This study was to designed to develop sorafenib-loaded polymeric nanoparticles, surface-modified with pluronic F-127 for the effective treatment of hepatocellular (HCC) and renal cell carcinomas (RCC). Poly lactic coglycolic acid (PLGA) was used to encapsulate different concentrations of sorafenib by a simple modified solvent evaporation method applying pluronic F-127 as a surfactant and coating agent. The preformulation and characterization studies were conducted to evaluate the incompatibilities among sorafenib, PLGA and pluronic F-127, and physicochemical properties of the formulations, respectively. The sizes of the coated and plain PLGA nanoparticles were ~140 ± 14.7 nm and ~ 120 ± 10.1 nm, respectively. It has been confirmed from the in vitro release studies that PLGA sustained the release of sorafenib, avoiding the initial burst release, while the in vivo studies demonstared that surface-modified nanoparticles have greater affinity in the target aorgans than plain PLGA nanoparticles and free drug keeping the dose constant (20 mg/kg body weight). The delivery of sorafenib-loaded polymeric PLGA nanoparticles into the target tissues and their pharmacokinetic parameters have been improved significantly compared to the reported formulations.

Grape pomace is a byproduct of wineries and sustainable source of bioactive phenolic compounds. Encapsulation of phenolics with a well-chosen coating may be a promising means of delivering them to the intestine, where they can then be absorbed and exert their health-promoting properties. Ionic gelation of grape pomace extract with natural coatings (sodium alginate and its combination with maltodextrins, gelatin, chitosan, tragacanth gum, and gum arabic) was performed, and the resulting hydrogel microbeads were then air-, vacuum-, or freeze-dried to prevent their spoilage. The physicochemical characterization (size, shape, texture, and morphology) of the microbeads and the in vitro release of phenols from microbeads were studied and a good relationship between them was established. Freeze-dried microbeads showed the highest cumulative release of phenols as in the intestinal phase (23.31 – 43.27 mgGAE/gMB), followed by vacuum-dried (23.31 - 35.41 mgGAE/gMB) and air-dried (22.74 – 31.38 mgGAE/gMB), while the most suitable release dynamics in the intestinal phase were observed for alginate-based microbeads combined with gelatin (58.4 %), gum arabic (34 %) and 1.5 % w/v chitosan (15.3 %). The results highlight the importance of developing encapsulated formulations containing a natural source of bioactive compounds that can be used in various functional foods and pharmaceutical products.

Antibody-Drug Conjugates (ADCs) are a powerful therapeutic modality for cancer treatment. ADCs are multi-functional biologics in which a disease-targeting antibody is conjugated to an effector payload molecule through a linker. The success of currently used ADCs has been largely attributed to the development of linker systems which allow targeted release of cytocidal payload drugs inside cancer cells. Many lysosomal proteases are over-expressed in human cancers. They can effectively cleave a variety of peptide sequences, which can be exploited in the design of ADC linker systems. As a well-established linker, valine-citrulline-p-aminobenzyl carbamate (ValCitPABC) is used in many ADCs that are already approved or under preclinical and clinical development. Although ValCitPABC and related linkers are readily cleaved by cathepsins in the lysosome while remaining reasonably stable in human plasma, many studies have shown that they are susceptible to carboxylesterase 1C (Ces1C) in mouse and rat plasma, which hinders preclinical evaluation of the ADCs. Furthermore, neutropenia and thrombocytopenia, two of the most commonly observed dose-limiting adverse effects of ADCs, are believed to result from the premature hydrolysis of ValCitPABC by human neutrophil elastase. In addition to cathepsin-cleavable linkers, there is also growing interest in legumain-sensitive linkers for ADC development. Increasing plasma stability while maintaining lysosomal cleavability of ADC linkers is an objective of intensive current research. This review reports recent advances in the design and structure-activity relationship studies of various peptide/peptidomimetic linkers in this field.

Differences in the physical and chemical properties of reclaimed water (RW) and natural surface water (SW) lead to the differences in terms of nitrogen and phosphorus release when pipeline sediments enter these water bodies. The nitrogen and phosphorus release kinetics from pipe sediments with different particle sizes have been investigated. The results demonstrated that both SW and RW had a pH buffering effect after sediment addition, and the final pH (approximately 8.1) of RW was lower. The release of total phosphorus (TP) and ammonia nitrogen ( NH₄⁺-N) fitted the first-order kinetic model where the release of TP reached equilibrium; TP release was inhibited in both SW and RW, where RW exhibited the lowest (by a factor of 1.23~2.44) release (0.002 mg/g). The release of NH4+-N was promoted in both SW and RW; the maximum release in RW was 0.0188 mg/g. The amounts of NH₄⁺-N released in SW and RW were 1.02-1.40 and 1.30-1.80 times that of the control group (CG), respectively. The percentage of TP and NH₄⁺-N release in the three groups was highest in 75-154 μm pipe sediment, reaching 34.53% and 43.51% in SW and RW, respectively. These results can assist in the development of water quality evolution models for specific urban scenarios, and provide important guidance for the precise regulation of recharge water quality during and after rainfall.

Lipid mesophases are being intensively studied as potential candidates for drug-delivery purposes. Extensive experimental characterization has unveiled a wide palette of release features depending on the nature of the host lipids and of the guest molecule, as well as on the environmental conditions. However, only few simulation works have addressed the matter, which hampers a solid rationalization of the richness of outcomes observed in experiments. Particularly, to date there are no theoretical works addressing the impact of hydropathy on the transport of a molecule within lipid mesophases, despite the significant fraction of hydrophobic molecules among currently-available drugs. Similarly, the high heterogeneity of water mobility in the nanoscopic channels within lipid mesophases has also been neglected. To fill this gap, we introduce here a minimal model to account for these features in a lamellar geometry, and systematically study the role played by hydropathy and water-mobility heterogeneity by Brownian-dynamics simulations. We unveil a fine interplay between the presence of free-energy barriers, the affinity of the drug for the lipids, and the reduced mobility of water in determining the net molecular transport. More in general, our work is an instance of how multiscale simulations can be fruitfully employed to assist experiments in release systems based on lipid mesophases.

Surface modification of polypropylene (PP) films is achieved using gamma-irradiation-induced grafting to proffer with antimicrobial activity. The copolymer was obtained through a versatile two-step route; pristine PP is exposed to gamma rays and grafted using methyl methacrylate (MMA), then N-vinylimidazole (NVI) is grafted onto the copolymer PP-g-MMA by simultaneous irradiation. The characterization included Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), Thermogravimetric Analysis (TGA), X-ray Photoelectron Spectroscopy (XPS), and physicochemical analysis of swelling and contact angle. The copolymer (PP-g-MMA)-g-NVI was loaded with vancomycin, and the drug released was quantified by UV-vis spectrophotometry at different pH. The surface of (PP-g-MMA)-g-NVI exhibited pH-responsiveness and moderate hydrophilicity, suitable properties for controlled drug release.

In this study, a slow-release urea fertilizer hydrogel was synthesized from hydroxyl propyl methyl cellulose, polyvinyl alcohol and glycerol blends with paper (blended paper) as second layer. The fertilizer hydrogel was characterized by SEM, XRD and FTIR. Its retention in sandy soil, swelling behavior in distilled and tap water as well as slow-release behavior to urea were investigated. The results indicated that the fertilizer had good slow-release properties and ability to retain water in soil. However, the addition of blended paper as a second layer matrix was found to help improve the release properties of the fertilizer. The swelling kinetic of the hydrogel followed the Schott’s Second order model. The release kinetics of urea in water was best described by the Zero order model signifying that the release behavior was independent of fertilizer concentration

Background: Spine shape parameters, such as leg length, kyphotic or lordotic angle, are influenced by low back pain. There is also evidence that the thoracolumbar fascia plays a role in such pa-thologies. This study examined the immediate effects of a myofascial release technique (MFR) on the thoracolumbar fascia and of an osteopathic treatment (OMT) on postural parameters in pa-tients with acute low back pain (aLBP). Methods: This study was a single-blind randomized pla-cebo-controlled trial. Seventy-one subjects (43.8 ± 10.5 years) suffering from aLBP were randomly and blinded assigned to three groups to be treated with MFR, OMT or a placebo intervention. Spinal shape parameters (functional leg length discrepancy (fLLD), kyphotic angle, lordotic an-gle) were measured before and after the intervention using video raster stereography. Results: Within the MFR group, fLLD reduced by 5.2 mm, p < 0.001 and kyphotic angle by 8.2 degrees, p < 0.001. Within the OMT group, fLLD reduced by 4.5 mm, p < 0.001 and kyphotic angle by 8.4 °, p = 0.007. Conclusion: MFR and OMT have an influence on fLLD and the kyphotic angle in aLBP patients. The interventions could have a regulating effect on the impaired neuromotor control of the lumbar muscles.

The activity of prioritizing software requirements should be done as efficiently as possible. Selecting the most stable requirements for the most important customers for the development company can be a positive factor when we consider that the available resource does not always encompass the implementation of all requirements. Quantitative methods for reaching software prioritization in releases are many in the field of Search-Based Software Engineering (SBSE). However, we show that it is possible to use qualitative Verbal Decision Analysis (VDA) methods to solve this same type of problem. Moreover, we will use the ZAPROS III-i methods to prioritize requirements considering the opinion of the decision-maker, who will participate in this process. Finally, the results obtained in the VDA structured methods were quite satisfactory when compared to the methods using SBSE. A comparison of results between quantitative and qualitative methods will be made and discussed later.

Dental caries is a public health problem worldwide according to WHO data. Among treatments in pediatric dentistry, prefabricated metal crowns (PMCs) have been one of the most successful options since they were introduced in cases of considerable tooth destruction. Our objective was to detect the presence and concentration of iron (Fe), chromium (Cr), and nickel (Ni) in saliva of patients who require rehabilitation with PMCs, before and after their placement. A quasi-experimental study was performed in 32 patients who attended dental care in a pediatric dentistry clinic at a public university and who required rehabilitation with PMCs. Parametric tests (ANOVA and Pearson correlation) were performed, and a p ≤ 0.05 was considered statistically significant. Statistically significant differences were found when comparing the Ni release before, 1 week, and 1 month after placing the crowns. Similarly, we observed a positive correlation between the number of crowns and Ni release. No tests were performed for Fe and Cr because the amounts of these metals were less than 0.1 ppb, which was not detectable by inductively coupled plasma optical emission spectrometry (ICP-OES). The levels of Fe, Cr, and Ni released were below toxic health levels. Studies are required to evaluate whether this release has negative effects at cellular levels.

Polyhydroxyalkanotes (PHA) are bio-based microbial biopolyesters with stiffness, elasticity, crystallinity and degradability tunable by the monomeric composition, bio-production strategy and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together with the fact that their monomeric and oligomeric in vivo degradation products do not exert any toxic or elsewhere negative effect to living cells or tissue of humans or animals, makes them highly stimulating for various applications in the medical field. The article provides an overview of PHA application in the therapeutic, surgical and tissue engineering area, and reviews strategies to produce PHA at purity levels high enough to be used in vivo. Tested applications of differently composed PHA and advanced follow-up products as carrier materials for controlled in vivo release of anti-cancer drugs or antibiotics, as scaffolds for tissue engineering, as guidance conduits for nerve repair or as enhanced sutures, implants or meshes are discussed from both a biotechnological and a material-scientific perspective. Particular attention is devoted to the adaptation of traditional polymer processing techniques for production of medicine-related devices based on PHA, such as melt-spinning, melt extrusion, or solvent evaporation, and to emerging processing techniques like 3D-printing, computer-aided wet-spinning, laser perforation, or electrospinning.

Hypertension (HTN) is the foremost contributor to cardiovascular diseases (CVD), which remain a leading cause of death. However, adherence to the properly prescribed dosage form is critical and challenging for patients with chronic diseases such as HTN to prevent illness progression and death. The study’s objective was to develop AMB-loaded subcutaneous implants to reduce the frequency of administration, thus improving patient compliance during HTN management. AMB subcutaneous implants were prepared using continuous hot melt extrusion technology using PCL and PLGA with dimensions of 7.5 cm (length) by 2 mm (diameter). The implants were characterized for thermal characteristics, drug-excipient incompatibilities, surface morphology, fracturability, in vitro release, and stability studies. DSC showed that the drug was in the crystalline state in the fabricated implants. Scanning Electron Microscopy (SEM) revealed a smooth surface. The lead formulation presented good drug content, showed an extended drug release profile over 30 days, and followed zero-order release kinetics with a mean dissolution time of 15 days. The formulation was stable over 30 days in accelerated stability conditions (the last time point was tested, 40℃/75% RH), and the release profile was similar to the initial drug release profile. The lead formulation showed good fracturability during textural analysis. Therefore, the hot melt extruded implants could be an alternative management strategy for conventional amlodipine besylate (AMB) formulation.

