E2F4 was initially described as a transcription factor with a key function in the regulation of cell quiescence. Nevertheless, a number of recent studies have established that E2F4 can also play a relevant role in cell and tissue homeostasis as well as tissue regeneration. For these non-canonical functions, E2F4 can also act in the cytoplasm, where it is able to interact with many homeostatic and synaptic regulators. Since E2F4 is expressed in the nervous system, it may fulfill a crucial role in brain function and homeostasis, being a promising multifactorial target for neurodegenerative diseases and brain aging. The regulation of E2F4 is complex as it can be chemically modified through acetylation, from which we present evidence in the brain, as well as methylation, and phosphorylation. The phosphorylation of E2F4 within a conserved threonine motif induces cell cycle re-entry in neurons, while a dominant negative form of E2F4 (E2F4DN), in which the conserved threonines have been substituted by alanines, has been shown to act as a multifactorial therapeutic agent for Alzheimer’s disease (AD). We have generated transgenic mice neuronally expressing E2F4DN. We have recently shown using this mouse strain that expression of E2F4DN in 5xFAD mice, a known murine model of AD, improved cognitive function, reduced neuronal tetraploidization, and induced a transcriptional program consistent with modulation of amyloid-beta (Abeta) peptide proteostasis and brain homeostasis recovery. 5xFAD/E2F4DN mice also showed reduced microgliosis and astrogliosis in both cerebral cortex and hippocampus at 3-6 months of age. Here we have analyzed the immune response in 1 year-old 5xFAD/E2F4DN mice, concluding that reduced microgliosis and astrogliosis is maintained at this late stage. In addition, the expression of E2F4DN also reduced age-associated microgliosis in wild-type mice, thus stressing its role as a brain homeostatic agent. We conclude that E2F4DN transgenic mice represent a promising tool for the evaluation of E2F4 as a therapeutic target in neuropathology and brain aging.

Pancreatic cancer represents one of the difficult problems of contemporary medicine. The development illness evolves very slowly, takes place in special sake (stroma) and manifests clinically close to a final stage. Another feature of this pathology is a coexistence (symbiotic) effect between cancer cells and normal cells inside stroma. All these aspects make it difficult to understand the pathogenesis of pancreatic cancer and develop a proper therapy. The emergence of pancreatic pre-cancer and cancer cells represents a branching stochastic process engaging populations of 64 cells differing in the number of acquired mutations. In this study we formulate and calibrate the mathematical model of pancreatic cancer using the quasispecies framework. The mathematical model incorporates the mutation matrix, fineness landscape matrix and the death rates. Each element of the mutation matrix presents the probability of appearing a specific mutation in the branching sequence of cells representing the accumulation of mutations. The model incorporates the cancer cell elimination by effect CD8 T cells (CTL). The down-regulation of the effector function of CTLs and exhaustion are parameterized. The symbiotic effect of coexistence of normal and cancer cells is considered. The computational predictions obtained with the model are consistent with empirical data. The modelling approach can be used to investigate other types of cancers and examine various treatment procedures.

Traditional Health Practitioners (THPs) are considered as the entry level of care in African societies and play an important role in the delivery of health services to the population. A phenomenological qualitative study was carried out among pur-posefully selected THPs in Mthatha to understand their roles and the challenges they face in providing maternal health services. The study included a focus group discussion with seven participants, which yielded three themes and seven sub-themes. The content analysis of descriptive data from the focus group discussion revealed threats posed by unregistered and counterfeit THPs to the lives of pregnant women in rural settings. THPs' wide range of services allowed pregnant women to receive prenatal, antenatal, and postnatal care in close proximity. This level of care, however, was characterized by high levels of secrecy and counterfeit practitioners who used human body parts, which jeopardized the practice and made it unpopular. Traditional health practice must be protected through registration of THPs and the establishment of functional referral pathways between THPs and conventional health services.

Objectives: COVID-19 pandemic interrupted the Spanish professional football competition until May 2020, when it was restarted following a surveillance protocol established by LaLiga. The aims were to describe the infective and serological status of professional football players (PLY) and staff (STF) between May 5th 2020 until April 22nd 2021, to analyze the spatial-temporal distribution of the COVID-19 disease in this cohort and its comparison to the Spanish population. Methods: a prospective observational cohort study was carried out. Differences between PLY and STF were assessed by Chi-squared test and test of equality of proportions. Pearson correlation test was used to measure the presence of an association between the percentages of positivity in population and LaLiga cohort. Results: 137,420 RT-PCR and 20,376 IgG serology tests were performed in 7,112 professionals. Positive baseline serology was detected in 10.57% of PLY and 6.38% of STF. Among those who started the follow-up as not infected and before STF vaccination, 11.87% of PLY and 5.03% of STF became positive. Before summer 2020 the prevalence of infection was similar than the observed at national level. The percentage of positivity in the Spanish population was higher than in LaLiga cohort, but both series showed a similar decreasing trend.

In this study, we describe quark confinement in terms of linear interaction potentials and solve the problem of the net spin of a proton. The three quarks in a proton are assumed to revolve around a common center, and their masses are determined assuming they are Dirac particles. On the basis of these assumptions, the magnetic moment of a proton can be derived. Moreover, the rotation of the quarks is considered, in which an electrical current induces a magnetic field. Thus, the scalar product of the magnetic moment and field describes the linear interaction potential between the quarks, and the mass of the proton can be obtained. The proton mass predicted by this physical model is consistent with experimental values, and no numerical or fitting calculations are required. Furthermore, using the newly derived spins and angular momentum of the three quarks, we derived the net spin of a proton. Additionally, we predicted the mass of a pi-meson from the same model, which agrees with the experimental values.

Dengue Fever (DF) is an important arthropod-borne viral infection, which has repeatedly oc-curred as outbreaks in eastern and northeastern Ethiopia since 2013. A cross-sectional epidemio-logical outbreak investigation was carried out from September - November 2019 on febrile pa-tients (confirmed malaria negative) who presented with suspected and confirmed DF at both public and private health facilities in Gewane District, Afar Region, northeastern Ethiopia. Ento-mological investigation of containers found in randomly selected houses belonging to DF positive patients was undertaken, to survey for the presence of Aedes larvae or pupae. A total of 1185 DF cases was recorded from six heath facilities during the 3-month study period. The mean age of DF cases was 27.2 years and 42.7% of the cases were female. The most affected age group was 15-49 years (78.98%). However, the attack rate (AR) was highest in the 49+ age group (134.2). A total of 162 artificial containers were inspected from 62 houses, with 49.4% found positive for Aedes larva/pupae. Aedes mosquitoes were mostly found breeding in buckets/bowls, clay jars, plastic tanks, and tires. World Health Organization entomological indices classified the study site as high risk for dengue outbreaks (House Index=45.2%, Container Index=49.4% and Breteau In-dex=129). Study findings highlight the importance of vector control to prevent future dengue out-breaks in the region. The scarcity of drinking water and changing climactic conditions may have also contributed to the occurrence of this outbreak.

An ongoing monkeypox outbreak in non-endemic countries has resulted in the declaration of a Public Health Emergency of International Concern by the World Health Organization (WHO). Though monkeypox has long been endemic in regions of Sub-Saharan Africa, relatively little is known about its ecology, epidemiology, and transmission. Here, we consider the relevant research on both monkeypox and smallpox, a close relative, to make inferences about the current outbreak. Undetected circulation, combined with atypical transmission and case presentation, including mild and asymptomatic disease, have led to the spread of monkeypox in non-endemic regions. Broader availability of diagnostics, enhanced surveillance, and targeted education, combined with a better understanding of the routes of transmission, are critical to identify at-risk populations and design science-based countermeasures to control the current outbreak.

Deep Learning (DL) and Machine Learning (ML) are widely used in many fields, but rarely used in Frequency Estimation (FE) and Slope Estimation (SE) of signals. Frequency and slope estimation for Frequency-Modulated (FM) and single-tone sinusoidal signals are essential in various applications, such as wireless communications, sonar, and radar measurements. In this work, artificial neural network (ANN) and convolutional neural network (CNN) are used in frequency and slope estimation for FM signals under Additive White Gaussian Noise (AWGN) and Additive Symmetric alpha Stable Noise (SαSN). SαS distributions are impulsive noise disturbances found in many communication environments like marine systems; their distribution lacks a closed-form Probability Density Function (PDF), except for specific cases, and infinite second-order statistic, hence Geometric SNR (GSNR) is used in this work to determine the impulsiveness of noise in a mixture of Gaussian and SαS noise processes. ANN is a machine learning classifier, designed with few layers for reducing FE and SE complexity while getting higher accuracy as compared with classical techniques. CNN is a deep learning classifier, designed with many layers for FE and SE, and proved to be more accurate than ANN when dealing with big data and finding optimal features. Simulation results show that SαS noise can be much more harmful for FE and SE of FM signals than Gaussian noise. DL and ML can significantly reduce FE complexity, memory cost, and power consumption, which is important in many systems such as some Internet of Things (IoT) sensor applications. After training DCNN for frequency and slope estimation of LFM signals, the performance of DCNN (in terms of accuracy) can give acceptable results at very low signal-to-noise ratios where TFD fails, giving more than 20dB difference in the GSNR working range.

As a mediator variable, self-confidence is one of the most effective elements of the decision-making process of consumer behaviour. This research has studied the effects of different aspects of consuming fashion on the self-confidence and behaviour of consumers in Tehran’s clothing market. This study has considered the acceptance of new products, interest in mode and fashion, utilitarianism, and personal taste in its analysis. This research aims to understand the fashion buying behaviour amongst Iranian consumers in consideration of their attitude towards self-confidence and aspects of fashion consumption. The statistic sample is 400 consumers from Tehran’s clothing market who have been chosen based on the random availability procedure. The primary tool in this research was a questionary used to testify the assumptions and a model fit created by using structural equations and factor analysis. This research showed that the interest in mode and fashion, personal taste, utilitarianism, and new products positively impact self-confidence. In addition, the positive impact of self-confidence on fashion buying behaviour was confirmed.

Traumatic cardiac arrest has a high mortality. We report the case of a 65 years old women who presented a cardiac arrest following traffic accident. Examinations concluded to a tension gastro thorax with a delayed diagnosis. Naso gastric tube insertion was for many authors a temporary care while waiting for surgery. We report on the diagnostic difficulties found in the literature and a recent review of published cases.

