Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Physiological Concentrations of Vitamin C on the Inhibitation of Hydroxyl Radical Induced Light Emission from Fe2+-EGTA-H2O2 and Fe3+-EGTA-H2O2 Systems In Vitro

Ascorbic acid (AA) has antioxidant properties. However, in the presence of Fe2+/Fe3+ ions and H2O2, it may behave as a pro-oxidant by accelerating and enhancing the formation of hydroxyl radicals (•OH). Therefore, in this study we evaluated the effect of AA at concentrations of 1 to 200 µmol/L on •OH-induced light emission (at a pH of 7.4 and temperature of 37 °C) from 92.6 µmol/L Fe2+—185.2 µmol/L EGTA (ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid)—2.6 mmol/L H2O2, and 92.6 µmol/L Fe3+—185.2 µmol/L EGTA—2.6 mmol/L H2O2 systems. Dehydroascorbic acid (DHAA) at the same range of concentrations served as the reference compound. Light emission was measured with multitube luminometer (AutoLumat Plus LB 953) for 120 s after automatic injection of H2O2. AA at concentrations of 1 to 50 µmol/L and of 1 to 75 µmol/L completely inhibited light emission from Fe2+-EGTA-H2O2 and Fe3+-EGTA-H2O2, respectively. Concentrations of 100 and 200 µmol/L did not affect chemiluminescence of Fe3+-EGTA-H2O2 but tended to increase light emission from Fe2+-EGTA-H2O2. DHAA at concentrations of 1 to 100 µmol/L had no effect on chemiluminescence of both systems. These results indicate that AA at physiological concentrations exhibits strong antioxidant activity in the presence of chelated iron and H2O2.
Adding Value in Production of Multifunctional Polylactide (PLA)–ZnO Nanocomposite Films through Alternative Manufacturing Methods

Due to the added value conferred by zinc oxide (ZnO) nanofiller, e.g., UV protection, antibacterial action, gas-barrier properties, poly(lactic acid) (PLA)–ZnO nanocomposites show increased interest for utilization as films, textile fibers, and injection molding items. The study highlights the beneficial effects of premixing ZnO in PLA under given conditions and its use as masterbatch (MB), a very promising alternative manufacturing technique. This approach allows reducing the residence time at high processing temperature of the thermo-sensitive PLA matrix in contact of ZnO nanoparticles known for their aptitude to promote degradation effects onto the polyester chains. Various PLA–ZnO MBs containing high contents of silane-treated ZnO nanoparticles (up to 40 wt.% nanofiller specifically treated with triethoxycaprylylsilane) were produced by melt-compounding using twin-screw extruders. Subsequently, the selected MBs were melt blended with pristine PLA to produce nanocomposite films containing 1–3 wt. % ZnO. By comparison to the more traditional multi-step process, the MB approach allowed the production of nanocomposites (films) having improved processing and enhanced properties: PLA chains displaying higher molecular weights, improved thermal stability, fine nanofiller distribution, and thermo-mechanical characteristic features, while the UV protection was confirmed by UV-vis spectroscopy measurements. The MB alternative is viewed as a promising flexible technique able to open new perspectives to produce more competitive multifunctional PLA–ZnO nanocomposites.
Targeting p53 for Melanoma Treatment: Counteracting Tumour Proliferation, Dissemination and Therapeutic Resistance