Thermostatically controlled loads have great potential to make a significant contribution to improving energy efficiency in the building sector, which is responsible for 40% of greenhouse gas emissions in the EU. This, in addition to the environmental damage, represents a huge expense in the electricity bill. Therefore, it is very important to train engineers on how to design energy management systems for TCLs. With this goal in mind, it would be very useful to have a simulation-based educational tool (SBET) to understand thermostatically controlled loads, their characteristics and possibilities in energy efficiency. In addition, it would be very useful if this tool could be introduced in engineering curricula to help students to be better trained and enter the labor market with more opportunities. Based on the shortcomings detected, this work develops a SBET specifically designed to teach about TCLs (SBET-TCLs), both about their intrinsic characteristics and their better management. To verify the developed SBET-TCL, it has been tested in a real scenario: A survey was carried out among the students of the subject 'Alternative Energy Sources' of the degrees of Industrial Engineering. The results show that the use of SBET-TCL has very positive effects on the learning process.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

Post-harvest handling and ripening techniques have an impact on peach quality and shelf life, which has a big impact on consumer satisfaction and market competitiveness. This review paper examines recent advancements in ripening techniques and post-harvest technologies with the goal of improving peach fruit quality and sustainability. The factors impacting fruit quality after harvest and the physiological changes that occur throughout peach ripening are fully explained. For maintaining peach freshness and reducing losses, novel handling methods like modified atmosphere packaging (MAP) and controlled atmosphere storage (CAS) have been investigated. The study explores the possibilities of nanotechnology applications and low-temperature storage for prolonging shelf life while maintaining texture, flavor, and aroma. Examining the effectiveness and waste reduction potential of automation and mechanization in post-harvest activities. The paper also discusses ethylene-based and non-ethylene-based ripening agents, as well as innovative techniques including gene editing and RNAi technology for controlled and delayed ripening. Analyses are done on how these technologies affect the sensory qualities and nutrient profiles of peaches. The study emphasizes the significance of sustainable practices in the peach industry by focusing on waste reduction, resource efficiency, and circular economy integration. Post-harvest technologies' potential environmental consequences have been taken into consideration and the paper encourages more study and cooperation to increase sustainability.

Despite the expansion of financial institutions and proliferation of mobile financial services, reaching the unbanked and bringing them under formal financial services has become a policy concern in many developing countries. Due to the lack of financial accounts, unbanked people prefer informal, risky, and inconvenient mechanisms for receiving, sending and transferring money. Previous studies rely much on common intervention like no account maintenance and opening fees, easy documentation processes and money subsidies for opening financial accounts. This study aims to examine the impact of the motivational workshop on opening savings accounts through causality among the unbanked people in a setting where the respondents are unbanked despite having all the requirements and many institutional offers for opening savings accounts. We encouraged the unbanked people through a one-hour-long motivational workshop to open saving account. Based on our cross-sectional data and randomized controlled trial experiment among 505 unbanked Village Defense Party (VDP) members at Dhubil Union under Sirajganj in Bangladesh, we have the evidence that motivational workshop positively impacts opening ac-counts by 32.33 percent. However, the account opening rate differs in terms of respondent’s pref-erence for financial institutions. Our study also finds that unbanked people have the highest pref-erence for mobile financial services for opening accounts resulting in 15.33 percent. The result of the study has some policy implications for adopting effective strategies of financial access in many developing countries.

Indoor crop cultivation systems such as vertical farms or plant factories necessitate artificial lighting. Light spectral quality can affect plant growth and metabolism and, consequently, the amount of biomass produced and the value of the produce. Conflicting results on the effects of light spectrum in different plant species and cultivars make it critical to implement a singular lighting solution. In this study we explored the response of green and red leaf lettuce cultivars (’Aquino’, CVg, or ‘Barlach’, CVr, respectively) to long-term blue-enriched light application (WB). Plants were grown for 30 days in a growth chamber with optimal environmental condi-tions (temperature: 20°C, relative humidity: 60%, ambient CO2, Photon Flux Density (PFD) of 260 µmol m-2 s-1 over an 18-h photoperiod). At 15 days after sowing (DAS) white spectrum LEDs (WW) were compared to WB (λPeak = 423 nm) maintaining the same PFD of 260 µmol m-2 s-1. At 30 DAS, both lettuce cultivars resulted adapted to the blue light variant, though the adaptive re-sponse was specific to the variety. Rosette weight, light use efficiency and maximum operating efficiency of PSII photochemistry in the light, Fv/Fm’, were comparable between the two light treatments. Significant light quality effect was detected on stomatal density and conductance (20% and 17% increase under WB, respectively, in CVg) and, on the modified anthocyanin re-flectance index (mARI) (40% increase under WB, in CVr). Net photosynthesis response was gen-erally stronger in CVg compared to CVr; e.g. net photosynthetic rate, Pn, at 1000 µmol m-2 s-1 PPFD increased from WW to WB by 23% in CVg, compared to 18% in CVr. Results obtained suggest the occurrence of distinct physiological adaptive strategies in green and red pigmented lettuce cultivars to adapt to the higher proportion of blue light environment.

The article is aimed at a brief comparison and analysis of the results of queries to IEEE Xplore and the leading abstract databases Scopus and Web of Science to identify research trends. Some errors in the Author Keywords in Web of Science have been revealed. Therefore, a more detailed analysis was conducted by comparing different types of key terms for IEEE Xplore and Scopus platforms only. I used IEEE Access journal metadata as indexed on both platforms. The sample match for IEEE Xplore and Scopus was achieved by comparing DOI. The IEEE Xplore metadata contains more types of key terms, which provides an advantage in analyzing research trends. Using NSPEC Controlled Terms from expert-compiled vocabulary provides a more stable data, which gives an advantage when considering the change of terms over time. Apriori, an algorithm for finding association rules, has been used to compare co-occurrence of terms for a more detailed description of sample subjects on both platforms. VOSviewer was used to analyze trends in scientific research based on IEEE Xplore data. The 2011-2021 ten-year period was divided into two sub-intervals for comparing the occurrence of Author Keywords, IEEE Terms, and NSPEC Controlled Terms. Using the IEEE conference proceedings bibliometric data, I illustrated the importance of context in estimating the rate of growth of publishing activity on a topic of interest.

Physiological storage disorders continue to cause sizable economic losses in a range of commercially important pomefruit cultivars. Given similar storage regimes, the incidence and severity of browning disorders in the apple cultivar ‘Braeburn’ can vary in different years in a way that can be explained by the interaction of preharvest seasonal and orchard factors. Over a three-year period (2016 to 2019) at the Kompetenzzentrum Obstbau-Bodensee (KOB) in Southwest Germany a range of orchard and storage treatments were conducted for: air temperature during cell division for three weeks post petalfall or during four weeks preharvest, calcium orchard sprays, crop load and harvest timings. Following controlled atmosphere (CA) storage, the disorder incidence for internal browning and cavity formation varied markedly over the three different growing seasons. Crop load treatments strongly influenced the expression of browning disorders in all years. Differences in air temperatures (△ +/- 2 °C compared to ambient) during the cell division period showed little effect on browning incidence. Warm night temperatures (>10 °C) prior to harvest can reduce internal browning in ‘Braeburn’ apples during CA storage and shelf-life.

Background and objectives: Traditional intravenous, patient-controlled analgesia (PCA) uses a fixed-rate continuous background infusion mode. However, some patients suffer from inadequate analgesia or opioid-related adverse effects due to the biphasic pattern of postoperative pain. Therefore, we investigated the postoperative analgesic efficacy of PCA using an optimizing background infusion mode (OBIM), where the background injection rate varies depending on the patient's bolus demand. Materials and Methods: We prospectively enrolled 204 patients who underwent laparoscopic cholecystectomy in a randomized, controlled, double-blind study. Patients were allocated into either the optimizing (group OBIM) or the traditional background infusion group (group TBIM). The numeric rating scale (NRS) score for pain was evaluated at admission to and discharge from the recovery room, as well as at the 6th, 24th, and 48th postoperative hours. Data of bolus demand count, total infused volume, and background infusion rate was downloaded from the PCA device at 30-min intervals until the 48th postoperative hour. Results: The NRS score was not significantly different between groups throughout the postoperative period (P = 0.621), decreasing with time in both groups (P < 0.001). The bolus demand count was not significantly different between groups throughout (P = 0.756). The mean cumulative infused PCA volume was lower in group OBIM [84.0 (95% confidence interval: 78.9−89.1) mL) than in group TBIM [102 (97.8−106.0) mL] (P < 0.001). The background infusion rate was significantly different between groups throughout (P < 0.001); it was higher in group OBIM than in group TBIM before the 12th postoperative hour, and lower from the 18th to the 48th postoperative hours. Conclusions: The OBIM combined with bolus dosing is useful in that it reduces the cumulative PCA volume compared to the TBIM combined with bolus dosing, while yielding comparable postoperative analgesia and bolus demand in patients undergoing laparoscopic cholecystectomy.

The functionalization of polymeric substances is of great interest for the development of innovative materials for advanced applications. For many decades, the functionalization of chitosan has been a convenient way to improve its properties with the aim to prepare new materials with specialized characteristics. In the present article, we summarize the latest methods for the modification and derivatization of chitin and chitosan, trying to introduce specific functional groups under experimental conditions, which allow a control over the macromolecular architecture. This is motivated because an understanding of the interdependence between chemical structure and properties is an important condition for proposing innovative materials. New advances in methods and strategies of functionalization such as click chemistry approach, grafting onto copolymerization, coupling with cyclodextrins and reactions in ionic liquids are discussed.

β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, of cellular glucose uptake, of lipolysis, and of thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to lack of clinically relevant changes of body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans.

In the land use planning framework in the neighbourhood of industrial facilities, the current approach to predicting the consequences of massive toxic gas releases is generally based on Gaussian or integral models. For many years, CFD models have been more and more used in this context, in accordance with the development of High-Performance Computing (HPC). The present paper focuses on harmonizing input data for Atmospheric Transport and Dispersion (AT&amp;D) modelling between the widely used approaches. First, a synthesis of the practice’s harmonization for atmospheric dispersion modelling within the framework of risk assessment is presented. Then, these practices are applied to a large-scale INERIS ammonia experimental release. For illustration purposes, the impact of the proposed harmonization will be evaluated using different approaches: the SLAB model, the FDS model and the Code_Saturne model. The two main focuses of this paper are the adaptation of the source term dealing with a massive release and the wind flow modelling performance using an experimental signal for CFD models inflow. Finally, comparisons between the modelling and experimental results enable checking the consistency of these approaches and reinforce the importance of the input data harmonization for each AT&amp;D modelling approach.

Our knowledge of biology and mast cell (MC) function, as well as disorders associated with the pathologic activation of MCs has been evolving over the last few decades. Anaphylaxis, mast cell activation syndrome (MCAS) and mastocytosis are interrelated yet distinct conditions within the spectrum of mast cell activation disorders. Nevertheless, all three conditions can co-exist in one and same patient, as pathologic MC activation is the key finding in all three. When mediator release is excessive and involves multiple systems, anaphylaxis and MCAS may occur. Furthermore, mastocytosis is a clonal disorder of MCs and often presents with anaphylaxis and MCAS. Nevertheless, in some cases even proliferative and accumulative features of MCs in mastocytosis can account for symptoms and disease progression. In each case, diagnosis can be only made when diagnostic consensus criteria are fulfilled. The current article aims to provide a concise clinical update and pinpoint main difficulties in diagnosing these puzzling disorders of MCs in medical practice.

Heat requirements play an important role in plant flowering, and control the flowering period of woody ornamental plants to a certain extent. In this study, the perennial potted seedlings of four typical Prunus mume cultivars 'Xiaolve', 'Baixuzhusha', 'Fenghou' and 'Danfenghou' were used as materials. The way of regulating the cultivation temperature is adopted to achieve the purpose of relieving the natural dormancy and forcing the blooming of P. mume. Its content includes the research on the heat requirements of P. mume cultivars widely planted in Beijing, and the analysis of the influence of different facility cultivation temperatures on the flowering characteristics of P. mume, providing a theoretical basis for further exploring the cultivation techniques of P. mume bonsai flowering regulation. The results showed that, according to the Growing degree-hour model, the HR of 'Xiaolve', 'Baixuzhusha', 'Fenghou' and 'Danfenghou' flower buds were 3583.70 GDH℃, 3217.30 GDH ℃, 3996.50 GDH ℃, 4732.20 GDH ℃, respectively. According to the effective accumulated temperature model, the HRs of above cultivars were 350.65 ℃, 319.30 ℃, 510.30 ℃, 558.50 ℃, respectively. In addition, the temperature of different cultivation facilities did not significantly change the flowering quality such as flower diameter and fragrance. Temperature also affects the growth and development speed, affecting the flowering time. Under the facility environment with higher temperatures, the flowering process is faster and the flowering period is shorter.