Objectives: This study assessed the associations between parent intent to have their child receive COVID-19 vaccination, and demographic factors and various child activities including attendance at in-person education or childcare. Methods: Persons undergoing COVID-19 testing residing in Minnesota and Los Angeles County, California with children aged <12 years completed anonymous internet-based surveys between May 10 and September 6, 2021 to assess factors associated with intention to vaccinate their child. Factors influencing parents’ decision to have their child attend in person school or childcare were examined. Estimated adjusted odds rations (AORs, 95% CI) were computed between parents’ intentions regarding children’s COVID-19 vaccination and participation in school and extra-curricular activities using multinomial logistic regression. Results: Compared to parents intending to vaccinate their children (n=4,686 [77.2%]), those undecided (n=874 [14.4%] or without intention to vaccinate (n=508 [8.4%]) tended to be younger, non-White, less educated and themselves not vaccinated against COVID-19. Their children more commonly participated in sports (aOR:1.51 1.17-1.95) and in-person faith or community activities (aOR:4.71 (3.62-6.11). They further indicated that additional information regarding vaccine safety and effectiveness would influence their decision. COVID-19 mitigation measures were the most common factors influencing parents’ decision to have their child attend in-person class or childcare. Conclusions: Several demographic and socioeconomic factors are associated with parents’ decision whether to vaccinate their <12-year-old children for COVID-19. Child participation in in-person activities was associated with parents’ intentions not to vaccinate. Tailored communications may be useful to inform parents’ decisions regarding safety and effectiveness of vaccination.

Law of conservation of energy is the most well-established law of modern physics. But, inflationary cosmological model which assumes the universe to be created from a point of singularity has not been able to identify the source of energy for creation of this universe. As per uncertainty principle, a quantum vacuum fluctuation can at most create energy of ~10^-8 kg in a Planck time of ~5.4 ×10^-44 s whereas total positive energy due to matter/vacuum existing in the universe is more than ~10⁵⁴ kg. To solve this problem, we have recently published a new cosmological model (Biswaranjan Dikshit, Canadian Journal of Physics, 100, 218-225, [2022]) in which we have mathematically proved that the total energy of the universe can be zero right from the beginning of the universe to till date due to negative gravitational potential energy and thus law of conservation of energy can be satisfied during creation of the universe from nothing. In this article, starting from a simple argument, we explain why net energy of the universe can be zero only in our model, not in standard cosmological model. An interesting fact pointed out in this paper is that the factor ~10⁶² by which radius of universe has increased from its starting value of ~10^-36 m to present value of ~10²⁶ m is same as the factor by which positive energy has increased from Planck energy ~10^-8 kg to present value ~10⁵⁴ kg. This is in agreement with our new model that predicts the positive energy of universe to be proportional to the radius of universe. We also bring out to the notice that zero energy universe is possible only if smallest possible length in nature is, l_min=l_p(π/2)^1/2 = 2.0×10^-35 m. Minimum possible length is important in theory of quantum gravity and string theory.

Land Use Land Cover (LULC) change and urban growth have a significant influence on local climate of cities. From 1985 to 2021 the population of Baghdad increased by 103%. Therefore, the risen question is how this expansion influences the temperature of the city. The study aims to identify urban growth of Baghdad, investigate its influence on variation of Land Surface Temperature (LST) and identify the main factors that control the surface temperature of the city. Three Landsat images from 1985 to 2021, in addition to sixteen potential factors, were used in the study. Our findings suggest that during the study period, vegetated areas declined by 39% while built-up class increased by 139%. Bare soil recorded the highest surface temperature. The study found that surface temperature has a strong inverse relationship with vegetation (Normalized Difference Vegetation Index (NDVI): r = -0.62, p < 0.001) and moisture (Normalized Difference Moisture Index (NDMI): r = -0.65, p < 0.001). Therefore, increasing vegetation and water body lead to decrease temperature of the city. Our findings help policymakers to deal with climatic issues rising from urban growth of the city.

The enormous increase in the volume of Earth Observations (EOs) has provided the scientific community with unprecedented temporal, spatial, and spectral information. However, this increase in the volume of EOs has not yet resulted in proportional progress with our ability to forecast agricultural systems.This study examines the applicability of EOs obtained from Sentinel2 and Landsat8 for constraining the APSIM-Maize model parameters. We leveraged leaf area index (LAI) retrieved from Sentinel2 and Landsat8 NDVI to constrain a series of APSIM-Maize model parameters in three different Bayesian multi-criteria optimization frameworks across 13 different sites across the U.S Midwest. A time variant sensitivity analysis was performed to identify the most influential parameters driving the LAI estimates in APSIM-Maize model. Then surrogate models were develop using random samples taken from the parameter space using Latin hypercube sampling to emulate APSIM’s behavior in simulating NDVI and LAI at all sites. Site-level, global and hierarchical Bayesian optimization models were then developed using the site-level emulators to simultaneously constrain all parameters and estimate the site to site variability in crop parameters. For within sample predictions, site-level optimization showed the largest predictive uncertainty around LAI and crop yield, whereas the global optimization showed the most constraint predictions for these variables. Lowest RMSE for within sample yield prediction was found for hierarchical optimization scheme (1423 Kg ha−1) while the largest RMSE was found for site-level (1494 Kg ha−1). In out-of-sample predictions within the spatio-temporal extent of the training sites, global optimization showed lower RMSE (1627 Kg ha−1) compared to the hierarchical approach (1822 Kg ha−1) across 90 independent sites in the U.S Midwest. On comparison between these two optimization schemes across another 242 independent sites outside the spatio-temporal extent of the training sites, global optimization also showed substantially lower RMSE (1554 Kg ha−1) as compared to the hierarchical approach (2532 Kg ha−1). Overall, EOs demonstrated their real use case for constraining process-based crop models and showed comparable results to model calibration exercises using only field measurements.

Mutations within the hepatitis B virus (HBV) genome have been associated with rapid progres-sion to hepatocellular carcinoma (HCC); however, there is limited information regarding the prevalence and impact of these mutations in most of sub-Saharan Africa, including Botswana. We aimed to determine the prevalence of HBV mutations known to be associated with progression to HCC using a retrospective, cross-sectional analysis of 48 previously generated HBV sequences from adults with concomitant HBV/HIV initiating HIV antiretroviral therapy in Botswana. The sequences were aligned with reference sequences, and HCC-associated mutations were manually identified using BioEdit. Sixteen (33.3 %) of 48 participant samples had 20 HCC-associated mu-tations. Seven HCC mutations were present in the core region, 4 in the preCore region, 7 in the X region, and one mutation in the surface region, as well as deletions within the preSurface 1 region. Seven of the 16 participants (43.8%) had multiple HCC-associated mutations. There were also previously uncharacterized mutations at positions with known HCC-associated mutations. HCC-associated mutations were common in this cohort; hence, some participants may require close clinical monitoring as they might be more prone to rapid disease progression. Other functionally uncharacterized polymorphisms were also detected and require characterization in future studies.

Drought is one of the most serious abiotic stressors in the environment, restricting agricultural production by reducing plant growth, development, and productivity. To investigate such a complex and multifaceted stressor and its effects on the plants, a systems biology-based approach is necessitated, entailing the generation of co-expression networks, identification of highly-priority transcription factors (TFs) dynamic mathematical modeling, and computational simulations. Here, we studied a high-resolution drought transcriptome of Arabidopsis. We revealed distinct temporal transcriptional signatures and demonstrated the involvement of specific biological pathways. Generation of a large-scale co-expression network followed by network centrality analyses identified 117 TFs that possess critical properties of hubs, bottlenecks, and high clustering coefficients nodes. Dynamic transcriptional regulatory modeling on integrated TF-target and transcriptome datasets uncovered major transcriptional events during the course of drought stress. Mathematical transcriptional simulations allowed us to ascertain the activation status of major TFs as well as the transcriptional intensity and amplitude of their target genes. Finally, we validated our predictions by providing experimental evidence of gene expression under drought stress for a set of four TFs and their major target genes using qRT-PCR. Taken together, we provided a systems-level perspective on the dynamic transcriptional regulation during drought stress in Arabidopsis and uncovered numerous novel TFs that can potentially be used in future genetic crop engineering programs.

Carbazole is one of the typical heterocyclic aromatic compounds (NSO-HETs) observed in pol-luted urban atmosphere, which has become a serious environmental concern. The most im-portant atmospheric loss process of carbazole is the reaction with OH radical. The present work investigated the mechanism of OH-initiated atmospheric oxidation degradation of carbazole by using density functional theory (DFT) calculations at the M06-2X/6-311++G(3df,2p)//M06-2X/6-311+G(d,p) level. The rate constants were determined by the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The lifetime of carbazole determined by OH was compared with other typical NSO-HETs. The theoretical results show that the degradation of carbazole initiated by OH radical includes four types of reactions: OH additions to “bend” C atoms, OH additions to “benzene ring” C atoms, H abstractions from C-H bonds and the H ab-straction from N-H bond. The OH addition to C1 atom and the H abstraction from N-H bond are energetically favorable. The main oxidation products are hydroxycarbazole, dialdehyde, carba-zolequinone, carbazole-ol, hydroxy-carbazole-one and hydroperoxyl-carbazole-one. The calcu-lated overall rate constant of carbazole oxidation by OH radical is 6.52 × 10−12 cm3 molecule−1 s−1 and the atmospheric lifetime is 43.92 h under the condition of 298 K and 1 atm. The lifetime of carbazole determined by OH radical is similar with that of dibenzothiophene oxidation but longer than those of pyrrole, indole, dibenzofuran and fluorene. This work provides a better understanding of the reactivity of carbazole in the atmospheric environment, the formation of secondary organic aerosols, and the chemical degradation and removal of carbazole in the at-mospheric environment.

ABSTRACT Background It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under- or over-treatment. Deep Neural Network (DNN) learning, commonly referred to as deep learning, has become popular due to its success in image detection and prediction, but questions such as whether deep learning outperforms other machine learning methods when using non-image clinical data remain unanswered. Grid search has been introduced to deep learning hyperparameter tunning for the purpose of improving its prediction performance, but the effect of grid search on other machine learning methods are under-studied. In this research, we take the empirical approach to study the performance of deep learning and other machine learning methods when using non-image clinical data to predict the occurrence of breast cancer metastasis (BCM) 5, 10, or 15-years after the initial treatment. We developed DNN models as well as models using 9 other machine learning methods including Naive Bayes (NB), Logistic Regression (LR), Support Vector Machine (SVM), LASSO, Decision Tree (DT), k-Nearest Neighbors (KNN), Random Forrest (RF), AdaBoost (ADB), and XGBoost (XGB). We used grid search to tune hyperparameters for all methods. We then compared the deep learning models to the models trained using the 9 other machine learning methods. Results Based on the mean test AUC results, DNN ranks 6th, 4th, and 3rd when predicting 5-year, 10-year, and 15-year BCM respectively, out of 10 machine learning methods. The top performing methods in predicting 5-year BCM are XGB(1^st), RF(2^nd), and KNN(3^rd). For predicting 10-year BCM the top performers are XGB (1^st), RF(2^nd), and NB(3^rd) . Finally, for 15-year BCM the top performers are SVM (1^st), LR and LASSO (tied for 2^nd), and DNN (3^rd). The ensemble methods RF and XGB outperform other methods when data are less balanced, while SVM, LR, LASSO, and DNN outperform other methods when data are more balanced. Our statistical testing results show that at a significance level of 0.05 DNN overall performs no worse than other machine learning methods when predicting 5-year, 10-year, and 15-year BCM. Conclusions Our results show that deep learning with grid search overall performs at least as well as other machine learning methods when using non-image clinical data. It is interesting to note that some of the other machine learning methods such as XGB, RF, and SVM are very strong competitors of DNN when incorporating grid search. It is also worth noting that the computation time required to do grid search with DNN is way more than that required to do grid search with the other 9 machine learning methods.

