Miracle-dz/UniFAR-FTUs huggingface dataset:
The Overall Efficacy and Outcomes of Metronomic Tegafur-Uracil Chemotherapy on Locally Advanced Head and Neck Squamous Cell Carcinoma: A Real-World Cohort Experience

Simple Summary In head and neck squamous cell carcinoma (HNSCC), more than 60% of patients presenting with locally advanced disease carries a high risk of recurrence and distant metastasis, with a poor prognosis (five-year overall survival (OS), <50%). Therefore, further prevention of recurrence and distant metastasis is crucial for survival improvement in advanced HNSCC patients. In this retrospective study, we investigated the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced HNSCC (LA HNSCC). Our data showed that adding tegafur–uracil after curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved OS, DFS, and DMFS in patients with LA HNSCC. As a metronomic maintenance regimen, tegafur–uracil was well tolerated with minimal adverse effects. We suggested tegafur–uracil as a maintenance therapy of choice for patients with LA HNSCC. Abstract Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aimed to demonstrate the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced head and neck squamous cell carcinoma (LA HNSCC). This was a retrospective study including 240 patients with LA HNSCC. After standard treatment, 96 patients were further treated with metronomic tegafur-uracil, and 144 patients were not. No statistical differences were found between both groups with regard to sex, clinical stage, or primary treatment choice. There were more hypopharyngeal cancers and more patients with poor clinicopathological features, including lymphovascular invasion, extranodal extension, and positive margins in the tegafur–uracil group. The median follow-up duration was 31.16 months. Overall survival (OS) was not reached in the tegafur–uracil group and was 54.1 months in the control group (p = 0.008). The median disease-free survival (DFS) was 54.5 months in the tegafur–uracil group and 34.4 months in the control group (p = 0.03). Neither group reached distant metastasis-free survival (DMFS, p = 0.02). In patients with LA HNSCC, adding tegafur–uracil as metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved the OS, DFS, and DMFS with tolerable adverse events.
The Antiobesity Effect of GLP-1 Receptor Agonists Alone or in Combination with Metformin in Overweight /Obese Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Objectives Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin (MET) have markedly antiobesity effects in overweight/obese polycystic ovary syndrome (PCOS) patients. However, there was no literature to compare the antiobesity effects of these two medicines. Therefore, a systematic review and meta-analysis were conducted in our present study to evaluate the antiobesity effects of GLP-1RAs either as monotherapy or combined with MET in comparison with MET alone in overweight/obese PCOS patients. Methods All randomized controlled trials (RCTs) which reported the efficacy of GLP-1RAs and MET in overweight/obese PCOS patients in Medline (from Pubmed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were independently searched by two reviewers. The random-effect model was used to pool data extracted from the included literature. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD42020173199). Results A total of eight eligible RCTs were finally enrolled in our meta-analysis from the 587 retrieved literature. The results showed that GLP-1RAs alone or combined with MET was associated with a greater weight loss (N = 318, WMD = −2.61, 95% CI: −3.51 to −1.72, P ≤ 0.001, I2 = 77.5%), more obvious reduction of waist circumference (N = 276, WMD = −3.46, 95% CI: −4.36 to −2.56, P ≤ 0.001, I2 = 0.0%), and body mass index (BMI) (N = 318, WMD = −0.93, 95% CI: −1.60 to −0.26, P=0.007, I2 = 84.9%) in overweight/obese PCOS patients when compared with MET alone. Further sensitivity analysis demonstrated that the meta-analysis results of the efficacy differences in terms of body weight, waist circumference, and BMI were relatively stable and reliable. Conclusion Our meta-analysis demonstrated that the antiobesity effect of GLP-1RAs alone or combined with MET was superior to MET alone in terms of weight loss, the reduction of waist circumference, and BMI. More large-scale, high-quality RCTs are needed to further confirm these results in PCOS patients.
A Contact-Mode Triboelectric Nanogenerator for Energy Harvesting from Marine Pipe Vibrations