Zero-rate output (ZRO) drift induces deteriorated micro-electromechanical system (MEMS) gy-roscope performances, severely limiting its practical applications. Hence, it is vital to explore an effective method toward ZRO drift reduction. In this work, we conduct an elaborate investigation on the impacts of the internal and packaging stresses on the ZRO drift at the thermal start-up stage, and propose a temperature-induced stress release method to reduce the duration and magnitude of ZRO drift. Self-developed high-Q dual mass tuning fork gyroscopes (TFGs) are adopted to study the correlations between temperature, frequency and ZRO drift. Furthermore, a rigorous finite element simulation model is built based on the actual device and packaging structure, revealing the temperature and stresses distribution inside TFGs. Meanwhile, the relationship between temperature and stresses are deeply explored. Moreover, we introduce a temperature-induced stress release process to generate thermal stresses and reduce the temperature-related device sensitivity. By this way, the ZRO drift duration is drastically reduced from ~2000 s to ~890 s, and the drift magnitude decreases from ~0.4 °/s to ~0.23 °/s. This stress release method achieves a small bias instability (BI) of 7.903 °/h and a low angle random walk (ARW) of 0.792 °/√h, and the long-term bias performance is significantly improved.

Breast cancer is the most widespread malignancy in women from corner to corner of the world. Nanostructured lipid carrier (NLC) proved its efficacy in the treatment of cancer. NLC loaded with Imatinib (IMA) (NANIMA) was prepared and evaluated for in vitro efficacy in MCF-7 breast cancer cells. Hot homogenization method was used for the preparation of NANIMAs. Aqueous solution of surfactants (hot) was mixed with molten mixture of stearic acid and sesame oil (hot) under homogenization. The prepared NANIMAs were characterized and evaluated for size, polydispersity index, zeta potential, encapsulation efficiency, release studies, stability studies and MTT assay (cytotoxicity studies). The optimized NANIMA revealed particle size of 104.63 ± 9.55 d.nm, PdI of 0.227 ± 0.06 and EE of 99.79 ± 0.03. All NANIMAs revealed slow and sustained release behaviour. The surfactants used in the preparation of NANIMAs exhibited their effects on particle size, zeta potential, encapsulation efficiency, stability studies and release studies. The cytotoxicity studies unveiled 8.75 times increase in cytotoxicity for optimized NANIMA (IC50 = 6 µM) when compared with IMA alone (IC50 = 52.5 µM) on MCF-7 breast cancer cells. After this, NLC containing IMA possibly will be employed for the cure of breast cancer. A lesser amount of IMA loaded NLC will be sufficient than IMA alone for the treatment of breast cancer. Moreover, the patient will exhibit not as much of adverse effects as in case of IMA alone. Consequently, NANIMA could prove to be useful for effective therapeutic outcome in breast cancer treatment.

The motivation of this work is to investigate experimentally the influence of non-thermal plasma (NTP) application on the reaction kinetics of atmospheric pressure steam gasification of charcoal using a thermostatically controlled drop tube reactor. A gliding-arc generator provides about 1 kW electrical power NTP. For comparison thermal gasification is investigated under comparable flow and specific energy input conditions providing additional heat to the steam. Optical temperature measurement 20 cm flow down of the NTP zone is utilized to characterize the specific enthalpy of the reactive flow. The composition of produced syngas is measured by a gas analyzer and used for the calculation of gas flow rates. The results show a NTP-enhancement on the production of individual syngas components (H2, CO, CH4), especially on hydrogen production by around 39%. The syngas-based carbon conversion and hydrogen release are calculated from the carbon and hydrogen balance between the correspondent content in syngas and in the feedstock. The NTP promoted the carbon conversion and hydrogen release by 25% and 31%, respectively. The first-order reaction kinetics are determined by data-fitting in an Arrhenius diagram. The plasma enhanced the reaction rate coefficients by 27%. Based on experimental results and other literature, possible plasma-induced reactions are proposed.

Mere similar grades of same excipients manufactured by two different manufacturers often differ significantly that they even have an impact on the variations in final product or dosage form. Solid lipids are one of the most available options as matrix former in sustained drug delivery. Due to their chemical and physical complexity, lipids may exhibit a complex behaviour (i.e. melting crystallization and polymorphism). The aim of this study was to evaluate the physical and chemical properties of two Glyceryl Monostearate (GMS) lipids (Geleol from Gattefosse and Capmul GMS 50K from Abitec Corp. USA) and how these properties may affect during melt granulation process for sustained release applications. Thermal processing was applied on GMS samples to understand the polymorphic nature and suitability as meltable binders. Niacin was used as model drug. A thorough evaluation of GMS samples and sustained release tablets was undertaken using analytical techniques such as differential scanning calorimetry (DSC), X-ray diffraction (XRD). Moreover, melt viscosity study assisted to apprehend the behaviour of GMS samples in hot melt extrusion processing. Surface morphology of the drug and extruded granules examined via SEM and AFM revealed high level of surface interaction and dense structure of drug inside lipid matrix. The DSC and XRD study confirmed that Geleol could not withstand the heat treatment applied during thecontinuous melt granulation processing. The shifting of stable β form to an unstable α form in Geleol was detected. In the contrary case, Capmul GMS 50K was able to withstand the heat treatment supported by the applied analytical techniques. Nonetheless,both GMS samples perform differently in final dosage form. This change in stable β form to an unstable α form affected dissolution profiles at 3 months storage in accelerated condition. This study helped to interpret the complex solid-state behaviour of solid lipid extrudates with different compositions, in order to the simply and outline a suitable formulation strategy for the development of lipid-based oral dosage forms.

(1) Background: The aim of this study is to investigate the diagnostic-therapeutic problem of pelvic recurrence of rectum cancer, highlighting current surgical standards and the possible role of the minimally invasive approach. This retrospective analysis of our surgical case study wishes to enter this debate while suggesting a possible line of action, based on the site of recurrence; (2) Methods: We examined, retrospectively, all the patients diagnosed, between 2008 and 2018, with cancer of the rectum at the "Pietro Valdoni" Department of Surgery and monitored their follow-up for 5 years. The sample consisted of 368 patients with rectal neoplasm, 136 females and 232 males, with an average age of 65.8 (ranging from 37 to 86); (3) Results: In 103 of the cases, the neoplasm was located in the upper rectum (28%), in 119 cases in the middle rectum (32.3%), in 102 cases in the lower rectum (27.7%), in 31 cases (8.4%) at the level of the right/sigma junction and in 13 cases it was not possible to define the site with certainty (3.5%); (4) Conclusions: The discussion re-mains open as to which approach is best at surgical level, whether laparoscopic, robotic or open-air. Our experience informs us that the most dangerous site remains on the anastomotic site.

Controlled drainage (CD) is an important agricultural measure for maintaining soil moisture and nutrients, controlling groundwater level, and increasing crop yield. In arid regions, CD can be used to improve the water supply in agriculture and reduce environmental pollution. In this study, we investigated the effect of CD, including a drainage depth of 40 cm (CWT1) and 70 cm (CWT2) during the plant growth period, free drainage (FD), and open ditch drainage (OD) on the migration of water, nutrients, and salts in the soil; the dynamics of groundwater level; the loss of soil nitrogen; and the growth of oilseed sunflower plants. Compared with FD, CD increased the water and nutrient content in the soil, reduced nitrogen loss, and enhanced the ability of the soil to continuously supply nitrogen to the oilseed sunflower plants, which benefited plant growth at later growth stages and reduced environmental pollution. During the period between irrigation at the budding stage and harvest stage, the average soil water content in the 0–20 cm soil layer in CWT1 increased by 3.67%, 4.78%, and 0.55%, respectively, compared with that in CWT2, FD, and OD. The soil mineral content in CWT1 was 25.17%, 35.05%, and 17.78% higher than that in CWT2, FD, and OD, respectively, indicating that higher soil salinity occurred at the later stage of plant growth in CWT1, which actually had little effect on the plants due to their enhanced salt tolerance and increased need for water and nutrients at that stage. In addition, CD delayed the decline in groundwater level, which allowed the plants to use groundwater at later growth stages, and as a result the yield and water use efficiency were improved. CWT1 significantly increased oilseed sunflower yield by 4.52–11.14% and increased water use efficiency by 1.16–10.8%. Moreover, CWT1 also increased the survival rate of the oilseed sunflower plants by 2.62–2.92%, and the plants demonstrated good growth. Therefore, under CD conditions, plants used soil water and nitrogen more efficiently and, as a result, their productivity was increased, and the water quality was improved.

Background: New regional techniques can improve pain management after nephrectomy. Methods: This study was a randomized controlled trial conducted at two teaching hospitals. Patients undergoing elective open and laparoscopic nephrectomy were eligible to participate in the trial. A total of 100 patients were divided into a quadratus lumborum block (QLB) group and a control (CON) group. At the end of surgery, but while still under general anesthesia, unilateral QLB with ropivacaine was performed on the side of nephrectomy for patients in the QLB group. The main measured outcome of this study was oxycodone consumption via a patient-controlled anesthesia (PCA) pump during the first 24 hours following surgery; other measured outcomes included postoperative pain intensity assessment, patient satisfaction with pain management, and persistent pain evaluation. Results: Patients undergoing QLB needed less oxycodone than those in the CON group (34.5 mg [interquartile range 23–40 mg] vs. 47.5 mg [35–50 mg]; p<0.001). No difference between the groups was seen in postoperative pain intensity measured on the visual analog scale, except for the evaluation at hour 2, which was in favor of the QLB group (p=0.03). Patients who received QLB were more satisfied with postoperative pain management than the CON group. Persistent postoperative pain was assessed with the Neuropathic Pain Symptom Inventory (NPSI) at months 1, 3, and 6 and was found to be significantly lower in the QLB group at each evaluation (p<0.001). We also analyzed the impact of the surgery type on persistent pain severity, which was significantly lower after laparoscopic procedures than open procedures at months 1, 3, and 6. Conclusions: QLB reduces oxycodone consumption in patients undergoing open and laparoscopic nephrectomy and decreases persistent pain severity months after hospital discharge.

A humidity-sensitive demand-controlled ventilation system is known for many years. It has been developed and commonly applied in regions with an oceanic climate. Some attempts were made to introduce this solution in Poland in a much severe continental climate. The article evaluates this system's performance and energy consumption applied in an 8-floor multi-unit residential building, virtual reference building described by the National Energy Conservation Agency NAPE, Poland. The simulations using the computer program CONTAM were performed for the whole hating season for Warsaw's climate. Besides passive stack ventilation that worked as a reference, two versions of humidity-sensitive demand-controlled ventilation were checked. The difference between them lies in applying the additional roof fans that convert the system to hybrid. The study confirmed that the application of demand-controlled ventilation in multi-unit residential buildings in a continental climate with warm summer (Dfb) leads to significant energy savings. However, the efforts to ensure acceptable indoor air quality require hybrid ventilation, which reduces the energy benefits. It is especially visible when primary energy use is analyzed.

The use of natural raw substances for food preservation could provide a great contribution to food waste reducing, circular economy enhancing, and green processes application widening. Recent studies indicated that natural preservatives release kinetics significantly influenced the food preservation process. The use of porous materials as absorber for natural essential oils provided nanohybrids with excellent antioxidant and antimicrobial properties. In this study the well-known SBA-15 porous material was used to control the release of the natural preservative thyme oil on food surface and to extend the food shelf-life. Results indicated that the thyme oil loading was higher than other porous materials reported recently and the addition of SBA-15 to the LDPE increases the water/oxygen barrier. The film with the higher thyme-oil@SBA-15 nanohybrid content exhibited the slower release kinetic. The antioxidant activity of the final films ignited after 48 hours, was in the range of 60-70%, and was almost constant for 7 days. Finally, all tests indicated a sufficient improvement by the addition of thyme-oil@SBA-15 nanohybrids in the pure LDPE matrix and the concentration of wt. 10% of such nanocarriers provided the optimum final LDPE/10TEO@SBE-15 active packaging film. This material could be a potential future product for active packaging applications.

Objective The aim of this study was to examine the impact of a modern lifestyle on college female students' health, specifically focusing on their hip and knee joint mobility. The objective of this study was to assess the influence of hydraulic resistance training with the self-myofascial release technique on improving joint mobility in female college students. The training also aimed to compare the effectiveness of hydraulic resistance exercise with and without the self-myofascial release technique on hip and knee joint mobility.Methods The study used a randomized controlled trial design to recruit 30 female college students aged 18-25 through campus advertisements and announcements. Medical conditions or injuries that might have affected participation was screened. Participants were indiscriminately allocated to Group A (Hydraulic Resistance Training with Self-Myofascial Technique) or Group B (Hydraulic Resistance Training without Self-Myofascial Technique). The baseline assessments included joint range of motion (ROM) measurements using a goniometer. Certified trainers supervised the training sessions, and the data were analyzed using SD and mean using SPSS. ResultsThis study aimed to evaluate the impact of hydraulic resistance training with self-myofascial release on hip and knee joint mobility in female college students. The results showed that both groups showed improved hip and knee flexion with and without the self-myofascial release technique. However, the Group A using the self-myofascial release technique (Group A) showed a more significant enhancement, as indicated by the smaller p value compared to Group B. It has been suggested that the self-myofascial release technique may improve hip and knee joint mobility. ConclusionThis study concluded that Hydraulic Resistance Training with Self-Myofascial Release (HSMR) could improve hip and knee joint mobility among female college students. These findings suggest that integrating the self-myofascial release technique into training regimens can improve joint mobility. However, further research with larger sample sizes and extended intervention periods was needed to understand the long-term effects and sustainability of these improvements.