Reference evapotranspiration (ETo) is a key agrometeorological index for rational irrigation management. The standard method for ETo estimation, proposed by FAO, is based on a complicated Penman-Monteith equation, requires great number of meteorological inputs thus making it difficult for practical use by farmers. To the moment, there are many alternative simplified approaches for ETo estimation, most of them are directed to cutting the number of required meteorological inputs for calculation. Among them, special attention should be paid to various temperature-based methods of ETo assessment. One of the temperature-based models for ETo computation was realized in free mobile app ETo Calculator (Ukraine). The app gives Ukrainian farmers an opportunity to assess ETo values on daily or monthly scale using mean air temperature as the only input. The goal of the study was to test the app accuracy comparing to FAO-based calculations in five key regions of Ukraine, each of which representing a particular climatic zone of the country. It was established that the app provides relatively good accuracy of ETo estimation even in raw (not adjusted to windspeed and relative air humidity) run; the results of statistical comparison with the FAO-calculated values are: R2 within 0.82-0.87, RMSE within 0.74-0.81 mm, MAE within 0.60-0.70, MAPE within 18.07-25.50% depending on the region. ETo Calculator (Ukraine) is a good alternative for complicated Penman-Monteith method and could be recommended for Ukrainian farmers to be used for irrigation management.

The previous two parts of the paper (correspondingly, https://philpapers.org/rec/PENFLT-2 and https://philpapers.org/rec/PENFLT-3) demonstrate that the interpretation of Fermat’s last theorem (FLT) in Hilbert arithmetic meant both in a narrow sense and in a wide sense can suggest a proof by induction in Part I and by means of the Kochen - Specker theorem in Part II. The same interpretation can serve also for a proof FLT based on Gleason’s theorem and partly similar to that in Part II. The concept of (probabilistic) measure of a subspace of Hilbert space and especially its uniqueness can be unambiguously linked to that of partial algebra or incommensurability, or interpreted as a relation of the two dual branches of Hilbert arithmetic in a wide sense. The investigation of the last relation allows for FLT and Gleason’s theorem to be equated in a sense, as two dual counterparts, and the former to be inferred from the latter, as well as vice versa under an additional condition relevant to the Gödel incompleteness of arithmetic to set theory. The qubit Hilbert space itself in turn can be interpreted by the unity of FLT and Gleason’s theorem. The proof of such a fundamental result in number theory as FLT by means of Hilbert arithmetic in a wide sense can be generalized to an idea about “quantum number theory”. It is able to research mathematically the origin of Peano arithmetic from Hilbert arithmetic by mediation of the “nonstandard bijection” and its two dual branches inherently linking it to information theory. Then, infinitesimal analysis and its revolutionary application to physics can be also re-realized in that wider context, for example, as an exploration of the way for physical quantity of time (respectively, for time derivative in any temporal process considered in physics) to appear at all. Finally, the result admits a philosophical reflection of how any hierarchy arises or changes itself only thanks to its dual and idempotent counterpart.

Cells actively sense differences in topology, matrix elasticity and protein composition of the extracellular microenvironment and adapt their function and morphology. In this study, we focus on the cross-talk between matrix stiffness and protein coating density that regulate morphology and proliferation dynamics of single myocytes. For this, C2C12 myocytes were monitored on L-DOPA functionalized hydrogels of 22 different elasticity and fibronectin density compositions. Static images were recorded and statistically analyzed to determine morphological differences and to identify the optimized extracellular matrix (ECM). Using that information, selected ECMs were used to study the dynamics before and after cell proliferation by statistical comparison of distinct cell states. We observed a fibronectin density independent increase of the projected cell area until 12 kPa. Additionally, changes in the fibronectin density led to an area optimum at about 2.6 μg/cm, which was confirmed by an independent F-actin analysis, revealing a maximum actin filament to cell area ratio of 7.5 %. The proliferation evaluation showed an opposite correlation between cell spreading duration and speed to the matrix elasticity and protein density, which did not affect the cell cycle duration. In summary, we identified an optimized ECM composition, while independent matrix properties regulate distinct cell characteristics.

This paper presents an approach to the elastic analysis of beams subjected to Saint-Venant torsion using Green’s theorem and the finite difference method (FDM). The Saint-Venant torsion of beams, also called free torsion or unrestrained torsion, is characterized by the absence of axial stresses due to torsion; only shear stresses are developed. A solution to this torsion problem consists of finding a stress function that satisfies the governing equation and the boundary conditions. The FDM is an approximate method for solving problems described with differential equations; it does not involve solving differential equations, equations are formulated with values at selected nodes of the structure. In this paper, the beam’s cross-section was discretized using a two-dimensional grid and additional nodes were introduced on the boundaries. The introduction of additional nodes allowed us to apply the governing equations at boundary nodes and satisfy the boundary conditions. Beams with solid sections as well as multiply connected cross-sections were analyzed using this model; shear stresses and localized stresses at reentrant corners, torsion constant, and warping displacements were determined. Furthermore, beams with thin-walled closed sections, single-cell or multiple-cell, were analyzed using the Prandtl stress function whereby a linear distribution of the shear stresses over the thickness was considered; closed-form solutions for shear stresses and torsion constant were derived. The results obtained in this study showed good agreement with the exact results for rectangular cross-sections, and the accuracy was increased through a grid refinement. For thin-walled closed sections, the shear stresses obtained at the centerline using the closed-form solutions were in agreement with the values using Bredt’s analysis but the maximal values in the cross-section, which did not necessarily occur at the position with the smallest thickness, were higher; in addition, the results using the closed-form solutions were in good agreement with those using FDM.

On 11th March 2020, the World Health Organization declared COVID-19 as a pandemic. Vaccination programs have advanced greatly in the global health period, despite widespread anti-vaccination attitudes and misinformation. Vaccine hesitancy of COVID-19 vaccine is currently a major issue in Saudi Arabia. This cross-sectional study was carried out from June 25, 2021 to October 2021 in order to investigate the knowledge levels of acceptance and hesitancy of COVID-19 vaccine among Saudi’s nationals. The data was collected through a close-ended structured questionnaire from a total of 565 respondents. Overall, 78.41% respondents were female, 62.48% having university level education and 61.06% were unemployed. Majority of the participants 82.30% (n=465) think that Pfizer vaccine has the highest efficiency against COVID-19. Our study concludes that majority of the participants have satisfactory knowledge about COVID-19 vaccination. Concerns over vaccine components, effectiveness of vaccine and possible side effects are among the key causes for vaccine hesitancy.

Background: Handover is a critical process for ensuring quality and safety in healthcare. Considerable research suggests that poor handover results in significant morbidity, mortality, dissatisfaction, and excess financial costs. Despite this, little formal attention, education, and evaluation has been given to handover. There is also paucity of data on the opinions of practitioners on the safety of handover.Objectives: The aim of this study was to measure the perceived risk, degree of patient harm and the systems used to support handover, and to understand how this varied by care setting, type of clinical practice, location, or level of experience. Methods: An open, anonymous and confidential online questionnaire covering: (a) respondent characteristics; (b) peer-to-peer handover; (c) internal referrals; (d) discharges and transfers between organisations; and (e) leading and improving handover was conducted with healthcare practitioners and managers from various settings. Results: We gathered a total of 432 completed responses from 26 countries. The average reported performance of handover was rated as 3.9 out of 5.For each type of handover, 12 - 14% reported errors occurring more than weekly. Of those that knew the outcome of such errors, between 29% and 34% reported that they had witnessed moderate or severe harm. 12% and 17% of respondents believed that handover was high or very high risk (See table 4). These respondents were more likely to have witnessed moderate or severe harm, or to be more senior.A wide combination of handover systems was utilised by respondents. 28% - 32% relied exclusively on EPRs (with or without face-to-face contact). 21% used Office documents such as Word and Excel for peer-to-peer handover, and over 30% used hand-written or manual systems. Conclusions: This study suggests the need to do more — and go further — to improve communication and reduce risk during all types of handovers. Clinical leaders should find ways to train and support handover with effective systems, with less experienced staff being the primary focus. More research is needed to demonstrate the interventions that improve the safety of handover.

Indirect imaging methods involve at least two steps, namely optical recording, and computational reconstruction. The optical recording process uses an optical modulator that transforms the light from the object into a typical intensity distribution. This distribution is numerically processed to reconstruct the object’s image corresponding to different spatial and spectral dimensions. There have been numerous optical modulation functions and reconstruction methods developed in the past years for different applications. In most cases, a compatible pair of optical modulation function and reconstruction method gives optimal performance. A new reconstruction method termed non-linear reconstruction (NLR) was developed in 2017 to reconstruct the object image in the case of optical scattering modulators. During the years, it was revealed that the NLR could reconstruct an object’s image modulated by an axicons, bifocal lenses and even exotic spiral diffractive elements, which generate deterministic optical fields. Apparently, NLR seems to be a universal reconstruction method for indirect imaging. In this review, the performance of NLR has been investigated for many deterministic and stochastic optical fields. Simulation and experimental results for different cases are presented and discussed.

In an attempt to improve free-range beef cattle herds and explore the economic viability of utilizing Opuntia ficus-indica (spineless cactus) cladodes as supplementary feed, we investigated the impact of cactus diets on animal growth performance and carcass characteristics of Nguni cattle heifers. Four dietary treatments were randomly assigned to 32 heifers aged 24-months, weighing on average 172.2±27.1 kg, with each dietary treatment replicated to 8 individually penned heifers for 90 days. The dietary treatments were control diet (pasture-based energy + protein sources), 10% cactus diet, 20% cactus diet and commercial diet (crop-based energy and commercial protein source). The heifers fed commercial and control diets attained significantly (P < 0.05) higher dry matter intake, average daily gains, fat thickness, carcass conformation scores and lower feed conversion ratio than those fed cactus diets. However, the final body weight gains, slaughter and carcass weights, rib-eye muscle area and meat pH45 min and 24h were comparable (P > 0.05) between heifers fed cactus diets and those fed commercial and control diets. The 10 and 20% cactus diets had greater gross margins (P < 0.05) of R278.6 and R296.9, respectively than the other diets, due largely to reduced total variable costs. The comparability of carcass traits of heifers fed cactus diets and those fed non-cactus diets as well as higher economic returns from cactus inclusion warrants the use of cactus diets, particularly during drought when commercial feed prices rise.