Simple Summary Melanoma is a highly metastatic and therapy-resistant cancer and is therefore associated with low survival rates of patients. In melanoma, the inactivation of the wild-type form of the p53 tumour suppressor protein is a frequent event, mainly through interactions with MDM2 and MDMX. In this work, our recently disclosed p53-activating agent, SLMP53-2, displayed promising in vitro and in vivo antitumour activity, with particular impacts on melanoma migration and invasion. Moreover, SLMP53-2 (re)sensitized melanoma cells to clinically used chemotherapeutic agents, potentially overcoming the therapeutic resistance issue. As a whole, the p53 activator SLMP53-2 may represent a new therapeutic opportunity for melanoma, particularly in combination with MAPK pathway-targeting drugs. Abstract Melanoma is the deadliest form of skin cancer, primarily due to its high metastatic propensity and therapeutic resistance in advanced stages. The frequent inactivation of the p53 tumour suppressor protein in melanomagenesis may predict promising outcomes for p53 activators in melanoma therapy. Herein, we aimed to investigate the antitumor potential of the p53-activating agent SLMP53-2 against melanoma. Two- and three-dimensional cell cultures and xenograft mouse models were used to unveil the antitumor activity and the underlying molecular mechanism of SLMP53-2 in melanoma. SLMP53-2 inhibited the growth of human melanoma cells in a p53-dependent manner through induction of cell cycle arrest and apoptosis. Notably, SLMP53-2 induced p53 stabilization by disrupting the p53–MDM2 interaction, enhancing p53 transcriptional activity. It also promoted the expression of p53-regulated microRNAs (miRNAs), including miR-145 and miR-23a. Moreover, it displayed anti-invasive and antimigratory properties in melanoma cells by inhibiting the epithelial-to-mesenchymal transition (EMT), angiogenesis and extracellular lactate production. Importantly, SLMP53-2 did not induce resistance in melanoma cells. Additionally, it synergized with vemurafenib, dacarbazine and cisplatin, and resensitized vemurafenib-resistant cells. SLMP53-2 also exhibited antitumor activity in human melanoma xenograft mouse models by repressing cell proliferation and EMT while stimulating apoptosis. This work discloses the p53-activating agent SLMP53-2 which has promising therapeutic potential in advanced melanoma, either as a single agent or in combination therapy. By targeting p53, SLMP53-2 may counteract major features of melanoma aggressiveness.
Effects of Epstein-Barr Virus Infection on the Risk and Prognosis of Primary Laryngeal Squamous Cell Carcinoma: A Hospital-Based Case-Control Study in Taiwan

Simple Summary Epstein–Barr virus DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression were identified as independent risk factors for primary laryngeal squamous cell carcinoma. A high EBER signal and low CD3 expression significantly and independently predicted local recurrence and disease-free survival within five years. The information obtained in this study improves our understanding of viral infections in laryngeal cancer, and may guide future prevention, treatment, and follow-up strategies. Abstract Mounting molecular evidence supports Epstein–Barr virus (EBV) involvement in the pathogenesis of laryngeal squamous cell carcinoma (LSCC); however, the epidemiological data are inconsistent. In this retrospective case-control study, we aimed to determine whether EBV infection underlies the risk and prognosis of LSCC. The prevalence of EBV infection, as analyzed using an EBV DNA polymerase chain reaction assay, was significantly higher in 42 Taiwanese patients with newly diagnosed primary LSCC, compared to 39 age- and sex-matched control patients without cancer (48% vs. 19%). Furthermore, most of the EBER signals detected using in situ hybridization were localized to the nuclei of tumor-infiltrating lymphocytes. In multivariate analysis, EBV DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression (assessed using immunohistochemistry) were identified as independent risk factors for LSCC. Furthermore, five-year local recurrence and disease-free survival rates were 34% and 58%, respectively, with a high EBER signal and low CD3 expression independently predicting five-year local recurrence and disease-free survival. Our comprehensive profiling data accurately identified patients at risk for LSCC development, local recurrence, or disease-free survival. The information obtained in this study improves our understanding of EBV infection in LSCC, and may guide precision medicine for patients with LSCC.
Anticancer Potential of Betulonic Acid Derivatives

Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.
A Pixel Design of a Branching Ultra-Highspeed Image Sensor

A burst image sensor named Hanabi, meaning fireworks in Japanese, includes a branching CCD and multiple CMOS readout circuits. The sensor is backside-illuminated with a light/charge guide pipe to minimize the temporal resolution by suppressing the horizontal motion of signal carriers. On the front side, the pixel has a guide gate at the center, branching to six first-branching gates, each bifurcating to second-branching gates, and finally connected to 12 (=6×2) floating diffusions. The signals are either read out after an image capture operation to replay 12 to 48 consecutive images, or continuously transferred to a memory chip stacked on the front side of the sensor chip and converted to digital signals. A CCD burst image sensor enables a noiseless signal transfer from a photodiode to the in-situ storage even at very high frame rates. However, the pixel count conflicts with the frame count due to the large pixel size for the relatively large in-pixel CCD memory elements. A CMOS burst image sensor can use small trench-type capacitors for memory elements, instead of CCD channels. However, the transfer noise from a floating diffusion to the memory element increases in proportion to the square root of the frame rate. The Hanabi chip overcomes the compromise between these pros and cons.
Radiation on Earth or in Space: What Does It Change?