CO2 is widely used in the prevention and control of coal spontaneous combustion. In this manuscript, three low-rank coals with different metamorphic degrees were selected as the research objects. The temperature-programmed experiments, in-situ infrared cooling experiments, simulation of competitive adsorption of CO2 and O2 in coal pores, and simulation study of CO2 inhibition of coal oxygen composite reaction were used to obtain the role and effect of CO2 in preventing oxygen adsorption in coal at low-temperature oxidation stage. It is concluded that CO2 can displace the O2 near the pore wall to physically prevent the adsorption of O2. Through the change law of heating rate and kinetic analysis, it is found that CO2 can increase its activation energy by 5.3%-108.3% during the slow heating stage of coal, and reduce its heating rate. At around 120°C, coal loses the protective effect of CO2. From the changes of functional groups, it can be seen that when coal is cooled in CO2 atmosphere, mainly pyrolysis and condensation reactions occur due to the lack of O2. In addition, CO2 can also inhibit the chain reaction of coal's chemical adsorption of oxygen. This work provides a theoretical basis for CO2 prevention and control of coal spontaneous combustion.

With the current increase in the demand from animal and agricultural products, management of agrowaste has become critical to avoid greenhouse gas emissions. The present article investigates the applicability of ammonium bicarbonate synthesis via flash distillation to valorize and stabilize several types of anaerobic digestate produced from individual fermentations of amino acids. Prior to the development of the model in Aspen Plus v12, the description of the system aqua-ammonia-carbon dioxide provided by the electrolyte non-random two-liquid property method was validated with empirical data available in the literature. The content of CO₂ in the digestate was found to be responsible of the OH alkalinity (0.4 equivalents of acid/kg digestate), while the partial and total alkalinities (0.8 eq/kg digestate) were essentially derived from the content of NH₃. The most suitable conditions for the flash distillation were 95 ⁰C and 1 bar with the condensation occurring at 25 ⁰C. However, in order to attain the precipitation of NH₄HCO₃ in the distillate, it was necessary to consider digestates with a moisture content of 50 wt.%, since the minimum levels of inorganic nitrogen and inorganic carbon were not attained otherwise. Even under these conditions, few amino acids (i.e. arginine, glycine, and histidine) were able to provide an anaerobic digestate, upon fermentation, that would be suitable for NH₄HCO₃ stabilization. Despite alanine digestate and glutamine digestate presented sufficient concentrations of inorganic nitrogen and inorganic carbon, the NH₄HCO₃-stabilization was not feasible due to the limited volatilization of NH₃. The process of stabilization with a capacity of a tonne of digestate per hour was improved by adding hydrochloric acid or sodium hydroxide at rates 44 kg/h, leading to production of 34 kg NH₄HCO₃/h. The economic viability of this process needs to be investigated considering not only the market value of the isolated inorganic fertilizer but the carbon credits saved, resulting from handling a more stabilized organic manure. Furthermore, given the role of the volatile elements of the biogas as endogenous stripping agents, it is recommended to use a fresh and saturated digestate as feed for the flash distillation.

Dispersed silver nanoparticles (AgNPs) on the surface of titanium alloy (Ti6Al4V) and titanium alloy modified by titania nanotube layer (Ti6Al4V/TNT) substrates were produced by chemical vapor deposition method (CVD) using novel precursor of the formula [Ag₅(O₂CC₂F₅)₅(H₂O)₃]. The structure and volatile properties of this compound were determined using single crystal X-ray diffractometry, variable temperature IR spectrophotometry (VT IR), and electron inducted mass spectrometry (EI MS). The morphology and the structure of the produced Ti6Al4V/AgNPs, and Ti6Al4V/TNT/AgNPs composites were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Moreover, measurements of hardness, Young’s modulus, adhesion, and surface free energy have been carried out. The ability to release silver ions from the surface of produced nanocomposite materials immersed in PBS solution has been estimated using inductively coupled plasma mass spectrometry (ICP MS). The wettability and the surface free energy of samples were estimated on the base of contact angle studies with the use of water and diiodomethane. Among the studied surface-modified titanium alloy implants, the best nano-mechanical properties were noticed for the Ti6Al4V/TNT15/AgNPs composite. The location of silver nanoparticles inside of titania nanotubes caused their lowest release rate, which may indicate on suitable properties above mentioned type of the composite for the construction of implants with a long term of antimicrobial activity.

In order to create a smart mine, it is necessary to digitize the existing emulsion pumping station. Existing research does not achieve this task, this paper designs and manufactures a high-pressure, high-flow, high-water-based mining digital controlled unloading valve (abbreviated as HLHMDCUV), which achieves good results in both theoretical analysis and experimental testing. In order to obtain the accurate dynamic characteristics, this valve was analyzed by simulation using AMESim. Based on the dynamic performance analysis and the flow field analysis inside the valve body, the structure has been optimized to improve the performance of HLHMDCUV. The results show that the HLHMDCUV has a better dynamic characteristics, which were also demonstrated in the experiment. At the same time, the HLHMDCUV is easy to disassemble and maintain. This paper provides a theoretical basis for the design of such valves, which is conducive to the subsequent promotion of intelligent mine transformation.

To verify the authors’ mathematical model for water jet cooling of steel sheet, the previously performed experimental studies of temperature of the test plate in the roller quenching machine (RQM) were used. The calculated data of steel temperature evolution along the RQM length were compared with the readings of thermocouples inserted in the center of the test plate and at its surfaces. The core of the model is the dependence of the temperatures of film, transition and nucleate boiling regimes on the thickness of the oxide scale layer on the cooled surface. It was found that the model correctly takes into account the oxide scale on the sheet surface, flow rates and combinations of the RQM banks used, water temperature and other factors. For all experiments the calculated metal temperature corresponds well to the measured one. In the experiments with interrupted cooling, the calculated temperature plots repeat the characteristic changes in the experimental curves. The main uncertainty in the modeling of cooling in a wide temperature range can be contributed by the random nature of changes in the oxide scale thickness during water cooling. In this regard, the estimated thickness of the oxide scale layer should be considered as the main parameter for adapting the sheet temperature control process. The obtained data confirm the possibility of effective application of the model in the ACS of industrial TMCP (Thermo-Mechanical Controlled Process) systems.

Late pear cultivars, such as ‘Conference’, can be stored for a long period, with their storability depending on storage conditions. A three-year study (2011-2013) compared the impact of half-year storage using four technologies – normal atmosphere, normal atmosphere + 1-methylcyclopropene (1-MCP), controlled atmosphere, controlled atmosphere + 1-MCP – on the quality parameters of ‘Conference’ pears, such as mass loss, firmness, total soluble solids, acidity, antioxidant capacity, and the incidence of diseases and disorders. Additionally, the study analysed different storage conditions in terms of profitability, based on the market prices for pears in the seasons during which the pears were stored. The storage conditions had a very strong influence on the fruit quality parameters, and was found to affect most visibly the mass loss and the incidence of postharvest diseases and disorders. The storage of ‘Conference’ pears for 180 days in normal atmosphere is not economically viable, even if the fruit is subjected to 1-MCP treatment.

Prescribed burning and other active forest management treatments have been proven to be essential for maintaining suitable habitat conditions for many wildlife species, including the federally endangered red-cockaded woodpecker (RCW). This study examines the perception of forest management treatments of recreation users participating in various activities (hunting, hiking/backpacking, camping, off-highway vehicle riding, and canoeing/kayaking) in terms of scenic beauty and recreation satisfaction. We used photographic images to capture various forest management treatments of different intensity levels and times after treatments, and assessed users’ perception of scenic beauty and recreation satisfaction. Results indicated variation among users participating in different recreation activities, but that good quality RCW habitat offered both higher scenic beauty and higher recreation satisfaction than poor quality habitat for most user groups. Finally, recreation satisfaction was statistically equal to perceived scenic beauty from both good and poor-quality RCW habitats for most of the user groups, thus suggesting the importance of scenic beauty on forest sites in determining recreation users’ attainment of visit satisfaction. Findings conclude that forest sites developed as good quality RCW habitat in the present state also offer quality experience to recreation users, thus supporting multi-objective forestry practices in public forests.

First, a recently developed eigenfunction expansion technique, based in part on separation of the thickness-variable and partly utilizing a modified Frobenius type series expansion technique in conjunction with the Eshelby-Stroh formalism, is employed to derive three-dimensional singular stress fields in the vicinity of the front of an interfacial crack weakening an infinite bicrystalline superlattice plate, made of orthorhombic (cubic, hexagonal and tetragonal serving as special cases) phases, of finite thickness and subjected to the far-field extension/bending, in-plane shear/twisting and anti-plane shear loadings, distributed through the thickness. Crack-face boundary and interface contact conditions as well as those that are prescribed on the top and bottom surfaces of the bicrystalline superlattice plate are exactly satisfied. It also extends a recently developed concept of lattice crack deflection (LCD) barrier to a superlattice, christened superlattice crack deflection (SCD) energy barrier for studying interfacial crack path instability, which can explain crack deflection from a difficult interface to an easier neighboring cleavage system. Additionally, the relationships of the nature (easy/easy, easy/difficult or difficult/difficult) interfacial cleavage systems based on the present solutions with the structural chemistry aspects of the component phases (such as orthorhombic, tetragonal, hexagonal as well as FCC (face centered cubic) transition metals and perovskites) of the superlattice are also investigated. Finally, results pertaining to the through-thickness variations of mode I/II/III stress intensity factors and energy release rates for symmetric hyperbolic sine distributed load and their skew-symmetric counterparts that also satisfy the boundary conditions on the top and bottom surfaces of the bicrystalline superlattice plate under investigation, also form an important part of the present investigation.

Background: Antibiotic-containing carrier systems are one option that offers the advantage of releasing active ingredients over a longer period of time. In vitro sustained drug release from a carrier system consisting of microporous β-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a β-TCP ceramic and higher biodegradability than pure alginate. Methods: Dual release of daptomycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21, and 28 by HPLC and ELISA. After release, the microbial efficacy of the daptomycin was verified and the biocompatibility of the composite was tested in cell culture. Results: Daptomycin and the model compound FITC protein A (n=30) were released from the composite over 28 days. A Daptomycin release above the minimum inhibitory concentration (MIC) by day 9 and a burst release of 71.7 ± 5.9 % were observed in the loaded ceramics. Low concentrations of BMP-2 were released from the loaded ceramics over 28 days.

: This article reports on polymer (PLLA, poly(L-lactic acid)) nanosheets incorporated with Fe-ion nanoparticles, aiming at using the latter nanoparticles as source to release Fe ions to facilitate burn wound healing when such nanosheets are applied on skin as biomedical tissue. Laser ablation in liquid phase was used to produce Fe-containing nanoparticles that after incorporation into PLLA nanosheets would release Fe ions when in immersed in water. Such nanoparticles prepared in chloroform are shown by XPS to be based on iron chloride and oxide phases. After incorporation into PLLA nanosheets, the ion –release test demonstrated that Fe ions could be released successfully into water at pH 7.4, which implies that such polymer nanosheets show promise for biomedical applications as potential patches for healing burn wounds. Incorporation with two different metal ions (Fe and Zn) is shown to be efficient and both types of ions were demonstrated to be released simultaneously and with comparable release rates.

Nutrient release from marine sediments in Osaka Bay has a significant impact on nutrient concentrations in seawater. A tsunami induced by the Nankai Trough earthquake may disturb marine sediments in the inner part of Osaka Bay. An incubation experiment to estimate the release rates of NH4-N and PO4-P was conducted to understand the present conditions and to quantify the changes caused by tsunamis. Two types of cores were created: a "control core" representing the current sediment, and a "redeposition core" representing the redeposition after the tsunami. The release rates have been decreasing since the year 2000 and have remained low. The experimental results suggest that the release rate after exposure to an aerobic environment by a tsunami may decrease to approximately 70% for NH4-N and 60% for PO4-P of the current level. In the past, the release rates were values experienced in the inner part of Osaka Bay. However, the reduction in the release rate by tsunamis may be more limiting for primary production under the current situation where the contribution of release for nutrients in seawater is significant.

This study was aimed at investigating the protective effects of glass ionomer cement (GIC) and surface pre-reacted glass ionomer (S-PRG) fillers used as dental restorative materials on demineralization of bovine enamel. GlasIonomer FX ULTRA (FXU), Fuji IX GP Extra (FIXE), CAREDYNE RESTORE (CDR) were used as GICs. PRG Barrier Coat (BC) was used as the S-PRG filler. They were incubated in a lactic acid solution (pH = 4.0) for 6 d at a temperature of 37 °C. The mineral was etched from the enamel surface, and a large number of Ca and P ions were detected in solution. The Al, F, Na, Sr, and Sr ions were released in GICs and S-RPG fillers. The Zn ion was released only in CDR and the B ion was released only in BC. The presence of apparent enamel prism peripheries was observed after 6 d of treatment for the group containing only enamel blocks. pH values for the FXU, FIXE, CDR, BC, and enamel block groups after 6 d were 6.5, 6.6, 6.7, 5.9, and 5.1, respectively. Therefore, the observed pH neutralization effect suppressed progression of caries due to the release of several ions from the restoratives.

