milieu limits its therapeutic potential, hence a vector which can protect and efficiently transport DNA to the target cells must be developed. Nanotechnology-based non-viral vectors have been proposed as potential candidates. Various polymeric nanoparticles have been shown to be suitable, with high cellular uptake efficiencies and reduced cytotoxicity. These delivery vectors form condensed complexes with DNA which result in shielding against enzymatic degradation and enhanced cellular targeting. Advantages including easy manipulatibility, high stability, low cost and high payload, mean that nanoparticles from various polymers have been exploited. Gene therapy gives a systematic account of the many aspects of nanotechnology mediated gene therapy, from the preparation of nanoparticles to physicochemical characterization, and follows with applications in in vitro and in vivo models. This book emphasizes the various aspects of nanotechnology-based gene therapy, with initial chapters detailing the tools and techniques available for preparation and in vitro and in vivo characterization of nanoparticles. Later chapters provide exhaustive details on polymeric systems employed for gene therapy.Provides an overview of nanotechnology applications in gene therapy, from preparation of nanoparticles to in vitro and in vivo studiesDetails the tools and techniques available for preparation, characterization and in vitro and in vivo study of nanoparticlesDetails the limitations of nanoparticle-mediated gene therapy and proposes ways in which they may be overcome
An exploratory study of organizational cyber resilience, its precursors and outcomes

ABSTRACT Evidence shows that it is paramount for stakeholders to understand the cybersecurity of relevant organizations. However, the secrecy surrounding cyber attacks and how organizations manage their cyber resilience make it impossible for stakeholders to develop this understanding. This paper analyzes organizational cyber resilience, its contextual factors and its impact on the outcomes of cyber attacks based on publicly available data. Using the PRISMA methodology, we collated and analyzed a dataset of 1,145 publicly known cyber attacks. We conceptualize and operationalize cyber resilience from a governance perspective. Our findings indicate that organizations that suffered cyber attacks had the following cyber resilience characteristics: a relatively low level of cyber resilience reflected in the low frequency of cybersecurity roles, low reliance on cybersecurity frameworks, and relatively low strength of prevention, detection, and recovery controls. Cyber resilience is found to be associated with the sector, size, and digital intensity. Linear regression indicates that, expectedly, stronger prevention, detection, and recovery processes are related to lower breach severity and occurrence of investigations or penalties, but contrary to expectations, cybersecurity roles and frameworks are not. Furthermore, better organizational responses are associated with higher breach severity but they are not found to have an impact on the level of investigations, fines, and penalties imposed. We discuss our findings and their implications for cyber resilience regulation, future research, and sector cooperation.
Inhibition of Nucleation Using a Dilute, Weakly Hydrogen-Bonding Molecular Additive

The effect of a weakly interacting dilute complexing agent on the nucleation rates of a small-molecule solute was explored using the model system of 3-nitrophenol as the inhibited molecule in a toluene solution with a 3-aminobenzoic acid inhibitor. Induction times were measured experimentally using the probability distribution of the solute crystals nucleation events as a function of time. Experimental results demonstrated that a small concentration of inhibitor (0.25% molar with respect to solute) led to a 230% increase in induction times with respect to noninhibited controls at identical supersaturation. Product crystal growth rates, polymorphism, and purity were found to be unaffected by the complexing agent, confirming that the change in nucleation rate was only due to nucleation inhibition. The nucleation rate kinetics of the solute were studied as a function of supersaturation, with and without the inhibitor. Data indicated that upon the addition of the inhibitor, there is a sharp decrease in the pr.
Weekly versus triweekly cisplatin-based concurrent chemoradiotherapy for nasopharyngeal carcinoma: a systematic review and pooled analysis