Structural health monitoring is of great significance to ensure the safety of marine pipes, while powering the required monitoring sensors remains a problem because the ocean environment is not amenable to the traditional ways of providing an external power supply. However, mechanical energy due to the vortex-induced vibration of pipelines may be harvested to power those sensors, which is a convenient, economic and environmentally friendly way. We here exploit a contact-separation mode triboelectric nanogenerator (TENG) to create an efficient energy harvester to transform the mechanical energy of vibrating pipes into electrical energy. The TENG device is composed of a tribo-pair of dielectric material films that is connected to a mass-spring base to guarantee the contact-separation motions of the tribo-pair. Experimental tests are conducted to demonstrate the output performance and long-term durability of the TENG device by attaching it to a sample pipe. A theoretical model for the energy harvesting system is developed for predicting the electrical output performance of the device. It is established that the normalized output power depends only on two compound variables with all typical factors taken into consideration simultaneously. The simple scale law is useful to reveal the underlying mechanism of the device and can guideline the optimization of the device based on multi-parameters analyses. The results here may provide references for designing contact-mode TENG energy harvesting devices based on the vibration of marine pipes and similar structures.
Regulation of Glucose Metabolism by MuRF1 and Treatment of Myopathy in Diabetic Mice with Small Molecules Targeting MuRF1

The muscle-specific ubiquitin ligase MuRF1 regulates muscle catabolism during chronic wasting states, although its roles in general metabolism are less-studied. Here, we metabolically profiled MuRF1-deficient knockout mice. We also included knockout mice for MuRF2 as its closely related gene homolog. MuRF1 and MuRF2-KO (knockout) mice have elevated serum glucose, elevated triglycerides, and reduced glucose tolerance. In addition, MuRF2-KO mice have a reduced tolerance to a fat-rich diet. Western blot and enzymatic studies on MuRF1-KO skeletal muscle showed perturbed FoxO-Akt signaling, elevated Akt-Ser-473 activation, and downregulated oxidative mitochondrial metabolism, indicating potential mechanisms for MuRF1,2-dependent glucose and fat metabolism regulation. Consistent with this, the adenoviral re-expression of MuRF1 in KO mice normalized Akt-Ser-473, serum glucose, and triglycerides. Finally, we tested the MuRF1/2 inhibitors MyoMed-205 and MyoMed-946 in a mouse model for type 2 diabetes mellitus (T2DM). After 28 days of treatment, T2DM mice developed progressive muscle weakness detected by wire hang tests, but this was attenuated by the MyoMed-205 treatment. While MyoMed-205 and MyoMed-946 had no significant effects on serum glucose, they did normalize the lymphocyte–granulocyte counts in diabetic sera as indicators of the immune response. Thus, small molecules directed to MuRF1 may be useful in attenuating skeletal muscle strength loss in T2DM conditions.
Study on the Stability of the Electrical Connection of High-Temperature Pressure Sensor Based on the Piezoresistive Effect of P-Type SiC

In this study, a preparation method for the high-temperature pressure sensor based on the piezoresistive effect of p-type SiC is presented. The varistor with a positive trapezoidal shape was designed and etched innovatively to improve the contact stability between the metal and SiC varistor. Additionally, the excellent ohmic contact was formed by annealing at 950 °C between Ni/Al/Ni/Au and p-type SiC with a doping concentration of 1018cm−3. The aging sensor was tested for varistors in the air of 25 °C–600 °C. The resistance value of the varistors initially decreased and then increased with the increase of temperature and reached the minimum at ~450 °C. It could be calculated that the varistors at ~100 °C exhibited the maximum temperature coefficient of resistance (TCR) of ~−0.35%/°C. The above results indicated that the sensor had a stable electrical connection in the air environment of ≤600 °C. Finally, the encapsulated sensor was subjected to pressure/depressure tests at room temperature. The test results revealed that the sensor output sensitivity was approximately 1.09 mV/V/bar, which is better than other SiC pressure sensors. This study has a great significance for the test of mechanical parameters under the extreme environment of 600 °C.
Integrative Analysis Identified Key Schizophrenia Risk Factors from an Abnormal Behavior Mouse Gene Set