1. Darwin’s naturalization hypothesis predicts that alien species closely related to native species are less likely to naturalize because of strong competition due to niche overlap. Closely related species are likely to attract similar herbivores and to release similar plant volatiles following herbivore attack, thus could attract the same predators. However, the importance of phylogenetic relatedness on the interaction between alien and native plants has never been tested in a multitrophic context. 2. In a mesocosm experiment we grew six alien target plant species alone and in competition with nine native plant species of varying phylogenetic relatedness. To test the effects of multitrophic interactions on the performance of alien target species, we used enclosure cages to expose plants to the presence and absence of herbivorous arthropods, predatory arthropods and nematodes. 3. Surprisingly, biomass and number of flowering structures increased with presence of competitors for some of the alien species, but overall there was no consistent competition effect. Similarly, we found that none of the multitrophic-interaction treatments affected survival, biomass or number of flowering structures of the alien species. 4. We conclude there was no significant relationship between performance measures of the alien species and their phylogenetic relatedness to the native competitors.

This study evaluated gas mixtures of carbon dioxide (CO2) associated with nitrogen (N2) as al-ternatives to the use of CO2 in two phases to improve the welfare of broiler chickens at slaugh-ter. Broilers were exposed to one of three treatments: 40C90C (1st phase: <40% CO2 for 2 min; 2nd phase: >90% CO2 and <2% O2 for 2 min, n=92), 40C60N (40% CO2, 60% N2 and <2% O2 for 4 min, n=79), or 20C80N (20% CO2, 80% N2 and <2% O2 for 4 min, n=72). The time to onset of loss of consciousness (LOC) and death was assessed by brain activity (EEG) and behaviour. Behaviour also allowed characterisation of the aversive response to the treatments. Exposure to 40C60N and 20C80N induced LOC faster (19 s [14 – 30 s] and 21 s [16 – 37 s], respectively) but also with less inter-individual variability compared to 40C90C (53 s [26 – 156 s], P < 0.001) and birds took less time to die (40C60N: 64 s [43 – 108 s]; 20C80N: 70 s [45 – 88 s]; 40C90C: 177 s [89 – 212 s], P < 0.001). The 40C90C birds not only experienced more aversion during induction to LOC but are at risk of remaining conscious when the CO2 concentration is increased in the 2nd phase. From an animal welfare point of view, 40C60N provided the highest welfare, followed by 20C80N and 40C90C.

Bioelectrocatalysis provides the intrinsic catalytic-functions of redox enzymes to non-specific electrode reactions and is the most important and basic concept for biosensors. This review starts by describing fundamental characteristics of bioelectrocatalytic reactions in mediated and direct electron transfer types from a theoretical viewpoint and summarizes amperometric biosensors based on multi-enzymatic cascades and for multi-analyte detection. The review also introduces prospective aspects of two new concepts of biosensors: mass-transfer-controlled (pseudo)steady-state amperometry at microelectrodes with enhanced enzymatic activity without calibration curves and potentiometric coulometry at enzyme/mediator-immobilized biosensors for absolute determination.

Introduction: Tuberculosis (TB) is one of the most prevalent respiratory diseases in the world. In 2020 there were at least 9.9 million new infections, with 1.5 million deaths. Approximately 10% of people infected with Mycobacterium tuberculosis (LTBI) develop the disease during the first 2 to 5 years after infection. Currently in South America, the diagnosis of LTBI continues to be per-formed through the Mantoux tuberculin skin test (TST). Objective: The objective of our study was to compare the sensitivity of a new immunofluorescence IGRA test against a widely available IGRA kit on the market. Material and method: Close contact to infectious patients with TB, or HIV patients or immunocompromised for another cause were recruited. Two interferon gamma release assay (IGRA) diagnostic kits were used and compared with TST. Results: 76 patients were recruited. 93.42% were Chilean nationality, 98.68% of the patients did not have immunosuppres-sion. The sensitivity of the new technique was 88.89% and specificity 92.50% in the study popula-tion compared to the IGRA previously used. In the subgroup older than 36 years, the sensitivity was 95.65% and the specificity 89.47%. Conclusion: IGRA techniques are a new resource in clini-cal laboratories to be able to make an accurate diagnosis in LTBI in the region of the Americas. In our population, the greatest benefit of this new IGRA would be observed in people over 36 years of age, where the sensitivity of the technique was like that of the currently available test.

Bioglasses are highly adoptable bone substitute materials, which can be combined with so-called therapeutic ions. These ions have shown to influence underlying molecular processes of the bone regeneration cascade. Moreover, it is known that bone substitutes induce an immune reaction within their implantation area involving macrophages and their pro- and anti-inflammatory subtypes dependent on their chemical composition. However, only poor knowledge exists regarding the influence of therapeutic ions onto the immune reactions and the associated bone healing. Thus, the aim of this work was to investigate the influence of strontium- and copper-doped bioglasses on the induction of M1- and M2-macrophages as well as the implant bed vascularization. (2) Methods: For this study, two alkali glasses were produced on basis of ICIE-16 bioglass via the melt-quench route with the addition of 5 wt% copper or strontium (ICIE16-Cu and ICIE16-Sr). Pure ICIE16 and 45S5 bioglasses were used as control materials. The bioactivity (ion release), chemical composition and the surface pattern were investigated, as well as an in vivo experiment was performed using the subcutaneous implantation model in rats. (3) Results: SEM imaging showed different formations of hydroxyapatite on the surfaces of the bioglass systems after submersion in simulated body fluid. EDX analysis confirmed the doping process by showing the release kinetics. Copper-doped bioglass exhibited a higher ion release than strontium-doped bioglass. Copper induced both a low immune cell migration and triggered a low number of M1- and M2-macrophages but also of blood vessels. The strontium-containing bioactive glass induced higher numbers of M1-macrophages after 30 days. Both copper- and strontium-doped bioglasses induced comparable numbers of M2-macrophages as found in the control groups. (4) Conclusions: Bioglass doping with copper and strontium did not exhibit significant influence on the foreign body response or the implantation bed vascularization in vivo. However, the prepared bioglass systems seemed to be biocompatible.

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into 4 different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting the novel interventional strategies for metabolic disorders/complications.

Empirical models help us understand the process of plant residue decomposition and nutrient release into the soil. The objective of this study was to determine an appropriate model to describe the decomposition of hairy vetch (Vicia villosa Roth) and cereal rye (Secale cereale L.) cover crop (CC) residue and nitrogen (N) release. Data pertaining to above and belowground CC residue mass loss and N release for up to 2633 cumulative decomposition degree days (112 d) after litterbag installation were obtained from two cropping system experiments, one conducted in 2015 and the other in 2017 and 2018 at the humid subtropical environment of southern IL, USA. Six exponential and two hyperbolic models were fit to percent mass and N remaining data to find the one with minimum Akaike Information Criterion (AIC) and residual sum of squares. Modified three-parameter single exponential and two- or three-parameter hyperbolic models best met the assumed criteria of selection for above and belowground CC residue, respectively. Fitting a double exponential model to a combined data for percent mass and N remaining, which identified two mass and N pools, a fast and a slow pool with different rate constants. A five-parameter double exponential with an asymptote met the preset criteria and passed all tests for normally distributed population, constant variance, and independence of residuals at α = 0.05 when fit to combined data of hairy vetch shoot mass and N remaining. However, a two-parameter hyperbolic and three-parameter asymptotic hyperbolic model provided the best fit to a combined data of cereal rye shoot mass and N remaining, respectively. Both hyperbolic decay models showed a good fit for belowground mass decomposition and N release for both CCs. Cereal rye had poorer fit than hairy vetch for mass and N remaining of both above and belowground mass. The best-selected decay models can be used to estimate the decomposition and N release rates of hairy vetch and cereal rye above and belowground residue in a similar environment.

Renewable resources gain increasing interest as source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014–2018). Special focus is drawn on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.

Abstract Background: Cluster randomized controlled trials are increasingly becoming popular in public health research interventions and health services research in primary health care design and use in low and middle-income countries. However, the majority of researchers in these trials did not account correctly for the effect of confounders and clustering in the design and analysis stages. Objectives: This article aimed to review the main implications of implementing a cluster randomized controlled trials design in public health research and emphasize the practical application of proper analytical methods and the performance of different statistical models. Methods: The practical application of various analytical methods is validated via the utilization of experimental data from a public health research case study. This article also demonstrated the performance of hierarchical models and made comparisons in terms of empirically precise effect size estimates. Results: Three hierarchical statistical models were provided with highly varied effect sizes during the analysis of the intervention effect on outcome, such as model 1 (AOR: 14.32; 95% CI: 3.75–54.68), model 2 (ARR: 3.52; 95% CI: 2.16–5.77), and model 3 (ARR: 4.79; 95% CI: 2.69–5.52).Conclusion: Inaccurate results and potentially misleading conclusions can arise from improper cluster randomized controlled trial designs and analyses. This article has shown that real-world data can be adjusted for the effects of confounders and clustering, and we advocate for the routine use of suitable design and analytical methods. This article concludes that researchers should be careful when selecting hierarchical models to analyze cluster randomized controlled trials.

Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

Background: In this secondary analysis of the Supporting the Modification of Lifestyle In Lowered Emotional States (SMILES) randomised controlled trial, we investigated if the beneficial effects of a dietary intervention on clinical depression were driven, in part, by reducing the consumption of foods classified as ultra-processed.Methods: The SMILES trial enrolled 67 adults with major depressive disorder, randomly assigning them to either a 12-week modified Mediterranean dietary intervention or a social support control. Our analysis included 44 participants with non-missing dietary data and at least one valid Montgomery–Åsberg Depression Rating Scale (MADRS) assessment at 12 weeks of follow-up. The Nova food classification system was used to estimate the proportion of ultra-processed foods in the overall diet (percentage of grams) based on data from seven-day food diaries. We fitted linear regression models under blinded conditions to determine whether ultra-processed food intake-change from baseline to 12 weeks moderated the dietary intervention effects on depressive symptoms. We estimated mean differences in depressive symptoms along with ninety-five per cent confidence intervals (95%CIs).Results: For participants in the dietary intervention, there was an additional 2.5-point improvement in MADRS scores for each 10% reduction in the dietary share of ultra-processed foods compared to participants in the control group (between-group mean differences in depressive symptoms: −2.46, 95%CIs −4.71 to −0.20, p=0.039, η _p ² of 0.10).Conclusions: These preliminary findings suggest that the therapeutic benefit of a dietary intervention for depression may stem, at least in part, from reductions in the dietary share of ultra-processed foods.

Real-world evidence (RWE) is increasingly involved in the early benefit assessment of medicinal drugs. It is expected that RWE will help to speed up approval processes comparable to RWE developments in vaccine research during the COVID-19 pandemic. Definitions of RWE are diverse marking the highly fluid status in this field. So far, RWE comprises information produced from data routinely collected on patient’s health status and/or delivery of health care from various sources other than traditional clinical trials. These sources can include electronic health records, claims, patient-generated data including in home-use settings, data from mobile devices as well as patient, product and disease registries. The aim of the present update was to review the current RWE developments and guidelines mainly in the U.S., the UK, Europe and Germany field during the last decade. RWE has already been included in various approval procedures of regulatory authorities reflecting its actual acceptance and growing importance in evaluating and accelerating new therapies. However, since the RWE research is still in a transition process and since a number of gaps in this field have been explored, more guidance and a consented definition are necessary to increase the implementation of real-world data.

Cancer survival continues to improve in high-income countries, partly explained by advances in screening and treatment. Previous studies have mainly examined the relationship between individual dietary components and cancer prognosis in tumours with good therapeutic response (breast, colon and prostate cancers). The aim of this review was to assess qualitatively (and quantitatively where appropriate) the associations of dietary patterns and cancer prognosis from published prospective cohort studies, as well as the effect of diet interventions by means of randomized controlled trials (RCT). A systematic search was conducted in PubMed, and a total of 35 prospective cohort studies and 14 RCT published between 2011 and 2021 were selected. Better overall diet quality was associated with improved survival among breast and colorectal cancer survivors; adherence to the Mediterranean diet was associated to lower risk of mortality in colorectal and prostate cancer survivors. A meta-analysis using a random-effects model showed that higher versus lower diet quality was associated with a 23% reduction in overall mortality in breast cancer survivors. There was evidence that dietary interventions, generally combined with physical activity, improved overall quality of life, though most studies were in breast cancer survivors. Further cohort and intervention studies in other cancers are needed to make more specific recommendations.