Background: Weekly and triweekly cisplatin-based concurrent chemoradiotherapy (CCRT) have been used in the treatment of nasopharyngeal carcinoma (NPC). Objective: This study aimed to compare the benefits and risks between the two treatments. Methods: We systematically searched electronic databases for prospective and retrospective clinical studies of NPC patients who received weekly compared with triweekly cisplatin-based CCRT. The primary endpoints comprised overall, failure-free, distant metastasis-free, and locoregional recurrence-free survivals (OS, FFS, DMFS, and LRFS). Secondary endpoints were toxicities. Results: Six studies were included in the systematic review, of which four with 1515 NPC patients were eligible for further pooled analysis. There were no significant differences between weekly and triweekly groups in terms of 5-year OS (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.51-1.79), FFS (OR 1.09, 95% CI 0.67-1.76), DMFS (OR 1.25, 95% CI 0.54-2.92), and LRFS (OR 0.83, 95% CI 0.55-1.25). For grade ≥ 3 toxicities, the weekly group had higher risks of anemia (risk ratio [RR] 2.96, 95% CI 1.12-7.81) and thrombocytopenia (RR 2.75, 95% CI 1.54-4.90), but a lower incidence of vomiting (RR 0.34, 95% CI 0.18-0.63) versus the triweekly group. Conclusion and Relevance: Both weekly and triweekly schedules could be recommended to NPC patients during CCRT. Additionally, hematologic adverse events in weekly strategy and non-hematologic adverse events in triweekly strategy are of higher concern.
The regulatory networks of the Hippo signaling pathway in cancer development

The Hippo signaling pathway is a relatively young tumor-related signaling pathway. Although it was discovered lately, research on it developed rapidly. The Hippo signaling pathway is closely relevant to the occurrence and development of tumors and the maintenance of organ size and other biological processes. This manuscript focuses on YAP, the core molecule of the Hippo signaling pathway, and discussion the upstream and downstream regulatory networks of the Hippo signaling pathway during tumorigenesis and development. It also summarizes the relevant drugs involved in this signaling pathway, which may be helpful to the development of targeted drugs for cancer therapy.
Late-onset Leigh syndrome without delayed development in China: A case report

BACKGROUND Leigh syndrome (LS) is one of the most common mitochondrial diseases in infants and children. LS often manifests as early-onset with delayed phenotypic development. However, late-onset LS with normal development and white matter lesions in the brain is rarely reported, thereby highlighting the phenotypic variability of LS expression. CASE SUMMARY We report a 12-year-old boy who presented with an unusual late-onset and fulminant form of LS that is maternally inherited without developmental delay. The patient was admitted to the hospital with symptoms of ptosis and somnolence, and died within 2 mo. Analysis of peripheral blood leukocytes showed a homoplasmic m.9176T>C mutation in the patient. Magnetic resonance imaging also revealed lesions in bilateral white matter as well as symmetrical lesions in the basal ganglia and brain stem. The patient was diagnosed with LS. The patient was treated with vitamin C, vitamin D, and adenosine-triphosphate. The patient died within 2 mo of hospital admission. CONCLUSION LS can present in both infants and older children with different phenotypes.
Genetic differentiation of mainland-island sheep of Greece: Implications for identifying candidate genes for long-term local adaptation

In Greece, a number of local sheep breeds are raised in a wide range of ecological niches across the country. These breeds can be used for the identification of genetic variants that contribute to local adaptation. To this end, 50k genotypes of 90 local sheep from mainland Greece (Epirus, n = 35 and Peloponnesus, n = 55) were used, as well as 147 genotypes of sheep from insular Greece (Skyros, n = 21), Lemnos, n = 36 and Lesvos, n = 90). Principal components and phylogenetic analysis along with admixture and spatial point patterns analyses suggested genetic differentiation of ‘mainland-island’ populations. Genome scans for signatures of selection and genome-wide association analysis (GWAS) pointed to one highly differentiating marker on OAR4 (FST = 0.39, FLK = 21.93, FDR p-value = 0.10) that also displayed genome wide significance (FDR p-value = 0.002) during GWAS. A total number of 6 positional candidate genes (LOC106990429, ZNF804B, TEX47, STEAP4, SRI and ADAM22) were identified within 500 kb flanking regions around the significant marker. In addition, two QTLs related to fat tail deposition are reported in genomic regions 800 kb downstream the significant marker. Based on gene ontology analysis and literature evidence, the identified candidate genes possess biological functions relevant to local adaptation that worth further investigation.
Bioactive Hexapeptide Reduced the Resistance of Ovarian Cancer Cells to DDP by Affecting HSF1/HSP70 Signaling Pathway