Schizophrenia (SCZ) is a severe chronic psychiatric illness with heterogeneous symptoms. However, the pathogenesis of SCZ is unclear, and the number of well-defined SCZ risk factors is limited. We hypothesized that an abnormal behavior (AB) gene set verified by mouse model experiments can be used to better understand SCZ risks. In this work, we carried out an integrative bioinformatics analysis to study two types of risk genes that are either differentially expressed (DEGs) in the case-control study data or carry reported SCZ genetic variants (MUTs). Next, we used RNA-Seq expression data from the hippocampus (HIPPO) and dorsolateral prefrontal cortex (DLPFC) to define the key genes affected by different types (DEGs and MUTs) in different brain regions (DLPFC and HIPPO): DLPFC-kDEG, DLPFC-kMUT, HIPPO-kDEG, and HIPPO-kMUT. The four hub genes (SHANK1, SHANK2, DLG4, and NLGN3) of the biological functionally enriched terms were strongly linked to SCZ via gene co-expression network analysis. Then, we observed that specific spatial expressions of DLPFC-kMUT and HIPPO-kMUT were convergent in the early stages and divergent in the later stages of development. In addition, all four types of key genes showed significantly larger average protein–protein interaction degrees than the background. Comparing the different cell types, the expression of four types of key genes showed specificity in different dimensions. Together, our results offer new insights into potential risk factors and help us understand the complexity and regional heterogeneity of SCZ.
The Self-Assembly and Design of Polyfunctional Nanosystems

The current task of the molecular sciences is to create unique nanostructured materials with a given structure and with specific physicochemical properties on the basis of the existing wide range of molecules of natural and synthetic origin. A promising and inexpensive way to obtain nanostructured materials is the spontaneous self-assembly of molecular building blocks during random collisions in real dispersive systems in solution and at interfaces. This editorial aims to summarize the major points from the 11 scientific papers that contributed to the special issue “The Self-Assembly and Design of Polyfunctional Nanosystems”, assessing the modern self-assembly potential and strategies for maintaining sustainable development of the nanoindustry.
The Potentially Therapeutic Role of EPAC in Curbing the Process of Idiopathic Pulmonary Fibrosis via Differential Cellular Pathways

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosis disease caused by genetic susceptibility (causative) and other indirect risk factors such as smoking, micro-aspiration and air pollution. Repeated damage of lung epithelial cells can cause fibroblast activation and excessive collagen will lead the scar formation and severe fibrosis. It has been decades since drugs for the treatment of IPF were developed, but clinical choices were limited. Exchange Protein directly Activated by cAMP (EPAC), as a newly emerging cAMP (adenosine 3ʹ,5ʹ-cyclic monophosphate) downstream molecule, plays a vital role in the cellular pathways of IPF such as inhibiting fibroblast proliferation, stress fiber formation and epithelium cell adhesion, so it may be a novel target for drug development and treatment for curbing IPF. Here, we hypothesize that EPAC may participate in the signaling pathways related to IPF in different cell types (fibroblasts; airway smooth muscle cells; vascular endothelial cells; lung epithelial cells; macrophages; mesenchymal stem cells; T cells), thereby playing a potentially therapeutic role in resisting the process of fibrosis. We summarize the current correlation between EPAC and IPF in these different cell types, and further insights into EPAC will help to optimize the pharmacological treatment for IPF.
Inactivation of Bacteria and Biomolecules by Low-Pressure Plasma Discharges