Abstract: Wireless body area networks (WBANs) have strong potential in the field of health monitoring. However, the energy consumption required for accurate monitoring limits the time between battery charges of the wearable sensors, which is a key performance factor (and can be critical in the case of implantable devices). In this paper, we study the inherent trade-off between the power consumption of the sensors and the probability of misclassifying a patient’s health state. We formulate this trade-off as a dynamic problem, in which at each step we can choose to activate a subset of sensors that provide noisy measurements of the patient’s health state. We assume that the (unknown) health state follows a Markov chain, so our problem is formulated as a partially observable Markov decision problem (POMDP). We show that all the past measurements can be summarized as a belief state on the true health state of the patient, which allows tackling the POMDP problem as an MDP on the belief state. We then empirically study the performance of a greedy one-step look-ahead policy compared to the optimal policy obtained by solving the dynamic program. For that purpose, we use an open-source Continuous Glucose Monitoring (CGM) data set of 232 patients over six months and extract the transition matrix and sensor accuracies from the data. We find that the greedy policy saves ~50% of the energy costs while reducing the misclassification costs by less than 2% compared to the most accurate policy possible that always activates all sensors. Our sensitivity analysis reveals that the greedy policy remains nearly optimal across different cost parameters and a varying number of sensors. The results also have practical importance, because while the optimal policy is too complicated, a greedy one-step look-ahead policy can be easily implemented in WBAN systems.

Full-scale/model test comparison studies to validate the traditional ABL wind tunnel simulation technique are reviewed. According to the literature review, notable discrepancies between full-scale measurement results and model test results were observed by most performed comparison studies, but the causes of the observed discrepancies were not revealed in a scientific way by those studies. In this regard, a new research scheme for future full-scale/model test comparison studies is proposed in this article, which utilizes the multiple-fan actively controlled wind tunnel simulation technique. With the new research scheme, future full-scale/model test comparison studies are expected to reasonably disclose the main problems with the traditional ABL wind tunnel simulation technique, and the technique can be improved correspondingly.

Perception of flavor is a dynamic process during which the concentration of aroma molecules at the olfactory epithelium varies with time as they are released progressively from the food in the mouth during consumption. The release kinetics depends on the food matrix itself, but also on food oral processing, such as mastication behavior and food bolus formation with saliva, for which huge inter-individual variations exist due to physiological differences. Sensory methods, such as time-intensity (TI), or the more recent methods temporal dominance of sensations (TDS) and temporal check-all-that-apply (TCATA), are used to account for the dynamic and time-related aspects of flavor perception. Direct injection mass spectrometry (DIMS) techniques that measure in real-time aroma compounds directly in the nose (nosespace), aimed at obtaining data that reflect the pattern of aroma release in real-time during food consumption, supposed to be representative of perception, have been developed since 25 years. Examples obtained with MS operated in chemical ionization mode at atmospheric or sub-atmospheric pressure (atmospheric pressure chemical ionization APCI or proton transfer reaction PTR) will be given, with emphases on studies conducted with simultaneous dynamic sensory evaluation. Inter-individual variations in terms of aroma release and their relevance for understanding flavor perception will be discussed, as well as evidenced cross-modal interactions.

This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

Nowadays, bioeconomy and nanotechnology trends push food packaging sector in the re-placement of food additives by biobased antioxidant/antibacterial compounds and their inclusion in nanocarriers to control their release. Herein by following this trend, a rich in thymol-(TO) activated carbon (AC) nanostructure (TO@AC) was prepared and physiochemically characterized with various technics. This TO@AC nanostructure as well as pure AC were extruded with low density polyethylene (LDPE) to develop novel active packaging LDPE/TO@AC and LDPE/AC films. X-ray diffractometry, Fourier Transform Infrared Spectroscopy and Scanning Electron Microscopy measuraments shown high dispersity and capability of both AC and TO@AC in LDPE matrix which was resulted in enhanced tensile and water/oxygen barrier properties of obtained LDPE/AC and LDPE/TO@AC films. LDPE/TO@AC films shown higher elongation at break values and water/oxygen barrier than LDPE/AC films and significant antioxidant activity. TO release kinetics studies shown that by increasing TO@AC content the total TO amount released increased and the constant release rate decreased. Pork fillets wrapped with the optimum active film containing 15 wt.% TO@AC and succeed to prevent lipid oxidation and heme iron loss during storage. Estimation of microbial population of pork fillets shown that this active film could ex-tend the microbiological shelf-life of pork fillets by 2 days

Films prepared from poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymers produced by Aneurinibacillus sp. H1 using an automatic film applicator were homogeneous and had a defined thickness, which allowed a detailed study of physicochemical properties. Their properties were compared with a poly (3-hydroxybutyrate) homopolymer film prepared by the same procedure, which proved to be significantly more crystalline by DSC and XRD. Structural differences between samples had a major impact on their properties. With increasing 4-hydroxybutyrate content, the ductility and release rate of the model hydrophilic active ingredient increased significantly. Other observed properties, such as the release of the hydrophobic active substance, the contact angle with water and ethylene glycol, or the surface morphology and roughness, were also affected by the composition. The identified properties predetermine these copolymers for wide use in areas such as biomedicine or smart biodegradable packaging for food or cosmetics. The big advantage is the possibility of fine-tuning properties simply by changing the fermentation conditions.

High rates of phosphorus (P) currently being applied to soils for the production of vegetables in the Mekong Delta, Vietnam has led to the concern of its negative effect on the economics and the environment. This research presents a comprehensive study on the determination of P supplying capacity in this region of Vietnam to examine the possibility of reducing P fertilizer input. One hundred twenty (120) soil samples were collected to evaluate total P and Bray 1 available P in the soils. Phosphorus maximum sorption, degree of P saturation, P release, and the effect of P fertilizer on corn (Zea mays L.) yield in greenhouse and fields were also determined. Total P concentrations of 56.7% soil samples evaluated yielded high P concentrations (>560 mg P/kg), while 74.2% of the samples had high Bray 1 available P concentrations (>20 mg P/kg soil). Maximum P sorption ranged from 149 to 555 mg P/kg soil, respectively and has negative correlation to available P (r = - 0.63*), degrees of P saturation ranged from 0.63 to 5.46% correlated to available P (r = 0.98**) and maximum P release ranged from 1.2 to 61.9 mg P/kg soil, respectively correlated to available P (r = 0.96**). Corn grown in soils with available P concentrations >15 mg P/kg did not respond to P fertilizer in greenhouse or field experiments. We conclude that many farmers in this region can reduce P fertilizer input, thus increasing their profits and reducing negative environmental impacts associated with excess soil P for sustainable agriculture.

The radiation-induced optical absorption at 1.5-5.5 eV (up to the beginning of fundamental absorption) has been analyzed in CVD diamond disks exposed to 231-MeV 132Xe ions with four fluences from 1012 to 3.81013 cm-2. The 5-mm diameter samples (thickness 0.4 mm) were prepared by Diamond Materials, Freiburg (Germany), average grain size at growth site was around 80 m, the range of xenon ions was R= 11.5 m. The intensity of several bands grows with ion fluence thus confirming radiation-induced origin of the defects responsible for these bands. The recovery of radiation damage has been investigated via isochronal (stepwise) thermal annealing procedure up to 650°C, while all spectra were measured at room temperature. Based on these spectra, the annealing kinetics of several defects, in particular carbon vacancies (GR1 centers with a broad band 2 eV) and complementary C-interstitial-related defects ( 4 eV), as well as vacancies located nearby nitrogen substitutional atoms (narrow bands around 2.5 eV) have been constructed. The experimental kinetics have also been analyzed in terms of the diffusion-controlled bimolecular reactions. The migration energies of tentatively interstitial atoms (mobile components in recombination process) are obtained, their dependence on the irradiation fluences is discussed.

The new unique technology for granulation of metals and nonmetallic melts is presented in the paper. It was created on the newly developed controlled film flow disintegration with rapid cooling of the droplets and solidified granules in amorphous state. Three new phenomena discovered by us created the base for 3 different methods for granulation of metals and nonmetallic melts in a wide range of granules’ sizes. Electromagnetic resonance method allows producing granules of metals in the range of 1 mm and over. The soliton-like vibrational regime is available for production of any granulation material in the range 0.1-1 mm. Moreover, the shockwave regime is applicable for producing particles from 10 micrometers by size. All methods produce particles of the stated size with a narrow distribution by size: deviation from the average size no more than 50%. The other known methods do not produce granules with such high cooling rate, which can realize the amorphous state and cannot regulate size of particles in such bright but narrow range from 10 micrometers to 1-2 mm.

A novel technique suitable for propulsion of small unmanned aerial vehicles (UAV) is discussed in this paper. This approach utilizes the rotational energy of airborne gyro rotors and converts it into translational propulsion for the vehicle. The energy conversion is achieved by generating precisely directed centrifugal force pulses through short-duration rotor unbalances. The accurate control of the timing and magnitude of these unbalances is crucial for successful propulsion generation. Our first-order theory of controlled unbalance propulsion (CUP) predicts the potential for achieving high translational accelerations and vehicle velocities up to orbital levels. Power saving levitation of UAVs can be attained. In this paper, we provide traceable evidence that pulsed centrifugal propulsion is based on well-established laws of physics and can be realized using state-of-the-art technologies.

This article describes rationales and limitations for making inferences based on data from randomized controlled trials (RCTs). We argue that obtaining a representative random sample from a patient population is impossible for a clinical trial because patients are accrued sequentially over time and thus comprise a convenience sample, subject only to protocol entry criteria. Consequently, the trial’s sample is unlikely to represent a definable patient population. We use causal diagrams to illustrate the difference between random allocation of interventions within a clinical trial sample and true simple or stratified random sampling, as done in surveys. We argue that group-specific statistics, such as a median survival time estimate for a treatment arm in an RCT, have limited meaning as estimates of larger patient population parameters. In contrast, random allocation between interventions facilitates comparative causal inferences about between-treatment effects, such as hazard ratios or differences between probabilities of response. Comparative inferences also require the assumption of transportability from a clinical trial’s convenience sample to a targeted patient population. We focus on the consequences and limitations of randomization procedures in order to clarify the distinctions between pairs of complementary concepts of fundamental importance to data science and RCT interpretation. These include internal and external validity, generalizability and transportability, uncertainty and variability, representativeness and inclusiveness, blocking and stratification, relevance and robustness, forward and reverse causal inference, intention to treat and per protocol analyses, and potential outcomes and counterfactuals.

Demand response flexible loads can provide fast regulation and ancillary services as reserve capacity in power systems. This paper proposes a joint optimization dispatch control strategy for source-load system with stochastic renewable power injection and flexible thermostatically controlled loads (TCLs) and plug-in electric vehicles (PEVs). Specifically, the optimization model is characterized by a chance constraint look-ahead programming to maximal the social welfare of both units and load agents. By solving the chance constraint optimization with sample average approximation (SAA) method, the optimal power scheduling for units and TCL/PEV agents can be obtained. Secondly, two demand response control algorithms for TCLs and PEVs are proposed respectively based on the aggregate control models of the load agents. The TCLs are controlled by its temperature setpoints and PEVs are controlled by its charging power such that the DR control objective can be fulfilled. The effectiveness of the proposed dispatch and control algorithm has been demonstrated by the simulation studies on a modified IEEE 39 bus system with a wind farm, a photovoltaic power station, two TCL agents and two PEV agents.

That how to improve the sensitivity and the detection ability of the Large-caliber sensor is critical to satisfy the requirement of heavy vehicle wear condition monitoring. In this paper, we introduced the LC resonance principle to the design of sensor with large flow channel (7mm). The resonant exciting coil increases the impedance change of the exciting circuit caused by wear particles which magnify the current difference between the two exciting coils and improve the sensitivity of the sensor. The resonant induction coil greatly suppresses the interference signals and magnifies the weak induced electromotive force which is beneficial to enhance the detection ability. In order to boost the detectability for different materials particles, a phase controlled variable-frequency exciting system (PCVFES) was adopted to automatically switch the exciting frequency between 284kHz for ferromagnetic particles and 420KHz for non-ferromagnetic particles. For the weak signal detection, based on the essential characteristic of the signal, we apply a simpler method that modified lock-in amplifier (MLIA) rather than the conventional algorithms (Wavelet transform, EMD). Results show that using these methods the sensitivity and the detection ability of the sensor are significantly improved and the 75μm iron particles and 220μm copper particles were successfully detected which realizes the initial abnormal wear monitoring for the large flow project.

Ante-mortem bovine tuberculosis (bTB) tests for buffaloes include the single comparative intradermal tuberculin test (SCITT), interferon-gamma (IFN-γ) release assay (IGRA) and IFN-γ-inducible protein 10 release assay (IPRA). Although parallel test interpretation increases detection of Mycobacterium bovis-infected buffaloes, these algorithms may not be suitable for screening buffaloes in historically bTB-free herds. In this study, the specificities of three assays were determined using M. bovis unexposed herds, and a high specificity diagnostic algorithm developed. Serial test interpretation using the IGRA and IPRA showed significantly greater specificity (98.3%) than individual tests or parallel testing (73%). When the SCITT was added, the algorithm had a 100% specificity. Since the cytokine assays had imperfect specificity, potential cross-reactivity with nontuberculous mycobacteria (NTM) was investigated. No association was found between NTM presence (in oronasal swab cultures) and positive cytokine assay results. As a proof-of-principle, serial testing was applied to high-value buffaloes (n=153) in a historically bTB-free herd. Buffaloes positive on a single test (n=28) were regarded as test negative. Four buffaloes were positive on IGRA and IPRA, and M. bovis infection was confirmed following culling. These results demonstrate the value of using IGRA and IPRA in series to screen buffalo herds with no previous history of M. bovis infection.