BACKGROUND. Two sequelae of non-alcoholic steatohepatitis (NASH), ESLD and HCC, have become the leading causes for liver transplantation in the Western. The present study aims to approach the cellular metabolic disturbances involved in NASH progression that are associated with microbiota community changes. METHODS. Metabolic effects and microbiota community changes were explored in the murine with NASH progression by blocking the Na/K-ATPase/Src/reactive oxygen amplification loop using the synthetic targeting peptide pNaKtide. DNA from the terminal ileum microbiota habitat was obtained and amplified by PCR to develop DNA bacterial phylogenic sequence analysis of wild type and treated animals at 12, 24 and 48 weeks. Induced changes by pSrc normalization at 24 weeks were correlated with liver morphological changes, intestinal CD4+/CD8+ ratio, and liver macrophage CD14+ expression. Differences among groups were evaluated by ANOVA/t-test and Principal Component Analysis (PCA). RESULTS. Microbiota communities varied significantly at all time points (12, 24 and 48 weeks), with an increase of Verrucomicrobia and a decrease of Bacteroidetes and Firmicutes in the HFD group. Microbiota community changes regressed to their wild-type state at 24 weeks on treated animals, and those changes were associated with a decrease in liver inflammation and senescence, lower ileum CD4+/CD8+ T cells and higher liver CD14+ cells (p<0.05). Concomitantly, the metabolic disturbances in our diet-induced NASH model were normalized by NKA/Src signaling blockage and exercise with a paucity of apoptotic activity, mitigation of cell senescence, and regression of liver fibrosis (p<0.01). CONCLUSIONS. pSrc inhibition at caveolar α1-Na/K-ATPase rescinded NASH-related metabolic disturbances establishing resident physiological microbiota communities with concomitant paucity on apoptotic activity and regression of liver fibrosis; effects that were associated with both gut and liver T-lymphocyte responses.

Insect herbivores have a wide range of life cycles and feeding habits, making them extremely diverse. With their host plants, they form close relationships and suppress their defense mecha-nisms. Molecular elicitors are the key bio-elements in detection and recognition of attacking enemies in tissue consumption. Insect oral secretion, frass, and fluid of egg deposition contain bio-logical active molecules called herbivore-associated elicitors (HAEs) are recognized by pattern recognition receptors (PRRs). However, in insect herbivores, little is known about the molecular basis of signal transduction and regulation of plant resistance. Many plants distinguish insect feeding from wounding by HAEs presenting in their oral secretions (OS) and induce local and systemic responses against arthropod feeding. PRRs perceive HAEs in the oral secretion of cater-pillars in a species-specific manner to elicit exclusive defense responses. HAEs-PRRs interactions induce plant resistance by reprogramming plant metabolism and transcriptional machinery. Quantitative, timely, and coordinated plant response initiate early signalling events including Ca+2, reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs). We have discussed how early signalling cascades converge into the accumulation of phytohormones that regulate down-stream special metabolites against herbivores. In this review, we have drawn a hypothetical model of PPRs-HAEs mediated induced responses in plants and discussed how PRRs-HAEs interactions based on molecular mechanism that elicit short- and long-term induced defenses in plants. The identification of plant target insect herbivore PRRs-HAEs interactions will help to explore the fundamental molecular mechanisms of host manipulation and may generate prospects to develop novel pest resistance strategies.

Three-phase motors are commonly adopted in several industrial contexts and their failures can result in costly downtime causing undesired service outages; this way, motor diagnostics is an issue that assumes great importance. To prevent their failures and timely face the considered service outages, a non-invasive method to identify electrical and mechanical faults in three-phase asynchronous electric motors is proposed in the paper. In particular, a measurement strategy along with a machine learning algorithm based on Artificial Neural Network is exploited to properly classify failures. In particular, digitized current samples of each motor phase are first processed by means of FFT and PSD in order to estimate the associated spectrum. Suitable features (in terms of frequency and amplitude of the spectral components) are then singled out to either train or feed a neural network acting as a classifier. The method is preliminary validated on a set of 28 electric motors, and its performance is compared with common state-of-art machine learning techniques. The obtained results show that the proposed methodology is able to reach accuracy levels greater than 98\% in identifying anomalous conditions of three-phase asynchronous motors.

Artificial intelligence is dramatically transforming medical imaging. We assessed the levels of artificial intelligence use among radiology trainees and explored their perceived impact of artifi-cial intelligence on the radiology workflow and radiology profession, in correlation with the perceived ease of use and behavioral intention to use artificial intelligence. This cross-sectional study enrolled radiology trainees from Saudi Arabia, and an online 5-part-structured question-naire was disseminated via online networks to trainee in July 2021. We included 98 participants (51 male; age 27.59±2.02 years). Level of use was low; few used it in routine practice (7%). The impact of artificial intelligence on the radiology workflow was positively perceived in all radi-ology workflow steps (3.64–3.97 out of 5). A positive impact on the radiology profession was more frequently perceived for technical and performance aspects (81%–85%) compared with prestige and legal aspects (64%–71%). Perceived ease of use and behavioral intention to use arti-ficial intelligence was associated with the current professional activity, level of use artificial in-telligence use, and perceived impact on the profession as well as on radiology workflow (p<0.05). Levels of artificial intelligence use in radiology are very low. The perceived positive impact of ar-tificial intelligence on radiology workflow and profession is correlated with an increase in be-havioral intention to use artificial intelligence. Thus, increasing awareness about the favorable impact can improve the behavioral use.

Due to rising global warming and climate change, biodiversity protection has become a critical ecological concern. The rich biodiversity zones are under threat and are deteriorating, necessitating national, regional, and provincial efforts to safeguard these natural areas. The effective conservation of National Parks and Nature-protected Areas helps to improve biodiversity conservation, forest, and urban air quality. The continuous encroachment and abuse of these protected areas have degraded the ecosystem over time. While exploring the geophysical ecology and biodiversity conservation of these areas in West Africa, Kainji National Park was selected for this study because of its notable location, naturalness, rich habitat diversity, topographic uniqueness, and landmass. The conservation of national parks and nature-protected areas is a cornerstone of biodiversity conservation globally. This study is aimed at the target of United Nations Sustainable Development Goal 13, 2030- Climate Action, targeted at taking urgent action towards combating climate change and its impacts. The study captures both flora and fauna that are dominant in the study area. The 15 identified tree species were selected from over 30 species with 563,500,000 (an average of 3,700,000 in each sample frame) trees for every tree species/type with a total of 63% tree green canopy cover. The study areas divided into three zones were randomly sampled within a stratum of 25x25km frames divided into 150 sample frames for proper analyses using the i-Tree Eco v6.0.23. The following microclimatic data were captured and analyzed; photosynthetically active radiation, rain/precipitation, temperature, transpiration, evaporation, water intercepted by trees, avoided a runoff by trees, potential evaporation by trees, isoprene and monoterpene by trees. This study also further discusses the tree benefits of a green, low carbon, and sustainable environment within the context of biodiversity conservation considering carbon storage, carbon sequestration, hydrology effects, pollution removal, oxygen production, and volatile organic compounds (VOCs). There is a quick need for remotely-sensed information about the protected areas at regular intervals and government policies must be strict against illegal poaching, logging activities and other hazardous human impacts.

The molecular clusters ((HO)3Si-O-Si(OH)3, and (HO)3Al-O-Si(OH)3 ) representative of aluminosilicate mineral surface were employed to study the dissolution of aluminosilicate in acidic condition via density functional theory with the M06-2X+G(d,p) methodology. The surface termination sites (Si and Al) were both tetra-coordinated and the terminal oxygen was protonated in acidic condition. In the dissolution reaction, the calculated barrier height of the six-membered ring transition state complex containing two water molecules was predicted to be lower than that of four-membered ring transition state complex containing one water molecule. In addition, the calculated barrier heights for Al-terminated sites were predicted to be lower than those for the Si-terminated sites, suggesting that breaking the Al-O bond is easier than Si-O bond in the aluminosilicate mineral surface; the barrier heights of the surface termination sites with protonated terminal oxygen were lower than those without protonated terminal oxygen. With the fracture of Si-O and Al-O bonds, the Si and Al release from the aluminosilicate. These results confirm the experimental conclusions that the acidic condition facilitates the release of Si and Al from the aluminosilicate, and the concentration of Al leaching from aluminosilicate is higher than Si.

Institutional barriers can hinder effective access and utilisation of Newcastle disease vaccines among smallholder chicken farmers. Many studies have focused on formal institutional barriers with minimal focus on informal institutions - unwritten rules and regulations that govern access and utilisation of Newcastle vaccines. However, informal institutions are more profound and encultured in individuals’ daily activities. This study sought to investigate informal institutional barriers to access and utilisation of Newcastle disease vaccines among women smallholder chicken farmers in Makueni, Kenya. The cross-sectional qualitative study employed in-depth interviews, key informant interviews and focus group discussions as data collection methods. Study informants were conveniently and purposively sampled. Informal institutional barriers to access and utilisation included: fear of Newcastle disease vaccine as a new technology, use of herbal remedies, mistrust of community vaccinators, gender division of labour, ownership of household resources and beliefs that indigenous chickens do not need vaccines. The study concludes that women chicken farmers are constrained by unwritten rules, norms, regulations and gender roles that hinder their access to and utilisation of the Newcastle disease vaccines. The need to examine informal institutions to identify and eradicate barriers to access and utilisation of Newcastle disease vaccines by farmers is recommended.

Load variations in any power system result in losses escalation and voltage drops. With the sensible and optimal allocation of distributed generators (DGs), these problems could be considerably mitigated. It has been seen in the priorly existing methods that ideally allocation of DGs has been carried out during fixed loads and constant power requirements. However, in real scenarios the loads are always variable and allocation of DGs must be done in accordance to the variations of the connected load. Therefore, the current paper addressed the aforementioned problem by distinctive optimal allocation of DGs for each variability of 24hour load horizon. However, the single exclusive solution is considered among all allocations of 24 hours. The min-max regret concept has been utilized in order to deal with such methodology. Altogether, 24 scenarios are analyzed wherein each scenario corresponds to a specific hour of the respective day. The optimal allocation of DGs in terms of their optimal sizing and placement has been carried out by using three algorithms including battle royal optimization (BRO), accelerated particle swarm optimization (APSO) and genetic algorithm (GA). The multi-objective optimization problem is evaluated on the basis of minimum value criterion of the multi-objective index (MO). MO comprises of active and reactive power losses and voltage deviation. Hence, in order to find robustness of proposed technique, Conseil international des grands réseaux electriques (CIGRE’s) MV benchmark model incorporating 14 buses has been considerably used as a test network. In the end the results of three proposed algorithms have been compared.