After having been an instrument of the Cold War, space exploration has become a major technological, scientific and societal challenge for a number of countries. With new projects to return to the Moon and go to Mars, radiobiologists have been called upon to better assess the risks linked to exposure to radiation emitted from space (IRS), one of the major hazards for astronauts. To this aim, a major task is to identify the specificities of the different sources of IRS that concern astronauts. By considering the probabilities of the impact of IRS against spacecraft shielding, three conclusions can be drawn: (1) The impacts of heavy ions are rare and their contribution to radiation dose may be low during low Earth orbit; (2) secondary particles, including neutrons emitted at low energy from the spacecraft shielding, may be common in deep space and may preferentially target surface tissues such as the eyes and skin; (3) a “bath of radiation” composed of residual rays and fast neutrons inside the spacecraft may present a concern for deep tissues such as bones and the cardiovascular system. Hence, skin melanoma, cataracts, loss of bone mass, and aging of the cardiovascular system are possible, dependent on the dose, dose-rate, and individual factors. This suggests that both radiosusceptibility and radiodegeneration may be concerns related to space exploration. In addition, in the particular case of extreme solar events, radiosensitivity reactions—such as those observed in acute radiation syndrome—may occur and affect blood composition, gastrointestinal and neurologic systems. This review summarizes the specificities of space radiobiology and opens the debate as regards refinements of current radiation protection concepts that will be useful for the better estimation of risks.
A NOVEL APPROACH TO INCREASE THE BIOAVAILABILITY OF CANDESARTAN CILEXETIL BY PRONIOSOMAL GEL FORMULATION: IN-VITRO AND IN-VIVO EVALUATION

Objective: The oral bioavailability of Candesartan cilexetil is less (<15%), so in this study an approach has been made to increase its bioavailability by proniosomal gel formulation. Methods: The proniosomal formulation of Candesartan cilexetil was prepared by slurry method, using span 60 and Tween 60 as non-ionic surfactants, maltodextrin as carrier and cholesterol and soya lecithin as stabilizers. Prepared gel formulations were evaluated for compatibility study, entrapment efficiency, vesicle size, surface morphology, in-vitro diffusion studies, in-vitro skin permeation studies , in-vivo pharmacokinetics studies, various release kinetic studies and stability studies. Results: FT-IR study showed no interaction between drugs and other excipients, drugs and excipients are compatible. Mean vesicles size of proniosome derived niosome was found in the range of 16.34 µm-32.48 µm and 7.25-16.45 µm before and after shaking. An optimized formulation A 3 containing a 2:1 ratio of span 60 and cholesterol showed maximum entrapment (86.17%) and in-vitro drug release (93.8%) compared to other formulations. In-vitro skin permeation studies were carried out using Albino rat skin and results showed that formulation A 3 exhibited 88.65% drug permeation in a steady-state manner over a period of 24 h with a flux value of 1.94 µg/cm 2 /h and enhancement ratio of 3.73. In-vivo pharmacokinetics studies of proniosomal gel formulation A 3 showed a significant increase in bioavailability (1.425 folds) compared with an oral formulation of Candesartan cilexetil. Stability studies showed that proniosomal gel formulation was stable throughout its study period. Conclusion: Physiochemically stable Candesartan cilexetil proniosomal gel was formulated, which could deliver significant amount of the drug across the skin in a steady-state manner for the prolong period of time in the treatment of hypertension.
Inhibitors of Protein Convertase Subtilisin/Kexin 9 (PCSK9) and Acute Coronary Syndrome (ACS): The State-of-the-Art