Mitochondrial dysfunctions, e.g. abnormal handling of mitochondrial DNA in TFAM mutants or in altered mitophagy, activate innate immunity. Recent reports also showed that deletion of mitochondrial matrix peptidase ClpP in mice transcriptionally upregulates inflammatory factors. Here, we studied ClpP-null mouse brain at two ages and embryonal fibroblasts, to identify which signaling pathways are responsible, employing mass spectrometry, immunoblots, and reverse transcriptase polymerase chain reaction. Anomalies in the mitochondrial unfolded protein responses pathway were prominent for the co-chaperone DNAJA3, and for its known interactor STAT1. Their mitochondrial dysregulation affected also their extra-mitochondrial abundance, as possible innate immune modulators. Increased expression was observed not only for the transcription factors Stat1/2, but also for two interferon-stimulated genes (Ifi44, Gbp3). Inflammatory responses were strongest for RLR pattern recognition receptors (Ddx58, Ifih1, Oasl2, Trim25) and several cytosolic nucleic acid sensors (Ifit1, Ifit3, Oas1b, Ifi204, Mnda). They can be explained by the accumulation of mitoribosomes and mitochondrial nucleoids in ClpP-null cells, which may act as damage-associated molecular patterns. The consistent dysregulation of these factors from early age might influence also human Perrault syndrome, where ClpP loss-of-function leads to early infertility and deafness, with subsequent widespread neurodegeneration.

SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It produces severe acute respiratory disease (COVID-19), which is fatal in many cases, characterised by cytokine release syndrome (CRS). According to the World Health Organization (WHO), those who smoke are likely to be more vulnerable to infection. Here, in order to clarify the epidemiologic relationship between smoking and COVID-19, we present a systematic literature review until 28 April 2020 and a meta-analysis. It includes 18 recent COVID-19 clinical and epidemiological studies based on smoking patient status from 720 initial studies in China, USA, and Italy. The percentage of hospitalised current smokers was 7.7% (95%CI: 6.9-8.4) in China, 2.3% (95%CI: 1.7-2.9) in the USA and 7.6% (95%CI: 4.2-11.0) in Italy. These percentages were compared to the smoking prevalence of each country and statistically significant differences were found in them all (p <0.0001). By means of the meta-analysis, we offer epidemiological evidence showing that smokers were statistically less likely to be hospitalised (OR=0.18, 95%CI: 0.14-0.23, p<0.01). CRS and exacerbated inflammatory response are associated with aggravation of hospitalise patients. In this scenario, we hypothesise that nicotine, not smoking, could ameliorate the cytokine storm and severe related inflammatory response through the cholinergic-mediated anti-inflammatory pathway.

There are numerous approaches to model an influence of manufacturing parameters on the dissolution and disintegration of solid dosage forms. A modern approach for modelling and simulating complex and heterogeneous systems such as pharmaceutical tablets focuses on computationally-intensive finite-element or discreet element methods. Industrial challenges such as Process Analytical Technology (PAT) and Quality by Design are stimulating computer-based technologies to design, control and improve the quality of pharmaceutical compacts and their performance. In this study the disintegration and dissolution model based on the numerical solutions of the Noyes-Whitney equation and cellular automata supported disintegration model are proposed and evaluated. The results from in vitro release studies of the mefenamic acid formulations were compared to the calculated release patterns from the tablet structures obtained from microtomography experiments and the purely algorithmically created virtual tablets.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

Tuberculosis (TB) associated with diabetes (DM) is a growing problem, particularly in low and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment with isoniazid (INH) or rifampicin (RIF) in people with DM. Participants were assigned six months of INH 300mg/day plus pyridoxine 75mg or three months of RIF 600mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TB preventive treatment is not safe enough to be considered a universal indication to patients with DM and LTBI. These results underline the need to search for alternative TB prevention in DM patients with better safety profiles.

The purpose of this study is to examine the relationship between the institutional investors which can affect financial performance for corporate sustainability on the income smoothing. Therefore, this study focus on the connection between the nature of stock rights and income smoothing in China. For this study, hypotheses were established on the relationship each state-controlled companies, income smoothing, and information equilibrium of individual investors, and empirical analysis was conducted through related variables. The analysis results are summarized in three categories as follows. First, this research finds that state-controlled firms (CONTs) prefer income smoothing activities compared to non-state-controlled firms for the long-term sustainable development of firms using data from 2011 to 2019. Second, this study found out that Institutional investors support the behavior of CONTs to smooth their earnings because this behavior is seen as an attempt by CONTs to convey valuable private information to other investors. Third, we was able to discover that institutional investors' monitoring effect is predominantly driven by pressure-resistant institutional investors. This research complements the lack of empirical research on income smoothing and enable to give a guideline that the type of stock rights is a critical key determinant of participation in income smoothing activities for stable growth and sustainability in the future.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

Modern medicine adopted four presumptions when it evolved from ancient experienced-based mind-body medicine. To understand its failure in finding cures for chronic diseases, we examined four presumptions, and found that statistical population of health properties does not exist for most research purposes, mathematical models are misused to model intensive properties, synthetic drugs are inherently more dangerous than nature-made medicines under their respective application conditions, and reductionist treatments are inferior and inherently dangerous. We found that clinical trials are valid only for research where treatment effect is much stronger than the total effects of all interfering or co-causal factors or errors introduced by misused mathematical models can be tolerated. In all other situations, clinical trials introduce excessive errors and fail to detect treatment effects, or produce biased, incorrect or wrong results. We further found that chronic diseases are manifestation of small departures in multiple process attributes in distinctive personal biological pathways networks, that modern medicine lacks required accuracy for accurately characterizing chronic diseases, and that reductionist treatments are good at controlling symptoms and safe for short term uses. For all stated reasons, as long as modern medicine continues relying on the flawed presumptions, it can never find predictable cures for chronic diseases. By implication, predictable cures to chronic diseases are adjustments to lifestyle, dietary, emotional, and environmental factors to slowly correct departures in process attributes responsible for chronic diseases.

It has become practically impossible to survey the literature on cells derived from adipose tissue with the aim to apply them in regenerative medicine. The aim of this review is to provide a jump start to understanding the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) in regenerative medicine. We show that serious and adequate clinical research demonstrates that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither 'fat stem cells' nor could they exclusively be isolated from adipose tissue, as ADRCs contain the same adult (depending on the definition) pluripotent or multipotent stem cells that are ubiquitously present in the walls of small blood vessels. Of note, the specific isolation procedure used has significant impact on the number and viability of the cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to further separate adipose-derived stem cells (ASCs) from ADRCs if the latter were adequately isolated from adipose tissue. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for manipulating, stimulating and/or (genetically) reprogramming the cells for this purpose. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use.

The difficulties faced by the society in its goal of reducing mortality and improving the health status during the period of the COVID-19 pandemic showed that it is necessary to develop new approaches in the therapy of infectious diseases, leading to higher treatment efficiency and few side effects. The subject of the present study is the formation and characterization of the proper-ties of stable liposomes loaded with extracts from Bulgarian medicinal plants and monitoring their antiviral action against the human strain of coronavirus OC43 (HCoV-OC43) in vitro. The hydrodynamic diameter and -potential of the liposomes containing each type of payload were determined with DLS and electrokinetics. The encapsulated amount of extracts was evaluated against quercetin and gallic acid by using colourimetric methods. The BALB 3T3 Neutral Red Uptake (NRU) phototoxicity/cytotoxicity assay was used to estimate the safety of the compounds. For assessment of the antiviral activity against HCoV-OC43 of liposomes (Lip) containing medicinal plant extracts, the cytopathic effect inhibition test was used. Measurements of the virucidal activity and the effect on the virus adsorption stage was carried out using the endpoint dilution method, and ∆lgs were calculated by comparison with untreated controls. The estimated photo irritation factors (PIF) for the Lip containing extracts were < 2 which assigns them to the category of non-phototoxic substances. When the extracts were introduced into the liposomes as their carriers, the antiviral activity of the vesicles against the replication of HCoV-OC43 in vitro in-creased by several times compared to their individual activity described in our previous study. The determination of the effect of structures loaded with extracts on the extracellular virions and the stage of their adsorption to sensitive HCT-8 cells proved that the liposomes do not affect directly the viral surface or cell membrane, but only perform a function of carriers of the active substances and the observed result is due solely to the intracellular action of the extracts.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

In this work, we report on the first attempt using size-controlled ZnO nanoparticles (NPs) to analyze role of thioacetamide (TAA) in forming ZnS nanostructures from ZnO. The size-controlled B(blue)_, G(green)_, Y(yellow)_ZnO QDs, and NC (nanocrystalline)_ZnO NPs were synthesized by sol-gel process as well as hydrothermal method, respectively and then reacted with an ethanolic TAA solution as sulfur source. After reacting with TAA, the formation of ZnS QDs was observed over time. The chemical reactions were identified using X-ray diffraction (XRD), Transmission Electron Microscope (TEM), UV-vis spectroscopy, and Photoluminescence (PL). All results indicate that ZnS formation is due to direct crystal growth and/or chemical conversion of ZnO to ZnS. Our results enable a broader understanding of the synthetic mechanisms involved in the use of TAA as a sulfur source in forming ZnS nanostructures from ZnO.

Education for Sustainable Development (ESD) is considered vital to the success of the United Nations’ Sustainable Development Goals. Systems Thinking has been identified as a core competency necessary to incorporate into ESD. Systems Thinking orientated ESD learning tools, established methods of assessment of sustainability skills, and studies to demonstrate effectiveness of such learning tools, are all lacking. There is a wealth of experience in the System Dynamics field regarding the application of Systems Thinking and simulation to environmental problems, sustainability and systems education. Many System Dynamicists regard simulation as essential for teaching Systems Thinking. The substantial body of research into the design of effective simulation-based learning environments (SBLEs) can also inform ESD initiatives. This research describes a randomised controlled trial (n=106) to investigate whether an online sustainability learning tool that incorporates Systems Thinking and System Dynamics simulation increases understanding of a specific problem and supports transfer of knowledge to a second problem with a similar systemic structure. The effects of Systems Thinking and simulation were tested separately and in combination. The learning tool was designed for a single online learning session. Simulation was found to increase ESD learning outcomes significantly, and also to support transfer of skills, although less significantly.

The pentose phosphate pathway (PPP) is one of three major pathways involved in glucose metabolism, regulated by glucose-6-phosphate dehydrogenase (G6PD), controlling NADPH formation. NADPH, in turn, regulates the balance of oxidative stress and reactive oxygen species (ROS) levels. G6PD dysfunction, affecting PPP, is implicated in neurological disorders, including epilepsy. However, PPP's role in epileptogenesis and ROS production during epileptic activity remains unclear. To clarify these points, we conducted electrophysiological and imaging analyses on mouse hippocampal brain slices. Using the specific G6PD inhibitor G6PDi-1, we assessed its effects on mouse hippocampal slices, examining intracellular ROS, glucose/oxygen consumption, and ROS production during synaptic stimulation and in the 4AP epilepsy model. G6PDi-1 increased basal intracellular ROS levels and reduced synaptically induced glucose consumption but had no impact on ROS production from synaptic stimulation. In the 4AP model, G6PDi-1 didn't significantly alter spontaneous seizure frequency or H2O2 release amplitude but increased the frequency and peak amplitude of interictal events. These findings suggest that short-term PPP inhibition has a minimal impact on synaptic circuit activity.

Food waste disposal to landfills practice contributes to greenhouse problem due to the emission of gases such as methane to the atmosphere. Shelf-life extension of food products and further valorization of food wastes such as the conversion to activated carbon are tested nowadays as alternative techniques. The development and use of biobased active coatings against food oxidation/bacterial deterioration is an environmentally friendly technique. In this study, a novel food active coating was successfully developed based on a chitosan (CS)/poly-vinyl alcohol (PVOH) matrix activated with a nanohybrid of natural thymol (TO) adsorbed in activated carbon (AC) derived from spent coffee. The results shown that, compared to the pure CS/PVOH polymeric matrix, the coating with 15% wt. TO@AC nanohybrid concentration achieved +23.5 % Young’s modulus value, +20.1% ultimate strength value, increased barrier of +50.2% for water and +74.0 % for oxygen, +69.0% antioxidant activity, increased antibacterial activity of +5.5% against Escherichia coli, +17.8% against Salmonella enterica, +42.5% against Staphylococcus aureus, and +2.5% against Listeria monocytogenes. A visual evaluation of this coating shown a delay to fresh bananas enzymatic browning and significantly decrease their weight loss. This indicates that it could be potentially used to extend the shelf-life of fresh fruits.

Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.