Ovarian cancer is the leading cause of death in gynecologic malignancies. Ovarian cancer as a metastatic malignant tumor is highly recurrent and prone to drug resistance. Bioactive peptides are an emerging area of biomedical research in reducing resistance of tumor cell to drugs. In this paper, we investigated the effects and mechanisms of bioactive hexapeptide (PGPIPN) derived in milk protein on the sensitivity of ovarian cancer cells to cis-dichlorodiammine platinum (DDP). Human ovarian cancer cell lines (SKOV3 and COC1), their DDP-resistant sublines (SKOV3/DDP and COC1/DDP) and human primary ovarian cancer cells were cultured in vitro under the combined treatment of DDP (close to IC50) and different concentrations of PGPIPN. The viabilities, apoptosis and cell cycle changes were respectively measured by WST-8 and flow cytometry. The mRNA and protein expression levels of HSF1, HSP70, MDR1, ERCC1 and β-actin gene were respectively assayed by RT-qPCR and western blotting. The results showed that PGPIPN significantly increased the sensitivity of human ovarian cancer cells to DDP in inhibiting viability and inducing apoptosis in vitro. But the effects in sensitive cells were lower than DDP-resistant cells. PGPIPN significantly changed the cell cycles in all human ovarian cancer cells, which leaded to a significant increase in the percentage of cells blocked at G2/M phase and decrease the percentage of cells at G1 phases in a dose-dependent manner. PGPIPN affected the expression levels of HSF1, HSP70, MDR1 and ERCC1 genes. Compared with cells in DDP treatment alone, the expression levels of HSF1 and HSP70 in human ovarian cancer cells treated with DDP and PGPIPN together significantly decreased in dose-dependent manner. PGPIPN significantly decreased MDR1 and ERCC1 of drug-resistant ovarian cancer cell lines and human primary ovarian cancer cell in a dose-dependent manner. Pifithrin-μ (PFTμ, HSP70 inhibitor) decreased or removed the effects of peptide in increasing the sensitivity of ovarian cancer cells to DDP. This suggests that PGPIPN enhanced the sensitivity of ovarian cancer cells to DDP partially via reducing the activity of HSF1/HSP70 signaling pathway, thus inducing cell apoptosis and decreasing repairment of DNA damage.
Evaluation of the visibility of peri-implant bone defects using ultrasonography with two types of probes

Abstract Background: The aim of the present study was to evaluate the efficacy of intraoral and extraoral ultrasonography evaluations performed with two different types of probes (linear and “hockey stick”) for the visibility of peri-implant bone defects. Material and methods: Fourteen implants were inserted into sheep heads. Peri-implant bone defects were created without knowing the depth, which served as the gold standard for the defects. The defects were scanned with two different probe types (linear and hockey stick probes) extraorally and intraorally, using two different ultrasonography systems. For intra- and interobserver agreements for each probe types, Kappa coefficients were calculated. Results: The lowest ICC values were found in both intra- (ICC = 0.696) and interobserver reliability (ICC = 0.762) obtained with the extraorally used linear probe. There was a high agreement with the gold standard when using hockey sticky probes intraorally. For both linear probes, there were no significant differences in agreement among the two observers and the gold standard (p >0.05). Conclusions: High agreement was found when using high-frequency hockey stick probes intraorally, which means that they can be used with good effect for the evaluation of the visibility of peri-implant bone defects. To the best of our knowledge, this study is the first one on this subject. Thus, it can be stated that US can be an alternative method of examining defects. However, further studies are needed to evaluate the effectiveness of US in visualizing peri-implant bone defects.
Novel model combining contrast-enhanced ultrasound with serology predicts hepatocellular carcinoma recurrence after hepatectomy