The inactivation of bacteria and biomolecules using plasma discharges were investigated within the European project BIODECON. The goal of the project was to identify and isolate inactivation mechanisms by combining dedicated beam experiments with especially designed plasma reactors. The plasma reactors are based on a fully computer-controlled, low-pressure inductively-coupled plasma (ICP). Four of these reactors were built and distributed among the consortium, thereby ensuring comparability of the results between the teams. Based on this combinedeffort,theroleofUVlight,ofchemicalsputtering(i.e.thecombinedimpactofneutrals and ions), and of thermal effects on bacteria such as Bacillus atrophaeus, Aspergillus niger ,a s well as on biomolecules such as LPS, Lipid A, BSA and prions have been evaluated. The particle fluxes emerging from the plasmas are quantified by using mass spectrometry, Langmuir probe measurements, retarding field measurements and optical emission spectroscopy. The effects of the plasma onthe biologicalsystems are evaluatedusingatomic force microscopy, ellipsometry, electrophoresis, specially-designed western blot tests, and animal models. A quantitative analysis of the plasma discharges and the thorough study of their effect on biological systems led to the identification of the different mechanisms operating during the decontamination process.OurresultsconfirmtheroleofUVinthe200‐250nmrangefortheinactivationofmicroorganisms and a large variability of results observed between different strains of the same species. Moreover, we also demonstrate the role of chemical sputtering corresponding to the synergism between ion bombardment of a surface with the simultaneous reaction of active species such as O, O2 or H. Finally, we show that plasma processes can be efficient against different micro-organisms, bacteria and fungi, pyrogens, model proteins and prions. The effect of matrices is described, and consequences for any future industrial implementation are discussed.
An Efficient, Counter-Selection-Based Method for Prophage Curing in Pseudomonas aeruginosa Strains

Prophages are bacteriophages in the lysogenic state, where the viral genome is inserted within the bacterial chromosome. They contribute to strain genetic variability and can influence bacterial phenotypes. Prophages are highly abundant among the strains of the opportunistic pathogen Pseudomonas aeruginosa and were shown to confer specific traits that can promote strain pathogenicity. The main difficulty of studying those regions is the lack of a simple prophage-curing method for P. aeruginosa strains. In this study, we developed a novel, targeted-curing approach for prophages in P. aeruginosa. In the first step, we tagged the prophage for curing with an ampicillin resistance cassette (ampR) and further used this strain for the sacB counter-selection marker’s temporal insertion into the prophage region. The sucrose counter-selection resulted in different variants when the prophage-cured mutant is the sole variant that lost the ampR cassette. Next, we validated the targeted-curing with local PCR amplification and Whole Genome Sequencing. The application of the strategy resulted in high efficiency both for curing the Pf4 prophage of the laboratory wild-type (WT) strain PAO1 and for PR2 prophage from the clinical, hard to genetically manipulate, 39016 strain. We believe this method can support the research and growing interest in prophage biology in P. aeruginosa as well as additional Gram-negative bacteria.
How Healthy Are Health-Related Behaviors in University Students: The HOLISTic Study

The aim of this cross-sectional study was to assess the health-related behaviors among university students, with emphasis on health sciences students from Croatia, Italy, Lebanon, Poland, Romania, Spain and Turkey. We included 6222 students in Medicine, Dentistry, Nursing, Pharmacy, Nutrition and Dietetics, Sports Sciences, Veterinary, and Economics enrolled between April 2018 and March 2020. We assessed dietary patterns, sleeping habits, physical activity and perceived stress among students by means of validated questionnaires. The median age ranged between 19 and 24 years, smoking prevalence between 12.0% and 35.4%, and body mass index (BMI) ranged between 21.1 and 23.2 kg/m2. Breakfast was less often and more often consumed daily in Turkey (36.7%), and Italy (75.7%), respectively. The highest Mediterranean diet score was recorded in Spain and Italy, and the lowest in Turkey, followed by students from Croatia, Lebanon, Poland and Romania. Sleep duration, physical activity and stress perception also differed between countries. Multivariable regression analysis revealed a small, but positive association between BMI and several characteristics, including age, female gender, smoking, physical activity, mobile phone use, and perceived stress. A negative association was found between BMI and sleep duration on non-working days. Self-rated health perception was positively associated with female gender, breakfast, physical activity, and time spent studying, and negatively with BMI, smoking and stress. Our results demonstrated diverse habits in students from different countries, some of which were less healthy than anticipated, given their educational background. Greater emphasis needs to be placed on improving the lifestyle of these adolescents and young adults, who will be tomorrow’s healthcare workers.
Advantages of Additive Manufacturing for Biomedical Applications of Polyhydroxyalkanoates