Abstract: Background: Our goal was to evaluate whether wearing personal protective equipment (PPE) such as an N95, or a surgical mask during the (COVID-19) pandemic had really reduced the cases of influenza in the state of Wisconsin. Methods: Respiratory Virus Surveillance Reports from the Wisconsin Department of Health Services (DHS) and the Centers for Disease Control and Prevention (CDC) were used to compare the rates of Influenza during the seasons of 2018-2019 and 2020-2021. Results: The number of cases, hospitalizations, and mortality rates with Influenza had significantly decreased in the 2020-2021 season compared to the Influenza season of 2018-2019. Discussion: Reducing the burden of influenza illnesses, hospitalizations, and deaths on the health care system is imperative. Wearing masks should be addressed for the most vulnerable.

Zinc protection of galvanized steel is initially dissolved in alkaline solutions. However, passive layer is formed over time which protects the steel from corrosion. The behavior of galvanized steel exposed to strong alkaline solutions (pH values of 12.7) with a fixed concentration of sulfate ion of 0.04M is studied. Electrochemical measurement techniques such as corrosion potential, linear polarization resistance and electrochemical impedance spectroscopy are used. Synergistic effect of sulfate ion is also studied together with other anions such as chloride Cl- or bicarbonate ion HCO3- and with other cations such as calcium Ca2+, ammonium NH4+ and magnesium Mg2+. Presence of sulfate ions can depassivate the steel, leading to corrosion density of 0.3 µA/cm2 at the end of the test. The presence of other ions in the solution increases this effect. The increase in corrosion density caused by cations and anions responds to the following order (greater to lesser influence): NH4+&gt;Ca2+&gt;Mg2+ and HCO3- &gt;Cl- &gt;SO42-.

Cancer has emerged as a systemic disease which targets various organs thus challenging the overall physiology of the host. Recently, we have shown that hyperactive neutrophils infiltrate various organs of tumor bearing host and contribute significantly to gradual systemic deterioration. Therefore, taming neutrophils via potent immunomodulators could be an appropriate therapeutic approach in regulating systemic damage. Tinospora cordifolia (TC), an Ayurvedic panacea, is known for its immense medicinal values in traditional literature and recent reports have also documented its strong immunomodulatory potential. However, whether TC can regulate neutrophils to exert its therapeutic effectiveness has not been deciphered so far. To discern this, we utilized murine model of Dalton’s Lymphoma (DL) wherein, we have earlier reported heightened infiltration of neutrophils and their hyperactivation. Our findings showed that TC treatment significantly reduced neutrophil count in peripheral blood and their infiltration in vital organs of tumor bearing host. Further, it ameliorated neutrophil hyperactivation by down regulating the expression of its key cargoes including neutrophil elastase (NE), myeloperoxidase (MPO), MMP-8, MMP-9 and cathepsin G (CSTG) at early and mid stage of tumor growth. In addition, TC treatment prevented histopathological alterations and restored the normal serum enzyme levels at different stages of tumor growth. Importantly, TC treatment also showed significant reduction in tumor burden which was accompanied by a remarkable increase in survival of the tumor-bearing mice. We conclude that Tinospora cordifolia could limit systemic damage via regulating neutrophil infiltration and hyperactivation which can further lead to cancer control at both prophylactic and therapeutic level.

Providing healthcare workers with cost information about the medications they prescribe can influence their decisions, particularly when that information is provided at the very moment they are faced with a prescribing decision. The current study aimed to analyse the impact of nudges that presented cost information to prescribers through their organisation's electronic prescribing system. The nudges were co-created by the research team (composed of behavioural scientists) and the lead hospital pharmacist. One nudge provided simple cost information (percentage difference between two brands of Mesalazine – Asacol and Octasa). The second nudge provided the potential annual cost-saving that could result if the cheaper medication was selected across the organisation. While the statistical analyses revealed that these nudges were not effective, several administrative barriers were overcome, which may inform future research. For example, presenting aggregated cost information to the prescribers is possible even when the actual cost of medicine is confidential and can not be displaced. In addition, future research could reveal more behavioural factors that facilitate medication optimisation.

Background: This study aims to set out key clinical features of different Motoric Cognitive Risk (MCR) subtypes based on individual quantitative measures of cognitive impairment and to compare their predictive power on survival over an 8-year observation time. Methods: We analyzed data from a population-based study of 1138 subjects aged 65 years and older in south Italy. These individuals were targeted and allocated to subtypes of the MCR phenotype according to the slowness criterion plus one other different cognitive domain for each characterized phenotype. Clinical evaluation and laboratory assays, along with a comprehensive battery of neuropsychological and physical tests, completed the sample investigation. Results: MCR prevalence was found to be 9.8% (N=112), 3.6% (N=41), 3.4% (N=39), and 1.8% (N=21) for the MCR, MCR-GlobalFunction, MCR-StructuredSCC, and MCR-SCC&amp;GlobalFunction, respectively. Univariate Cox survival analysis showed an association only of the MCR-GlobalFunction subtype with a significant, 1.5-fold increased risk of overall death as compared to the other counterparts (HR 2.53, 95%CI 1.28 to 4.99, P-value&lt;0.01) over an 8-year observation period, even after major adjustment (HR 2.02, 95%CI 1.02 to 4.02). Conclusions: MCR phenotypes assigned to the MMSE cognitive domain are more likely to have an increased risk of overall mortality, 1.5-fold higher than counterparts, over 8-year observation.

Rotary tillage is a main management tillage practices and widely applied in the North China Plain. However, the long term rotary tillage (depth of 20 cm) results in soil compaction and plow pan formation, which reduces water use efficiency and nutrient uptake, and then impedes the yield increase. In this study, a 3-year field experiment was conducted to investigate the influence of different depths of tillage on soil bulk density, field capacity, water use, photosynthetic rate, nutrients and maize yields in the North China Plain. Three depths of tillage (D20, depth of 20 cm; D25, depth of 25 cm; D30, depth of 30 cm) were assessed. D25 and D30 significantly reduced soil bulk density and improved field capacity in 10-20 and 20-30 cm soil layer, compared to D20. Soil water consumption for D25 was significantly higher 10.12% and 6.61% than that for D20 and D30, respectively. Photosynthetic rate for D25 significantly improved than that for D20 and D30. Total nitrogen in 0-20cm soil layer decreased with the depths of tillage. The maize yields for D25 significantly increased by 20.92% and 21.56% compared to that for D20 and D30, respectively. Structural equation models showed that the total effects of tillage, total nitrogen, photosynthesis and soil water consumption on yields were 0.019, -0.628, 0.121, and 0.895 (path coefficients λ), respectively. The results demonstrated that D25 could improve maize yields, water use efficiency, photosynthetic rate by improving soil water consumption. Depth of 25 cm is optimal tillage practice for the maize production in the North China Plain.

Several recent epidemiological studies attempted to identify risk factors for Alzheimer's disease. Age, family history, genetic factors (APOE genotype, Down syndrome), physical activity, and a low level of schooling are significant risk factors. In this review, we summarize the known psychosocial risk factors for the development of Alzheimer's disease in Down syndrome patients and their association with neuroanatomical changes in the brains of people with Down syndrome. We completed a comprehensive review of the literature on PubMed, Google Scholar, and Web of Science about psychosocial risk factors for Alzheimer's disease, for Alzheimer's disease in Down syndrome, and Alzheimer's disease in Down syndrome and their association with neuroanatomical changes in the brains of people with Down syndrome. Alzheimer's disease causes early pathological changes in Down syndrome patients, especially in the hippocampus and corpus callosum. The field needs more data about the neuroanatomical changes during childhood, how they change with increasing age, and the presence or absence of psychosocial risk factors. Further neuroimaging and psychosocial assessment-focused research is needed to understand the mechanisms leading to Alzheimer's disease at an early age and create more sensitive and relevant clinical, memory, and reasoning assessments for people with Down syndrome.

White-rot fungi (WRF) have specific enzymes to degrade lignocellulosic and phenolic compounds. Therefore, their direct application could be an alternative to biodegrade complex lignocellulosic biomass such as olive mill solid waste (OMSW). The aim of this study was to evaluate the capacity of A. discolor and S. hirsutum to grow in OMSW as the sole substrate under static conditions and evaluate the phenolic removal compounds and lignin degradation. The lignolytic enzyme activity was determined, as was the phenolic compound removal. At the same time, lignin degradation and structural changes were evaluated by confocal laser scanning microscopy (CLSM) and scanning electron microscope (SEM), respectively. Both strains were able to grow using OMSW as the sole substrate without adding other nutrients, oxygen and/or agitation. The higher ligninolytic enzyme activity was found at day 8, and the highest phenolic removal (more than 80% with both strains) was reached after 24 days of incubation. The CLSM analysis confirmed lignin degradation through the drop in lignin fluorescence from 3967 for untreated OMSW to 235 and 221 RFU after 24 days of treatment by A. discolor and S. hirsutum respectively. The results indicate that both WRF could be suitable candidates to design an in-situ pretreatment step of OMSW, as long as in future research the WRFs have the same performance in non-sterile conditions.

Modern agriculture demands for comprehensive information about the plant itself. Conventional chemistry-based analytical methods - due to their low throughput and high associated cost - are no longer capable of providing these data. In recent years, remote reflectance-based characterization has developed as one of the most promising solutions for rapid assessments for plant attributes. However, in many cases, expensive equipment is required because accurate quantifications need assessment of the full reflectance spectrum. We examined the versatility of visible colour sensors as reflectance measuring devices for biological / biochemical quantifications on sweet basil (Ocimum basilicum). Our results indicate for the wide potential of spectral colour sensors for quantitative determination of leaf phenolic compounds, flavonoids in particular, and non-invasive plant phenotyping in agricultural applications by low-cost sensors.

In this paper, the classical least square (CLS) method with molecular absorption spectrophotometric measurement was used to determine simultaneously of paracetamol (PAR), ibuprofen (IBU), and caffeine (CAF) in tablets. The absorbance spectra of the standard solutions and samples were measured over a wavelength from 220 to 300 nm with a 0.5 nm step. The concentration of PAR, IBU and CAF in the sample solutions were calculated by using a program called CLS-Excel written in Microsoft Excel 2016 and Visual Basic for Applications (VBA). The method and CLS-Excel program were tested on mixed standard laboratory samples with different PAR, IBU, and CAF concentration ratios, and they showed small errors and satisfying repeatability. An analytical procedure for tablets containing PAR, IBU, and CAF was developed. The reliability of the procedure was proved via the recovery and repeatability of the analysis results with an actual tablet sample and comparing the mean contents of active substances in the tablets obtained from the analytical procedure with the from the HPLC method. The procedure is simple with a reduced cost compared with the HPLC standard method.