BACKGROUND Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). However, recurrence within 2 years is observed in 30%–50% of patients, being a major cause of mortality. AIM To construct and verify a non-invasive prediction model combining contrast-enhanced ultrasound (CEUS) with serology biomarkers to predict the early recurrence of HCC. METHODS Records of 744 consecutive patients undergoing first-line curative surgery for HCC in one institution from 2016–2018 were reviewed, and 292 local patients were selected for analysis. General characteristics including gender and age, CEUS liver imaging reporting and data system (LIRADS) parameters including wash-in time, wash-in type, wash-out time, and wash-out type, and serology biomarkers including alanine aminotransferase, aspartate aminotransferase, platelets, and alpha-fetoprotein (AFP) were collected. Univariate analysis and multivariate Cox proportional hazards regression model were used to evaluate the independent prognostic factors for tumor recurrence. Then a nomogram called CEUS model was constructed. The CEUS model was then used to predict recurrence at 6 mo, 12 mo, and 24 mo, the cut-off value was calculate by X-tile, and each C-index was calculated. Then Kaplan-Meier curve was compared by log-rank test. The calibration curves of each time were depicted. RESULTS A nomogram predicting early recurrence (ER), named CEUS model, was formulated based on the results of the multivariate Cox regression analysis. This nomogram incorporated tumor diameter, preoperative AFP level, and LIRADS, and the hazard ratio was 1.123 (95% confidence interval [CI]: 1.041-1.211), 1.547 (95%CI: 1.245-1.922), and 1.428 (95%CI: 1.059-1.925), respectively. The cut-off value at 6 mo, 12 mo, and 24 mo was 100, 80, and 50, and the C-index was 0.748 (95%CI: 0.683-0.813), 0.762 (95%CI: 0.704-0.820), and 0.762 (95%CI: 0.706-0.819), respectively. The model showed satisfactory results, and the calibration at 6 mo was desirable; however, the calibration at 12 and 24 mo should be improved. CONCLUSION The CEUS model enables the well-calibrated individualized prediction of ER before surgery and may represent a novel tool for biomarker research and individual counseling.
Lower p66Shc promoter methylation in subjects with chronic renal failure

Objective To determine the correlation between DNA methylation of p66Shc promoter and some markers of inflammatory and oxidative stress in chronic renal failure (CRF) patients compared with healthy subjects. Methods An observational cross-sectional study was conducted in the nephrology department at Sidi Bouzid Regional Hospital (Tunisia). In total, 39 patients with CRF and 37 healthy subjects were included. Several biochemical parameters were measured. Furthermore, markers of the oxidative and inflammatory status (MDA, TAS, SOD, and CRP) were evaluated. The p66Shc methylation status was determined using the methylation-specific PCR. Results Our results showed that levels of blood glucose, urea, creatinine, uric acid, ChT, TG, albuminuria, CRP and MDA were significantly elevated in CRF patients compared to controls. Furthermore, p66Shc promoter region was highly demethylated in CRF patients compared to healthy controls (84% vs 4%). Our data showed a positive correlation between p66Shc hypomethylation and levels of MDA (r = 0.93; p<0, 05) and CRP (r = 0.89; P <0, 05), as well as a significant negative correlation between p66Shc hypomethylation, TAS (r = -0.76; P <0, 05) and SOD (r = -0.77; p<0, 05) levels. Similarly, there was a positive correlation between p66Shc hypomethylation and the disease stages. Importantly, multiple regression analysis showed that p66shc DNA hypomethylation remains strongly correlated with MDA, CRP and stages of CRF. Conclusion This study indicates that the DNA hypomethylation of p66shc promoter was correlated with oxidative and inflammatory stress and the disease stages in CRF patients.
Structural analysis of the GPI glycan

Glycosylphosphatidylinositol (GPI) anchoring of proteins is an essential post-translational modification in all eukaryotes that occurs at the endoplasmic reticulum (ER) and serves to deliver GPI-anchored proteins (GPI-APs) to the cell surface where they play a wide variety of vital physiological roles. This paper describes a specialized method for purification and structural analysis of the GPI glycan of individual GPI-APs in yeast. The protocol involves the expression of a specific GPI-AP tagged with GFP, enzymatic release from the cellular membrane fraction, immunopurification, separation by electrophoresis and analysis of the peptides bearing GPI glycans by mass spectrometry after trypsin digestion. We used specifically this protocol to address the structural remodeling that undergoes the GPI glycan of a specific GPI-AP during its transport to the cell surface. This method can be also applied to investigate the GPI-AP biosynthetic pathway and to directly confirm predicted GPI-anchoring of individual proteins.
Masticatory Ability for a Single Implant Mandibular Overdenture Retained by Two Different Attachments: A Randomized Controlled Trial