In recent years, biopolymers have been attracting the attention of researchers and specialists from different fields, including biotechnology, material science, engineering, and medicine. The reason is the possibility of combining sustainability with scientific and technological progress. This is an extremely broad research topic, and a distinction has to be made among different classes and types of biopolymers. Polyhydroxyalkanoate (PHA) is a particular family of polyesters, synthetized by microorganisms under unbalanced growth conditions, making them both bio-based and biodegradable polymers with a thermoplastic behavior. Recently, PHAs were used more intensively in biomedical applications because of their tunable mechanical properties, cytocompatibility, adhesion for cells, and controllable biodegradability. Similarly, the 3D-printing technologies show increasing potential in this particular field of application, due to their advantages in tailor-made design, rapid prototyping, and manufacturing of complex structures. In this review, first, the synthesis and the production of PHAs are described, and different production techniques of medical implants are compared. Then, an overview is given on the most recent and relevant medical applications of PHA for drug delivery, vessel stenting, and tissue engineering. A special focus is reserved for the innovations brought by the introduction of additive manufacturing in this field, as compared to the traditional techniques. All of these advances are expected to have important scientific and commercial applications in the near future.
Model accuracy for economic optimizing controllers : the bias update case

In many advanced control applications the numbers of manipulated and controlled variables are not the same. A combination of steady-state economic optimization and model predictive control has been employed to exploit the optimization opportunities presented by such non-square systems. The economic optimization subsystem uses a process model and is usually coupled with a model updating scheme to compensate for plant/model mismatch. Care must be exercised during the design of such a system to ensure the model-based optimization yields operating conditions which are optimal for the true plant. We present a rigorous criterion for determining under what conditions the model-based optimization embedded within the model predictive controller, using bias update, is capable of finding the plant optimum despite plant/model mismatch. The model accuracy criterion can be applied by solving an appropriate nonlinear programming problem. Further, it is shown that when the embedded model-based optimization problem has linear constraints, the bias update method will ensure convergence to the plant optimum, providing the model accuracy criterion is satisfied and an appropriate filter is included in the feedback path. Discussions are concluded with a demonstration of the methods on a real-time gasoline blending control and optimization problem
Quality Assurance in Modern Gynecological HDR-Brachytherapy (Interventional Radiotherapy): Clinical Considerations and Comments

Simple Summary This is a focused review discussing quality assurance during interventional brachytherapy in gynecological cancers. This topic is very large and is usually addressed from the technical and physical sides, therefore, we decided to select “hot-spots” under this large title and discuss them from the point of view of clinicians. We hope that this concise and focused review will help clinicians in improving their quality assurance protocols and draw attention to the discussed issues. Abstract The use of brachytherapy (interventional radiotherapy) in the treatment of gynecological cancers is a crucial element in both definitive and adjuvant settings. The recent developments in high-dose rate remote afterloaders, modern applicators, treatment-planning software, image guidance, and dose monitoring systems have led to improvement in the local control rates and in some cases improved the survival rates. The development of these highly advanced and complicated treatment modalities has been accompanied by challenges, which have made the existence of quality assurance protocols a must to ensure the integrity of the treatment process. Quality assurance aims at standardizing the technical and clinical procedures involved in the treatment of patients, which could eventually decrease the source of uncertainties whether technical (source/equipment related) or clinical. This commentary review sheds light (from a clinical point of view) on some potential sources of uncertainties associated with the use of modern brachytherapy in the treatment of gynecological cancers.