Anticipating future successional forest trends in the face of ongoing global change is an essential conservation target. Mountain forests are especially sensitive to environmental shifts, and their past responses to climatic and anthropogenic (external) drivers may provide a basis for improving predictions of future developments. This paper uses independent high-resolution palynological and paleoclimatic reconstructions to statistically analyze the long-term effects of external drivers on regional forest succession in the central Iberian Pyrenees during the last 500 years. The dominant taxa of these forests (Quercus, Betula, Pinus) showed significant relationships with summer temperature, summer drought and autumn precipitation. Immediate and delayed (by two or more decades) responses of these trees to climatic drivers were identified. Regional succession showed a closed path, starting at the end points around the attraction domain of pine-dominated forests. This trajectory was determined by a trend toward anthropogenic forest clearing (16th to 18th centuries) and a reverse trend of natural forest recovery (18th to 20th centuries). Forest clearing was due to burning, facilitated by drought, and was followed by the expansion of cropping and grazing lands. Forest recovery was fostered by reduced human pressure and rising temperatures. The statistical approach used in this work has unraveled ecological relationships that remained unnoticed in previous works and would be important for predicting future successional trends under changing climates. The reported response lags of individual taxa to climatic drivers may complicate the establishment of reliable ecological relationships and should be addressed in future studies.

Undisturbed ground temperature (UGT), thermal conductivity (TC) and heat capacity (HC) are essential parameters for the design of borehole heat exchanger (BHE) and borehole thermal energy storage systems. However, field methods to assess the thermal state and properties of the sub-surface are costly and time consuming. Moreover, HC is often not evaluated but arbitrarily selected from literature considering the geological materials intercepted by boreholes. Therefore, this work aims at proposing a field heat tracing method to infer the thermal diffusivity (TD) and HC with assumption of natural transient heat conduction in the subsurface. Empirical equations were developed to reproduce a UGT profile measured along a BHE. Experimental coefficients are found with a non-linear least square solver optimization and used to calculate the damping depth and TD. Subsequently, the TD is used to evaluate HC considering TC obtained from a thermal response test (TRT). Results from this proposed heat tracing method were verified and validated against a set of TRT results and oscillatory TRT analysis using a field dual probe concept to infer HC. The example here described highlights the advantages and novelty of this fast and simple field method relying only on a single UGT profile measured before a TRT.

Smart Internet of Vehicles (IoVs) combined with Artificial Intelligence (AI) will contribute to vehicle decision-making in the Intelligent Transportation System (ITS). Multi-Vehicle Pursuit games (MVP), a multi-vehicle cooperative ability to capture mobile targets, is becoming a hot research topic gradually. Although there are some achievements in the field of MVP in the open space environment, the urban area brings complicated road structures and restricted moving spaces as challenges to the resolution of MVP games. We define an Observation-constrained MVP (OMVP) problem in this paper and propose a Transformer-based Time and Team Reinforcement Learning scheme (T3OMVP) to address the problem. First, a new multi-vehicle pursuit model is constructed based on decentralized partially observed Markov decision processes (Dec-POMDP) to instantiate this problem. Second, by introducing and modifying the transformer-based observation sequence, QMIX is redefined to adapt to the complicated road structure, restricted moving spaces and constrained observations, so as to control vehicles to pursue the target combining the vehicle’s observations. Third, a multi-intersection urban environment is built to verify the proposed scheme. Extensive experimental results demonstrate that the proposed T3OMVP scheme achieves significant improvements relative to state-of-the-art QMIX approaches by 9.66%~106.25%. Code is available at https://github.com/pipihaiziguai/T3OMVP.

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to poor overall survival of patients. In colorectal cancer (CRC), hyper-activation of Wnt/β-catenin signaling by mutation of both Adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that the CPD0857 inactivates Wnt/β-catenin signaling by promoting ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing apoptosis of CRC lines. CPD0857 also decreased growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/β-catenin-Ras MAPK-PI3K/AKT signaling in CRCs.

Since the Paris Agreement in 2016, the goals of limiting climate change and moving toward climate resilience stand. With a share of about \SI{80}{\percent} of global \ce{CO2} emissions, the energy sector is an essential driver for these goals. A shift to low-carbon energy production and a decentralized system for more efficient energy transmission distribution is necessary. In this paper, we present our work on Modeling of Power Exchanges, Algorithms for \ac{LEM}, Competitiveness of \ac{CHP} and Energy Feedback Devices. The study was conducted considering technical, economic, social and regulatory framework. For easy integration into energy simulations or a \ac{DEMS}, a model for power exchanges was created that allows flexible input or deterministic price patterns. The algorithm handles the clearing of an \ac{LEM} by a district aggregator using limit orders with the goal of increasing the share of locally consumed electricity using economic incentives. An investigation was conducted into the operation of flexible \acp{CHP} in low-carbon power systems to balance the volatility of renewable energy. An energy signal light was developed as an energy feedback device, which is integrated into the \ac{DEMS} in a living lab and allows individual configuration. In summary, the results presented should be compared with those of other research approaches in the future and require qualitative and quantitative evaluation.

One of the earliest hallmarks of plant immune response is production of reactive oxygen spe-cies (ROS) in different subcellular compartments, which regulate plant immunity. A suitable equilibrium, which is crucial to prevent ROS over-accumulation leading to oxidative stress, is maintained by salicylic acid (SA), a chief regulator of ROS. However, ROS are not only acting downstream of SA signaling, but were also proposed to be a central component of a self-amplifying loop that regulates SA signaling as well as the interaction balance between dif-ferent phytohormones. The exact role of this crosstalk, the position where SA interferes with ROS signaling and ROS interferes with SA signaling and the outcome of this regulation depend on the origin of ROS but also on the pathosystem. The precise spatiotemporal regulation of or-ganelle specific ROS and SA levels determine the effectiveness of pathogen arrest and is there-fore crucial for a successful immune response. However, the regulatory interplay behind still remain poorly understood, as up till now, the role of organelle specific ROS and SA in HR-conferred resistance has mostly been studied by altering the level of a single component. In order to address these aspects, a sophisticated combination of research methods for monitoring the spatiotemporal dynamics of key players and transcriptional activity in plants is needed, and will most probably consist of biosensors and precision transcriptomics.

Background: A growing number of clinical practice guidelines (CPGs) with regards to non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistency of recommendations, it remains uncertain how best to design and implement such non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: Clinical practice guidelines which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using the Appraisal of Guidelines for REsearch and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions that were recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: Fourteen CPGs were identified and analysed. Of the 14 CPGs appraised, only five were rated as high quality. The domain with the highest standardised percentage was “scope and purpose” (84.61%), while the “applicability” domain had the lowest standardised percentage (51.04%). Five guidelines were assessed as “recommended”, seven were rated as “recommended with modifications”, and the remaining two were considered “not recommended”. Regarding the content analysis, physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage, and acupressure were the common self-managed non-pharmacological interventions recommended by the 14 CPGs. Physical activity/exercise was the only self-managed non-pharmacological intervention that was mostly recommended for psychological and physical symptom management by the included CPGs. However, there were significant disparities in terms of level of evidence and grade of recommendation in the included CPGs. Conclusion: The recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs in order to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

Genomics has put prokaryotic rank-based taxonomy on a solid phylogenetic foundation. However, most taxonomic ranks were set long before the advent of DNA sequencing and genomics. In this concept paper, we thus ask the simple yet profound question: Should prokaryotic classification schemes besides the current phylum-to-species ranks be explored, developed, and incorporated into scientific discourse? Could such alternative schemes provide better solutions to the basic need of science and society for which taxonomy was developed, namely, precise and meaningful identification? A neutral genome-similarity based framework is then described that could allow alternative classification schemes to be explored, compared, and translated into each other without having to choose only one as the gold standard. Classification schemes could thus continue to evolve and be selected according to their benefits and based on how well they fulfill the need for prokaryotic identification.

The main regulatory factors during the adaptation of cancer cells to hypoxic stress are the hypoxia-inducible factors (HIFs), which are being increasingly recognized as an interesting and challenging target for the design of new chemotherapeutic molecules. HIF2A was found to have an large internal hydrophilic cavity within its PAS-B domain, unique to this sub-unit and is suggested to be a possible ligand-binding site. Regulation of HIF2A by cellular molecules is still greatly unknown. In This paper we have employed in-silico techniques, such as molecular docking and dynamic simulation, to design new direct inhibitors against HIF-2A subunit via targeting one of its critical domains and the final top screened molecules have been tested on hypoxic cancer cells for further validation of their inhibitory potential. we targeted the hydrophilic cavity inside the PAS-B domain of the HIF2A to identify novel molecules with a high binding capacity. Virtual Screening methodology was used for molecular docking of NSC library against the target domain inside the HIF2A PAS-B domain with the top 5% compounds with significant MolDock and Re-rank scores were selected for further analysis. The NSC 106416, NSC 217021, NSC 217026, and NSC 215639 compounds were selected based on their docking scores. NSC 215639 had the minimum polar solvation energy and also had a relative strong binding energy. NSC 217026 had the strongest binding energy among other compounds.

Background: The course of obesity and type 2 diabetes (T2D) development is highly dependent on adipose tissue (AT) angiogenesis. Moreover, angiogenic microRNAs (miRNAs) play pivotal role in AT functionality. The aim of this study was to analyze the relationship of the human AT miR-221-3p/222-3p cluster and their regulatory network with obesity and T2D. Methods: miR-221-3p/222-3p and their target genes (TG) expression levels were measured in visceral and subcutaneous ATs from patients classified according to their BMI and to their glycemic status with a high degree of insulin resistance (IR) and T2D. In silico analyses of miR-221-3p/222-3p and their TGs were performed to identify relevant signaling pathways. Results: A multivariate analysis, including the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, showed significant differences considering the variables; tissue depot, obesity, IR and T2D altogether as independent variables. In addition, miRNAs and their TGs were differentially expressed according to obesity degree, glycemic status, and AT depot type. Our in silico analysis showed that miR-221-3p/222-3p cluster TGs are mostly involved in angiogenesis, WNT signaling pathway and apoptosis. Conclusion: These findings suggest that the miR-221-3p/222-3p cluster and their related regulatory networks could represent tangible targets for the management of obesity and associated metabolic disorders

Cholera is a severe diarrheal disease caused by Vibrio cholerae, a natural inhabitant of brackish water. Effective control of cholera outbreaks depends on prompt detection of the pathogen from clinical specimens and tracking its source in the environment. Although the epidemiology of chol-era is well studied, rapid detection of V. cholerae remains a challenge, and data on its abundance in environmental sources are limited. Here, we describe a sensitive molecular quantification as-say by qPCR, which can be used on-site in low resource settings directly on water without the need for DNA extraction. This newly optimized method exhibited 100% specificity for total V. cholerae as well as V. cholerae O1 and allowed detection of as few as three target genome copies per reaction. The limit of detection is as low as 5 × 10E3 genome copies/L of water after concentrat-ing biomass from the sample. The ability to perform qPCR directly on water samples, portable features of the equipment, stability of the reagents at 4°C and user-friendly online software facili-tate fast quantitative analysis of V. cholerae. These characteristics make this assay extremely use-ful for field research in resource-poor settings and could support continuous monitoring in cholera endemic areas.