Objective The aim of this randomized clinical trial was to compare the masticatory ability subjectively between ball and Cendres+Métaux Locator (CM-LOC) attachment for a single implant retained mandibular overdenture throughout a 24-month follow-up period. Materials and Methods Eighty completely edentulous patients were recruited. All patients received new complete dentures, and masticatory ability was recorded using a questionnaire (baseline record). All patients received a single implant in the midline of the completely edentulous mandible. After 3-month healing period, patients were randomized using sealed envelopes into two groups: ball or CM-LOC attachment. The same masticatory ability questionnaire was used to record masticatory ability for both groups after 2 weeks of pickup and 3-, 6-, 9-, 12-, and 24-month follow-up. Comparison between the study groups was done using Mann–Whitney U test for independent samples. Two-sided P values less than 0.05 were considered statistically significant. Results The mean masticatory scores improved for both attachments, with no statistically significant difference between them throughout the 24-month follow-up. The CM-LOC attachment group showed a greater improvement change in masticatory ability after 6- and 12-month follow-up (−12.47 ± 12.006, −11.46 ± 14.625; P=0.826), while the ball attachment group showed a slight improvement after the 24-month follow-up (−11.72 ± 12.368, −10.88 ± 11.963; P=0.778). Conclusion Single implant retained mandibular overdenture improved masticatory ability subjectively with no significant difference between both attachments used although the ball attachment showed better masticatory ability scores after 24-month follow-up.
The Importance of miRNA Identification During Respiratory Viral Infections

The expression of small non-coding RNA MicroRNAs (miRNAs) during respiratory viral infections is of critical importance as they are implicated in the viral replication, immune responses and severity of disease pathogenesis. Respiratory viral infections have an extensive impact on human health across the globe. For that is essential to understand the factors that regulate the host response against infections. The differential miRNA pattern induced by respiratory viruses has been reported, including include influenza A virus (IAV), human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), adenovirus (AdV), and more recently, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. In this commentary, we highlight the importance of miRNAs identification and the contribution of these molecules in the modulation of the immune response through the upregulation and downregulation of miRNAs expression in different immune and non-immune cells.
Screening of potential tropical fruits in protecting endothelial dysfunction in vitro

Background High consumption of antioxidant-rich fruits and vegetables reduces the endothelial damage involved in cardiovascular disease pathogenesis. Objective To evaluate the phytochemical content, antioxidant and scavenging activities (FRAP, ORAC, OH•, HOCl, H2O2, and O2−), endothelial H2O2-cytoprotective effect, nitric oxide (NO) release activation potential, and endothelial wound healing properties of 10 tropical fruits, comprising pineapple, sugar apple, papaya fruit, longan, mangosteen, lychee, langsat, mango, rambutan, and guava. Design Experimental study. The experiments were conducted in vitro using endothelial cell line EA.hy926. Results The high performance liquid chromatography (HPLC) phytochemical analysis indicated the presence of gallic acid and quercetin in all fruits, along with the overall absence of ellagic acid. Chlorogenic acid was only detected in three fruits, that is, pineapple, ripe papaya, and guava. The antioxidant and scavenging activities of all fruits were concentration-dependent. Only the H2O2 scavenging activity exhibited broad positive associations with other ROS-scavenging activities. Sugar apple and unripe papaya induced a significant reduction in H2O2-induced cell death in endothelial cells while pineapple, sugar apple, longan, and langsat activated NO release. Discussion All the studied tropical fruits contained bioactive phytoantioxidants with wide ranges of antioxidant capacity and scavenging activities. The endothelial functional tests were relevant to the screening for fruits that may benefit cardiovascular health. Among the four fruits that promoted endothelial wound closure, only sugar apple and unripe papaya induced cell migration and vascular capillary-like tube formation. Conclusion Sugar apple and unripe papaya are potential functional fruits that can protect against oxidative cell death and enhance endothelial wound healing.