Acute Coronary Syndrome (ACS) remains one of the most frequent causes of morbidity and mortality in the world. Although the age- and gender-adjusted incidence of ACS is decreasing, the mortality associated with this condition remains high, especially 1-year after the acute event. Several studies demonstrated that PCSK9 inhibitors therapy determine a significant reduction of major adverse cardiovascular events (MACE) in post-ACS patients, through a process of plaque modification, by intervening in lipid metabolism and platelet aggregation and finally determining an improvement in endothelial function. In the EVACS (Evolocumab in Acute Coronary Syndrome) study, evolocumab allows >90% of patients to achieve LDL-C < 55 mg/dL according to ESC/EAS guidelines compared to 11% of patients who only receive statins. In the EVOPACS (EVOlocumab for Early Reduction of low-density lipoprotein (LDL)-cholesterol Levels in Patients With Acute Coronary Syndromes) study, evolocumab determined LDL levels reduction of 40.7% (95% CI: 45.2 to 36.2; p < 0.001) and allowed 95.7% of patients to achieve LDL levels <55 mg/dL. In ODYSSEY Outcome trial, alirocumab reduced the overall risk of MACE by 15% (HR = 0.85; CI: 0.78–0.93; p = 0.0003), with a reduced risk of all-cause mortality (HR = 0.85; CI: 0.73–0.98: nominal p = 0026), and fewer deaths for coronary heart disease (CHD) compared to the control group (HR = 0.92; CI: 0.76–1.11; p = 0.38). The present review aimed at describing the beneficial effect of PCSK9 inhibitors therapy early after ACS in reducing LDL circulating levels (LDL-C) and the risk of major adverse cardiovascular events, which was very high in the first year and persists higher later after the acute event.
Left Atrial Appendage Closure with a New Occluder Device: Efficacy, Safety and Mid-Term Performance

The LAmbreTM device is a novel system designed for left atrial appendage closure (LAAC). First registries showed a high rate of device implantation success. However, few mid-term results are available. We present our 1- and 12-month follow-up results for this device. This prospective, single-center registry included consecutive patients with nonvalvular atrial fibrillation who underwent LAAC with the LAmbreTM device. Transesophageal echocardiography (TEE) was performed at 1-month follow-up. In total, 55 patients were included. The population was elderly (75 ± 9.4 years), with a high proportion of comorbidities. The mean CHA2DS2-VASc and HAS-BLED scores were 4.6 ± 1.6 and 3.9 ± 1.0, respectively. Previous history of a major bleeding event was present in 37 patients (67.3%). Procedural success was achieved in 54 patients (98.2%). Device success was achieved in 100% of patients in whom device implantation was attempted (54 patients). Major in-hospital device-related complications included mortality of one patient (1.8%) and pericardial tamponade in two patients (3.6%); the incidence of stroke was 0%. No thrombus or significant leaks (≥5 mm) were observed on 1-month TEE. At 12 months, adverse events were overall death (1.8%), transient ischemic attack/ischemic stroke (1.8%), and major bleeding events (Bleeding Academic Research Consortium (BARC) 3a and 3c; 11%). In this high-risk population, the LAmbreTM device seems to be a safe and effective option for LAAC with a remarkable mid-term performance.
Physical Exercise and Health-Related Quality of Life in Office Workers: A Systematic Review and Meta-Analysis