A two phase survey of epilepsy was conducted in selected villages in Mundri West and East Counties (26 June−8 July, 2021), an onchocerciasis-endemic area in Western Equatoria State in South Sudan. In the first phase, households were visited by a trained research team to identify persons suspected to have epilepsy. In the second phase, persons suspected to have epilepsy were interviewed and examined by a clinician to confirm the diagnosis. A total of 364 households agreed to participate in the survey, amounting to 2,588 individuals. The epilepsy screening questionnaire identified 91 (3.5%) persons suspected to have epilepsy, of whom in 86 (94.5%) the diagnosis of epilepsy was confirmed by a clinician. The overall prevalence of confirmed epilepsy was 3.3% (95% CI: 2.7-4.1%), and of nodding syndrome 0.9% (95% CI: 0.6-1.4%). In 61 (16.8%) households there was at least one person with epilepsy. Only 1,212 (46.9%) of 2,583 people took ivermectin during the last distribution round in 2021. The annual epilepsy incidence was 77.3/100.000 (95% CI: 9.4-278.9/100,000) and the annual epilepsy mortality 251.2/100,000 (95% CI: 133.8-428.7/100,000). In conclusion, a high prevalence and incidence of epilepsy was observed in villages in Mundri. Urgent action is needed to prevent children from developing onchocerciasis-associated epilepsy by strengthening the local onchocerciasis elimination programme.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic still persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) increase of Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with increase of RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment of Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.

: This article was not intended to be a complete report of a standard clinical trial. It is a report of the outcomes of preliminary data for validation of the CMECD procedure (Coletti Method of EMG ChemoDenervation) protocol for the treatment of chronic pain resulting from chronic muscle spasm. Methods are here detailed on how to approach the patient with chronic pain, identify the presence of chronic muscle spasm, undertake the treatment protocol and how to perform the follow up process to confirm that chronic pain secondary to chronic muscle spasm was the accurate diagnosis. Furthermore, this article presents the results of a cohort of more than 90 patients treated by the CMECD procedure regarding location and duration of prior pain, prior treatment strategies, degree of success in resolving pain and duration of relief. Outcome data consisting of patient and staff reporting of specific situations in which the chronic pain treatment was successful has been included to help establish the “believability” of outcome successes and to elucidate the potential life altering effects of successful treatment of chronic pain secondary to chronic muscle spasm. This article will hopefully increase the interest in this treatment protocol and increase the chance that a classical international clinical trial will be undertaken.

Objective tools to track medication adherence are lacking. A tool to monitor pill intake that can be implemented in mHealth apps without the need for additional devices was developed. We propose a pill intake detection tool that uses digital image processing to analyze images of a blister to detect the presence of pills. The tool uses the circular Hough transform as a feature extraction technique and is therefore primarily useful for the detection of pills with a round shape. This pill detection tool is composed of two steps. First, the registration of a full blister and storing of reference values in a local database. Second, the detection and classification of taken and remaining pills in similar blisters, to determine the actual number of untaken pills. In the registration of round pills in full blisters, 100% of pills in gray blisters or blisters with a transparent cover were successfully detected. In counting of untaken pills in partially opened blisters, 95.2% of remaining and 95.1% of taken pills were detected in gray blisters, while 88.2% of remaining and 80.8% of taken pills were detected in blisters with a transparent cover. The proposed tool provides promising results for the detection of round pills. However, the classification of taken and remaining pills need to be further improved, in particular for the detection of pills with non-oval shapes.

Improving access to sexual health services is critical in light of rising sexually transmitted infections (STIs). We evaluated a Hub and Spoke model for improving access to sexual health services in three general practices in Victoria, Australia. The primary outcome was the impact on HIV and STI (chlamydia, gonorrhoea, syphilis) testing. Segmented linear regression analysis was conducted to examine the trends in the total HIV/STI tests before (from January 2019 to June 2020) and post-implementation (from July 2020 to July 2021). We evaluated the feasibility and acceptability of integrating this model into the general practices using semi-structured individual interviews. There was a statistically significant rise in testing for HIV and STIs in all general practices: post-implementation, there was an increase of an average of 11.2 chlamydia tests per month (p=0.026), 10.5 gonorrhoea tests per month (p=0.001), 4.3 syphilis tests per month (p=0.010), and 5.6 HIV tests per month (p=0.010). Participants reported increases in knowledge level and confidence in offering STI testing and managing more variety of sexual health cases. This study demonstrated the feasibility of implementing a hub and spoke model to enable GPs to deliver sexual health care with support from a sexual health specialist service.

The purpose of this work is to study quasi-stationary wave structure in the mid-latitude stratosphere and mesosphere (40–50°N) and its role in the formation of the annual ozone cycle. Geopotential height and ozone from Aura MLS data are used and winter climatology for January–February 2011–2020 is considered. More closely examined is the 10-degree longitude segment centered on Longfengshan Brewer station, China, and located in the region of the Aleutian Low influence associated with the quasi-stationary zonal maximum of total ozone. Annual and semi-annual oscillations in ozone were compared using units of ozone volume mixing ratio and concentration, as well as changes in ozone peak altitude and in time series of ozone at individual pressure levels between 316 hPa (9 km) and 0.001 hPa (96 km). The ozone maximum in the vertical profile is higher in volume mixing ratio (VMR) values than in concentration by about 15 km (5 km) in the stratosphere (mesosphere), in consistency with some previous studies. We found that the properties of the annual cycle are better resolved in the altitude range of the main ozone maximum: middle–upper stratosphere in VMR and lower stratosphere in concentration. Both approaches reveal SAO/AO-related changes in the of ozone peak altitudes in a range of 4–6 km during the year. In the lower-stratospheric ozone of the Longfengshan domain, an earlier development of the annual cycle takes place with a maximum in February and a minimum in August compared to spring and autumn, respectively, in zonal means. This is presumably due to the higher rate of dynamical ozone accumulation in the region of the quasi-stationary zonal ozone maximum. The “no-annual-cycle” transition layers are found in the stratosphere and mesosphere. These layers with undisturbed ozone volume mixing ratio throughout the year are of interest for more detailed future study.

Tobacco Free Nicotine (TFN) Electronic Nicotine Delivery Systems (ENDS) are yet to be classified as tobacco products; consequently, there is ambiguity over whether Food and Drug Administration (FDA) regulatory authority can be extended to include TFN e-cigarettes. In recent years, a more significant number of e-cigarette companies have been manufacturing TFN-containing e-cigarettes and e-liquids to circumvent FDA regulations. While studies have shown that aerosols generated from tobacco-derived nicotine-containing e-cigarettes contain significant Reactive Oxygen Species (ROS) levels, no comparison studies have been conducted using TFN e-cigarettes. This study uses a single puff aerosol generator to aerosolize TFN and tobacco-derived nicotine-containing vape-products and subsequently involves semi-quantifying ROS generated by these vape products in H2O2 equivalents. We found that the differences between ROS levels generated from TFN and tobacco-derived nicotine-containing vape products vary by flavor. TFN tobacco flavors and fruit flavors are more toxic in terms of ROS generation than menthol/ice and drink/beverage flavored products using TFN. The type of salt nicotine used in vape products, TFN or tobacco-derived nicotine, impacts the level of ROS generated from flavored vape products. Thus, a better understanding of the type of salt nicotine used in e-cigarettes (tobacco-derived or synthetic), has modulating effect on lung oxidative stress.

Abstract—Low-frequency Fahræus–Lindqvist-driven (not blood pressure-driven) oscillations in the small vessels are crucial because oscillations in small vessels support nutrient supply. Understanding of this is critical in type 2 diabetes mellitus (T2DM) to develop therapeutic measures to prevent Alzheimer's Disease Related Dementias: vascular factors contribute to cerebrovascular disease as well as mild cognitive impairment and dementia, which are predicted to affect 152 million people by 2050 (Alzheimer's Disease International London, UK, 2019). In this clinical study, we performed functional near-infrared spectroscopy (fNIRS) of the forehead to investigate the effect of the Mini-Cog with three-item recall test on the prefrontal cortex (PFC) activation and the relative oscillatory power in the 0.01–0.02-Hz (Fahræus–Lindqvist effect) and 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency bands in elderly (60 years and older) T2DM and age-matched controls. We found a significant (p<0.01) difference in the PFC activation between elderly subjects with T2DM and age-matched elderly controls. Moreover, power spectral density (PSD) analysis revealed a significantly lower relative power in 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency band in elderly subjects with T2DM during the Mini-Cog three-item recall test. Furthermore, a drop in the oscillatory power in the 0.01–0.02-Hz frequency band during Mini-Cog three-item recall test was found more pronounced in the elderly subjects with T2DM. Therefore, our study highlighted portable brain imaging to capture cerebrovascular reactivity to cognitive load that may provide a biomarker of cerebrovascular dysfunction in T2DM.Clinical Relevance— Our study establishes forehead portable brain imaging for monitoring cerebrovascular function in T2DM under cognitive load.

Amyotrophic lateral sclerosis (ALS) is also called "motor neuron disease”. In this review, we propose that ALS is not just a neuromotor disorder, but begins as a disorder of P53-modulated skeletal muscle metabolism, leading to failures at the energy state of the cells, incorrect redox states, motor denervation, and a loss of muscle fibers. Motoneurons die as a consequence of the lack of muscular feedback, and the oligomeric TDP43 aggregates progressively and relentlessly lead to mistakes in peripheral immune self-tolerance sustained over time. An effective treatment has not been found for this devastating pathology, as for 152 years the target has not been accurately defined. Scientists and doctors should consider new knowledge regarding ALS and consider immunomodulatory therapies that, based on genetic analysis and symptoms, can be combined with compounds that regulate metabolism and promote the elimination of useless organelles and cells. What if ALS could be cured as a result of seeing motor neuron disease differently? This review aims to develop that goal and change the paradigm of our understanding of ALS.

The direct radiative effects of atmospheric aerosols are essential for climate, as well as for other societal areas, like the energy sector. The goal of the present study is to exploit the newly devel-oped ModIs Dust AeroSol (MIDAS) dataset for quantifying the direct effects on the downwelling surface solar irradiance (DSSI), induced by the total and dust aerosols amount, under clear-sky conditions and the associated impacts on solar energy for the broader Mediterranean basin, over the period 2003 – 2017. Aerosol optical depth (AOD) and dust optical depth (DOD) derived by the MIDAS dataset, along with additional aerosol and dust optical properties and atmospheric variables were used as inputs to radiative transfer modeling to simulate DSSI components. A 15-year climatology of AOD, DOD and of clear-sky Global Horizontal Irradiation (GHI) and Direct Normal Irradiation (DNI) was derived. The spatial and temporal variability of the aerosol and dust effects on the different DSSI components was assessed. Aerosol attenuation of annual GHI and DNI range from 1-13% and 5-47%, respectively. Significant attenuation by dust 2-10% and 9-37% was found over North Africa and the Middle East, contributing to 45-90% of the total aero-sol effects. The mean GHI and DNI attenuation during extreme dust episodes reached values up to 12% and 44%, respectively, for different areas. After 2008 a decline of aerosol effects on DSSI was found, attributed mainly to the dust component. Sensitivity analysis using different AOD/DOD inputs from Copernicus Atmosphere Monitoring Service (CAMS) reanalysis dataset, revealed CAMS underestimation of aerosol and dust radiative effects compared to MIDAS, due to slight AOD and stronger DOD underestimation, respectively.