Combustion parameters are the important aspects in the development and research of an internal combustion engines. Hence present work is an attempt to develop an artificial neural network (ANN) model for anticipating the combustion characteristics of computerized CI DI VCR, four strokes, single cylinder, and water cooled engine using mixture of two biodiesel and diesel blends as a fuel. The two biodiesel selected are Jatropha and Simarouba and mixed in the ratio of 75:25. Two biodiesel mixtures is used for the preparation of various blends with diesel. Experiments are carried out at different compression ratio, at different % load and blends B20, B40, B60and neat diesel (B00) fuel to accumulate the assorted combustion data. The input variables are % load, compression ratio, blends and crank angle. The outputs well thought-out are cylinder pressure (CP), net heat release rate (NHRR), cumulative heat release (CHR), rate of pressure rise (RPR), mass fraction burned (MFB) and maximum cylinder pressure. The assessment is focused on developing artificial neural network for the prediction and verifying the combustion characteristics of engine. MATLAB software is used for analysis of different combustion aspects of the engine. Multilayer neural network perceptions are used with Feed-Forward Back Propagation algorithm with performance function for mapping the input and output parameters. The experimental outcomes are compared with ANN estimated results for the analysis. The outcome from the study authenticate that experimental results are in match with ANN results. The accuracy of the ANN model shows the developed model can effectively predict the engine combustion characteristics with excellent regression coefficients ‘R’ and its values are close to unity and the mean square errors are extremely less. ANN model approach is competent towards predicting the combustion aspect of diesel engine with good accuracy

Keywords: Requirements prioritization, Next release plan, Software product planning, Decision support, MoSCoW, AHP, K-Menas, GMM, BIRCH, PAM, Hierarchical, Clustering, Clusters Evaluation

AbstractIntroduction: Increasing knowledge of obstetric danger signs (ODS) and encouraging birth preparedness and complication readiness (BPCR) practices are strategies to increase skilled maternal health service utilization in low-income countries. One of the methods to increase mothers' knowledge about ODS and promote BPCR practice is through health education intervention (HEI). However, the effect of context-specific community-based health education led by women's groups on these outcomes has not been comprehensively studied, and the existing evidence is inconclusive. Thus, we aimed to evaluate the effect of a context-specific community-based HEI led by women's groups on mothers' knowledge regarding ODS and BPCR practices in southern Ethiopia.Methods: An open-label, two-arm parallel group cluster-randomized controlled trial was conducted from January to August 2023 on pregnant women from 24 clusters (kebeles) (12 interventions and 12 controls) in the northern zone of the Sidama region. The Open Data Kit smartphone application was utilized to collect data. The intention-to-treat analysis was used to compare outcomes between groups. We fitted multi-level mixed-effects modified Poisson regression with robust standard error to account for between and within cluster effects. Results: One thousand and seventy pregnant women (540 in the intervention and 530 in the control clusters) responded to this study, making the overall response rate 95.02%. Excessive vaginal bleeding (94.3% in the interventional group vs. 88.7% in the control group) was the commonest ODS mentioned during childbirth. Overall, 68.7% of women in the intervention group and 36.2% of mothers in the control group had good knowledge of ODS (P-value < 0.001). Saving money and materials (97.1% in the interventional group vs. 92.7% in the control group) was the most frequently practiced BPCR plan. Overall, 64.3% of women in the intervention group and 38.9% of mothers in the control group practiced BPCR (P-value < 0.001). HEI significantly increased overall knowledge of ODS (adjusted risk ratio [ARR]: 1.71; 99% CI: 1.14-2.57) and improved overall BPCR practice (ARR: 1.55; 99% CI: 1.02-2.39). Conclusions: A community-based HEI led by women's groups improved mothers' knowledge regarding ODS and BPCR practices in a rural setting in southern Ethiopia. Interventions designed to increase women's knowledge of ODS and improve BPCR practice must implement context-specific, community-based HEI that aligns with World Health Organization recommendations. Trial registration: NCT05865873

Breast cancer is the most common malignant disease in women. Preclinical studies have confirmed that the local anesthetic levobupivacaine has a cytotoxic effect on breast cancer cells. We examined whether postoperative wound infiltration with levobupivacaine influences survival in 120 patients who were operated on for breast cancer and underwent quadrantectomy or mastectomy with axillary lymph node dissection. Groups with continuous levobupivacaine wound infiltration, bolus wound infiltration, and diclofenac analgesia were compared. Long-term outcomes examined were quality of life, shoulder disability, and hand grip strength (HGS) after one year, and survival after 5 and 10 years. Groups that had infiltration analgesia had better shoulder function compared to diclofenac after one year. Levobupivacaine PCA group had the best preserved HGS after 1 year (P=0.022). The most significant predictor of the 5-year outcome was HGS (P=0.03). Although the best survival after 5 and 10 years was registered in the bolus levobupivacaine group, statistical significance was not reached (P=0.36). The extent of the disease at the time of surgery is the most important predictor of long-term survival. A larger prospective clinical study could better confirm the effect of levobupivacaine wound infiltration on outcomes after breast cancer surgery observed in this pilot study. Trial number NCT05829707

: Seasonal influenza (a.k.a flu) is responsible for considerable morbidity and mortality across the globe. The three recognized pathogens that cause epidemics during the winter season are influenza A, B and C. The influenza virus is particularly dangerous due to its mutability. Vaccines are an effective tool in preventing seasonal influenza, and their formulas are updated yearly according to WHO recommendations. However, in order to facilitate decision-making in the planning of the intervention, policymakers need information on the projected costs and quantities related to introducing the influenza vaccine, in order to help governments obtain an optimal allocation of the vaccine each year. In this paper, an approach based on a Controlled Elitism Non-Dominated Sorting Genetic Algorithm (CENSGA) model is introduced to optimize the allocation of influenza vaccination. A bi-objective model is formulated to control the infection volume, and reduce the unit cost of the vaccination campaign. An SIR (Susceptible–Infected–Recovered) model is employed for representing a potential epidemic. The model constraints are based on the epidemiological model, time management, and vaccine quantity. A two-phase optimization process is proposed: guardian control followed by contingent controls. The proposed approach is an evolutionary metaheuristic multi-objective optimization algorithm with a local search procedure based on a hash table. Moreover, in order to optimize the scheduling of a set of policies over a predetermined time to form a complete campaign, an extended CENSGA is introduced with a variable-length chromosome (VLC) along with mutation and crossover operations. To validate the applicability of the proposed CENSGA, it is compared with the classical Non-Dominated Sorting Genetic Algorithm (NSGA-II). The results are analyzed using graphical and statistical comparisons in terms of cardinality, convergence, distribution and spread quality metrics, illustrating that the proposed CENSGA is effective and useful for determining the optimal vaccination allocation campaigns.

In this paper, we study the performance of various deep reinforcement learning algorithms to enhance the energy management system of a microgrid. We propose a novel microgrid model that consists of a wind turbine generator, an energy storage system, a set of thermostatically controlled loads, a set of price-responsive loads, and a connection to the main grid. The proposed energy management system is designed to coordinate among the different flexible sources by defining the priority resources, direct demand control signals, and electricity prices. Seven deep reinforcement learning algorithms were implemented and are empirically compared in this paper. The numerical results show that the deep reinforcement learning algorithms differ widely in their ability to converge to optimal policies. By adding an experience replay and a semi-deterministic training phase to the well-known asynchronous advantage actor-critic algorithm, we achieved the highest model performance as well as convergence to near-optimal policies.

I propose a new strategy to suppress human cancer completely with two entirely new drug compounds exploiting cancer's Warburg effect characterized by a defective mitochondrial aerobic respiration, substituted for by cytosolic aerobic fermentation/glycolysis of D-(+)-glucose into L-(+)-lactic acid. The two essentially new drugs compound 1 [P(op)T(est)162] and compound 3 (PT167) represent new highly symmetric, four-bladed propeller-shaped polyammonium cations. The in vitro antineoplastic highly efficacious drug compound 3 represents a covalent combination of compound 1 and compound 2 (PT166). The intermediate drug compound 2 is an entirely new colchic(in)oid derivative synthesized from colchicine. Compound 2's structure was determined by X-ray crystallography. Compound 1 and compound 3 were active in vitro versus 60 human cancer cell lines of the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer cell testing. Compound 1 and compound 3 both not only stop the growth of cancer cells to ±0% (cancerostatic effect), but completely kill nearly all 60 cancer cells to a level of almost −100% (tumoricidal effect). Compound 1 and compound 3 induce mitochondrial apoptosis (under cytochrome c release) in all cancer cells tested by (re)activating (in most cancers impaired) p53 function which results in a decrease of cancer's dysregulated cyclin D1 and an induction of the cell cycle-halting cyclin-dependent kinase inhibitor p21^Waf1/p21^Cip1.

(1)Background: Among new anti-angiogenetic agents being developed and everchanging guidelines indications, the question of benefits/safety ratio remains unclear. (2)Methods: we have conducted a systematic review and meta-analysis of 25 randomized controlled trials (15487 patients), evaluating overall survival – OS, progression free survival– PFS and toxicity (grade ≥3 adverse effects, type and number of all adverse effects. (3)Results: analysis showed improvement of pooled-PFS (HR 0.72, 95%CI 0.66–0.78, I2 = 77%, P<0.00001) regardless of treatment settings (first-line - HR 0.83, 95%CI 0.77-0.90, P<0.00001, recurrent cancer – HR 0.61, 95%CI 0.54-0.68, P<0.00001 or maintenance – HR 0.82, 95%CI 0.67-1.00, P=0.04) and type of anti-angiogenetic drug used (VEGF inhibitors, VEGF-R inhibitors or angiopoietin inhibitors). Improved OS was also observed (HR 0.95, 95%CI 0.91–0.99, P=0.02). OS benefits were only observed in recurrent platinum-sensitive or platinum-resistant cancers. Grade≥3 adverse effects were increased across all trials. Anti-angiogenetic therapy increased the risk of hypertension, infection, thromboembolic/ hemorrhagic events, gastro-intestinal perforations but not the risk of wound related issues, anemia or posterior leukoencephalopathy syndrome. (4)Conclusions: Although angiogenesis inhibitors improve PFS, there is little to no OS benefits. Given the high risk of severe adverse reactions a careful selection of patients is required for obtaining the best results possible.

With the advent of COVID19, the attitude of health authorities around the world, led mainly by the West, demanded a level of proof as evidence for cheap, non-patented remedies while promoting expensive, patented, and untested remedies by using emergency use authorization and special provisions afforded to the status of a pandemic emergency. Western science has neither a tested nor a valid historical basis of a logical system that informs to authenticate scientific practices. Here we use a logical heuristic derived from ancient Buddhist logic, which is consistent with the conduct of modern science. We applied the heuristic to show that enough evidence was available for using cost-effective early therapies such as vitamin D supplementation as a public health measure during the first half of 2020. Strong supporting evidence has since accumulated. Apart from political and financial decisions incompatible with science and other conflicts of interest, a critical barrier to evaluating and approving early therapies appears to be the fallacy that the randomized controlled trial (RCT) is the superior proof method in medical hypotheses, including those for nutrients. Logically, no reason exists why properly designed retrospective, ecological, and naturalistic studies with adequate sample sizes and applied appropriate statistical methods would not be as valid as RCTs, especially when elucidating a causative factor instead of treatment. That assertion is particularly true for nutrient deficiencies, interventions, and other cost-effective therapies. Leading health authorities’ failure or refusal to consider other study types (because of either poor logic or vested interest) probably contributed to the spread of misinformation, symptomatic disease, complications, and deaths from COVID19. Partial immunity derived from vaccines and the later development of more contagious variants—and thus a sense of acceptance that SARS-CoV-2 had progressed from a pandemic to an endemic—shows the hollowness of the initial promotions and mandates of vaccines as a cure. Adequate knowledge was available in 2020 to advise that SARS-CoV-2 will continue to mutate, with variants emerging a few times per year, making the vaccine less effective. Emerging evidence confirms that natural immunity better protects against new variants than vaccination against the spike protein. Had vitamin D been adopted as part of the public health measure through a broader supplementation program in 2020 or even today (through sun exposure or as a prophylactic or adjunct therapy early on), the viral spread and symptomatic disease may have been suppressed, with minimal lockdowns and quarantine, and economic harm. The pandemic could have been halted with a significantly reduced need for hospitalization, complications, and deaths, potentially saving millions of lives.

Chronoamperometric curves of the oxidation of a ferrocenyl derivative by the potential step showed diffusion controlled-like currents less than the Cottrell's equation at a platinum wire electrode. The lower deviation cannot be explained by the Butler-Volmer heterogeneous kinetics, but was ascribed to the negatively capacitive current associated with the redox reaction. The deviation at the fully oxidized potential corresponds to the non-zero concentration at the electrode surface, which cannot be predicted from the Nernst equation. The Nernst equation expresses the relationship of the potential with the activity at the electrode surface rather than the concentration. The diffusion equation provides the relation of the current with the surface concentration rather than the activity. The negative capacitance or the non-zero concentration may arise from structure formation on the electrode owing to the dipole-dipole interaction, which is similar to the generation of the double layer capacitance including frequency dispersion. On this concept, we derive here expressions for the lowered diffusion-controlled current and the time-dependent surface concentration. The negatively capacitive current shows the time-dependence of t-0.9, which is similar to the decay of the double layer capacitive currents. The surface concentration decays with the t-0.4-dependence.