Office workers are at high risk for many chronic diseases, lowering their health-related quality of life (HRQOL). This systematic review and meta-analysis aimed to summarize the effects of physical exercise on HRQOL in office workers with and without health problems using data obtained from randomized controlled trials (RCTs), quasi-experimental, and observational studies. We searched PubMed, Web of Science, Scopus, Cochrane Library, and several grey literature databases, and identified 26 relevant studies for the synthesis. Overall, physical exercise significantly improved general (standardized mean difference (SMD) = 1.05; 95% confidence interval (CI): 0.66 to 1.44) and mental (SMD = 0.42; 95% CI: 0.19 to 0.66) HRQOL in office workers. Compared with healthy office workers, unhealthy office workers experienced greater improvements in general (unhealthy, SMD = 2.76; 95% CI: 1.63 to 3.89; healthy, SMD = 0.23; 95% CI: −0.09 to 0.56) and physical (unhealthy, SMD = 0.38; 95% CI: 0.17 to 0.58; healthy, SMD = −0.20; 95% CI: −0.51 to 0.11) HRQOL. Unsupervised physical exercise significantly improved general and mental HRQOL, while directly supervised physical exercise significantly improved only general HRQOL. Although physical exercise, especially unsupervised physical exercise, should be encouraged to improve HRQOL in office workers, detailed recommendations could not be made because of the diverse exercise types with different intensities. Therefore, further studies are needed to determine the optimal exercise for office workers with different health conditions.
Memetic Chains for Improving the Local Wireless Sensor Networks Localization in Urban Scenarios †

Local Positioning Systems (LPS) have become an active field of research in the last few years. Their application in harsh environments for high-demanded accuracy applications is allowing the development of technological activities such as autonomous navigation, indoor localization, or low-level flights in restricted environments. LPS consists of ad-hoc deployments of sensors which meets the design requirements of each activity. Among LPS, those based on temporal measurements are attracting higher interest due to their trade-off among accuracy, robustness, availability, and costs. The Time Difference of Arrival (TDOA) is extended in the literature for LPS applications and consequently we perform, in this paper, an analysis of the optimal sensor deployment of this architecture for achieving practical results. This is known as the Node Location Problem (NLP) and has been categorized as NP-Hard. Therefore, heuristic solutions such as Genetic Algorithms (GA) or Memetic Algorithms (MA) have been applied in the literature for the NLP. In this paper, we introduce an adaptation of the so-called MA-Solis Wets-Chains (MA-SW-Chains) for its application in the large-scale discrete discontinuous optimization of the NLP in urban scenarios. Our proposed algorithm MA-Variable Neighborhood Descent-Chains (MA-VND-Chains) outperforms the GA and the MA of previous proposals for the NLP, improving the accuracy achieved by 17% and by 10% respectively for the TDOA architecture in the urban scenario introduced.
Qualitative Assessment of Effective Gamification Design Processes Using Motivators to Identify Game Mechanics

This research focuses on the study and qualitative assessment of the relationships between motivators and game mechanics per the ratings of expert gamification consultants. By taking this approach, it is intended that during the design phase of a gamified system, decisions can be made about the design of the system based on the motivators of each of the profiles. These motivators can be determined from the information provided by the potential players themselves. The research presented starts from a previous analysis in which, based on the three most used gamification frameworks and through a card sorting technique that allows the user to organize and classify the content, a set of mechanics are determined. In the present study, each of the mechanics is analyzed, and a more precise motive is decided. As a result, a higher level of personalization is achieved and, consequently, approximates a higher level of gamification effectiveness. The main conclusions are implemented in the development of the Game4City 3.0 project, which addresses gamified and interactive strategies to visualize urban environments in 3D at an educational and social level.
CHOP Pro-Apoptotic Transcriptional Program in Response to ER Stress Is Hacked by Zika Virus

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus considered as a threat to human health due to large epidemics and serious clinical outcomes such as microcephaly in new-borns. Like all flaviviruses, ZIKV relies on the cellular machinery to complete its viral cycle, with the endoplasmic reticulum (ER) being the critical site of viral replication factories. The sudden high protein load in the ER induces an ER stress to which the cell responds with an appropriate unfolded protein response (UPR) in an attempt to restore its disturbed homeostasis. When the restoration fails, the cell signalling leads to a programmed cell death by apoptosis with the upregulation of the UPR-induced C/EBP homologous protein (CHOP) which acts as the main trigger for this fatal outcome. Our previous studies have shown the ability of ZIKV to manipulate various cellular responses in order to optimize virus production. ZIKV is able to delay apoptosis to its benefit and although ER stress is induced, the UPR is not complete. Here we discovered that ZIKV impairs the expression of CHOP/DDIT3, the main factor responsible of ER-stress driven apoptosis. Surprisingly, the mechanism does not take place at the transcriptional level but at the translational level.