Background: Perinatal anxiety and related disorders are common (20%), distressing and impairing. Fear of childbirth (FoB) is a common type of perinatal anxiety associated with negative mental health, obstetrical, childbirth and child outcomes. Screening can facilitate treatment access for those most in need. Objectives: The purpose of this research was to evaluate the accuracy of the Childbirth Fear Questionnaire (CFQ) and the Wijma Delivery Expectations Questionnaire (W-DEQ) of FoB as screening tools for specific phobia, FoB. Methods: A total of 659 English-speaking pregnant women living in Canada and over the age of 18 were recruited to the study. Participants completed an online survey of demographic, current pregnancy, and reproductive history information, as well as the CFQ and the W-DEQ, and a telephone interview to assess specific phobia FoB. Results: Symptoms meeting full and subclinical diagnostic criteria for specific phobia, FoB were reported by 3.3% and 7.1% of participants, respectively. The W-DEQ met or exceeded the criteria for a “good enough” screening tool across several analyses, whereas the CFQ only met these criteria in one analysis, and came close in three others. Conclusions: The W-DEQ demonstrated high performance as a screening tool for specific phobia, FoB, with accuracy superior to that of the CFQ. Additional research, to ensure the stability of these findings, is needed.

The Seven Country study showed that traditional Japanese diet and Mediterranean diets are protective against cardiovascular diseases (CVDs). Japanese diet is considered the healthiest because it provides highest longevity and health to Japanese. DASH diet and Mediterranean style diets are also considered the healthy diets, although, it is possible that Indo-Mediterranean style diet may provide better protective effects among patients with CVDs, compared to other diets. The concept of Indo-Mediterranean type of diets was developed, after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France; The Lyon Heart Study. These workers found that eating alpha-linolenic acid rich Mediterranean style diet can cause significant decline in CVDs and all-cause mortality. Later on in 2018, PREDIMED Study from Spain also reported that a modified Mediterranean style diet can cause significant decline in CVDs, type 2 diabetes mellitus (T2DM) and cancer. The Indo-Mediterranean diet may be superior to DASH diet and Mediterranean diet because it contains millets, porridge, beans and spices; turmeric, cumin, fenugreek and coriander which may have better anti-inflammatory and cardio-protective effects. These foods are rich sources of nutrients; flavonoids, calcium and iron as well as proteins which are useful in the prevention of under as well as over-nutrition and related diseases. It is known that DASH diet and Mediterranean style diets have similar influence on CVDs. However, Indo-Mediterranean style diet, may be as good as Japanese diet, due to improved food diversity and high content of antioxidants in the diets.

This paper directly addresses a long-standing issue that affects the development of many complex distributed software systems: how to establish quickly, cheaply, and reliably whether they can deliver their intended performance before expending significant time, effort and money on detailed design and implementation. We describe ∆QSD, a novel metrics-based and quality-centric paradigm that uses formalised outcome diagrams to explore the performance consequences of design decisions, as a performance blueprint of the system. The distinctive feature of outcome diagrams is that they capture the essential observational properties of the system, independent of the details of system structure and behaviour. The ∆QSD paradigm derives bounds on performance expressed as probability distributions encompassing all possible executions of the system. The ∆QSD paradigm is both effective and generic: it allows values from various sources to be combined in a rigorous way, so that approximate results can be obtained quickly and subsequently refined. ∆QSD has been successfully used by Predictable Network Solutions for consultancy on large-scale applications in a number of industries, including telecommunications, avionics, and space and defence, resulting in cumulative savings worth billions of US dollars. The paper outlines the ∆QSD paradigm, describes its formal underpinnings, and illustrates its use via a topical real-world example taken from the blockchain/cryptocurrency domain. ∆QSD has enabled challenging throughput targets to be met for a globally distributed blockchain operating on the public internet.

Dioclea apurensis Kunth is native to ferruginous rocky outcrops (known as canga) in the eastern Amazon. Native cangas are considered hotspots of biological diversity and have one of the largest iron ore deposits in the world. There, D. apurensis can grow in post-mining areas where molecular mechanisms and rhizospheric interactions with soil microorganisms are expected to contribute to their establishment in rehabilitating minelands. In this study, we compare the root proteomic profile and rhizosphere-associated bacterial and fungal communities of D. apurensis growing in canga and a rehabilitating mineland to characterize the main mechanisms that allow the growth and establishment in post-mining areas. The results showed that proteins involved in response to oxidative stress, drought, excess of iron, and phosphorus deficiency were more accumulated in canga and, therefore, helped explain its high establishment rates in rehabilitating minelands. Rhizospheric selectivity of microorganisms was more evident in canga. The microbial community structure was mostly different between the two habitats, denoting that despite having its preferences, D. apurensis can associate with beneficial soil microorganisms without specificity. Therefore, its good performance in rehabilitating minelands can also be improved or attributed to its ability to cope with beneficial soil-borne microorganisms. Native plants with such adaptations must be used to enhance the rehabilitation process.

Bulukumba Regency, South Sulawesi, Indonesia is one of the centres for whiteleg shrimp, Litopenaeus vannamei production that applies intensive technology. However, no information has been obtained regarding the characteristics and status of water quality in coastal areas with environmentally friendly concepts and the potential to receive a waste load. The study aimed to determine the performance of whiteleg shrimp culture in relation to temporal and spatial aspects and characteristic and water quality status. Measurement and sampling of water were carried out before stocking/initial of culture whiteleg shrimp (rainy season) and end of culture/after harvesting of whiteleg shrimp (dry season) at two locations in the coastal area of ​​Bulukumba Regency, namely Bonto Bahari Subdistrict (BB) and Gantarang Subdistrict (GT). Variables measured and analyzed included temperature, salinity, pH, dissolved oxygen, nitrate, nitrite, ammonia, phosphate, total suspended solids, and total organic matter. Data analysis with descriptive statistics, multivariate statistics, and non-parametric statistics. The Storet (Storage and Retrieval) method was used to determine the water quality status. The results showed that the culture of whiteleg shrimp was technology-intensive with a stocking density of 110 - 220 ind/m² with productivity between 13.9 - 44.4 tons/ha/cycle. The predicted waste load of N is 28.00 tons/cycle and P reaches 6.61 tons/cycle. Another result was that changes in water quality status during the rainy season were classified as moderately polluted at the BB location and complying quality standards at the GT location, while in the dry season, both locations were categorized as heavily polluted. Variables of water quality that caused the decrease in water quality status in both locations (BB and GT) were observed to increase salinity, nitrate concentration, and ammonia concentration. However, there was a decrease in dissolved oxygen concentration in the dry season.

The last few decades have witnessed a surge of interest in adventure sports, and an emerging research focus on these activities. However, recent conceptual analyses and scientific reviews have highlighted a major, fundamental question that remains unresolved: what constitutes an adventure sport (and are they ‘sports’ at all)? Despite several proposals for definitions, the field still seems to lack a shared conceptualization. This deficit may be a serious limitation for research and practice, restricting the development of a more nuanced theoretical explanation of participation and prac-tical implications within and across adventure sports. In this article we address another crucial question, how can adventure sports be better understood for research and practice? We briefly summarize previous definitions to address evident confusion and lack of conceptual clarity in the discourse. Alternatively, we propose how an ecological perspective on human behaviors, as in-teractions with the environment, may provide an appropriate conceptualization to guide and enhance future research and practice, using examples from activities such as freeride skiing / snowboarding, white-water kayaking, climbing, mountaineering and the fields of sport science, psychology and avalanche research and education. We draw on ecological dynamics as a trans-disciplinary approach to discuss how this holistic framework presents a more detailed, nuanced, and precise understanding of adventure sports.

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

Metabolic and ionic changes during ischaemia predispose the heart to the damaging effects of reperfusion. Such changes and the resulting injury differ between immature and adult heart. Therefore, cardioprotective strategies for adults need to be tested in immature heart. We have recently shown that simultaneous activation of PKA and EPAC confers marked cardioprotection in adult hearts. The aim of this study is to investigate the efficacy of this intervention in immature hearts and determine whether the mitochondrial permeability transition pore (MPTP) is involved. Isolated perfused Langendorff hearts from both adult and immature rats were exposed to global ischaemia and reperfusion injury (I/R) following control perfusion or perfusion after an equilibra-tion period with activators of PKA and/or EPAC. Functional outcome and reperfusion injury were measured and in parallel, mitochondria were isolated following 5 min reperfusion to determine whether cardioprotective interventions involved changes in MPTP opening behaviour. Perfusion for 5 minutes preceding ischaemia of injury- matched adult and immature hearts with 5 µM 8-Br (8-Br-cAMP-AM), an activator of both PKA and EPAC, led to significant reduction in post-reperfusion CK release and infarct size. Perfusion with this agent also led to a reduction in MPTP opening propensity in both adult and immature hearts. These data show that immature hearts are innately more resistant to I/R injury than adults, and that this is due to a reduced ten-dency to MPTP opening following reperfusion. Further, simultaneous stimulation of PKA & EPAC causes cardioprotection which is additive to the innate resistance.

Mitochondria play key roles in cellular energy metabolism in eukaryotes. Mitochondria of most organisms contain their own genome and specific transcription and translation machineries. The expression of angiosperm mtDNA involves extensive RNA-processing steps, such as RNA trimming, editing, and the splicing of numerous group II-type introns. Pentatricopeptide repeat (PPR) proteins are key players of plant organelle gene expression and RNA metabolism. In the present analysis, we reveal the function of the MITOCHONDRIAL SPLICING FACTOR 2 gene (MISF2, AT3G22670) and show that it encodes a mitochondria-localized PPR protein that is crucial for early embryo-development in Arabidopsis. Molecular characterization of embryo-rescued misf2 plantlets indicates that the splicing of nad2 intron 1 and thus respiratory complex I biogenesis are strongly compromised. Moreover, the molecular function seems conserved between MISF2 protein in Arabidopsis and its orthologous gene (EMP10) in maize, suggesting that the ancestor of MISF2/EMP10 was recruited to function in nad2 processing before the monocot-dicot divergence, ~200 million years ago. These data provide new insights into the function of nuclear-encoded factors in mitochondrial gene expression and respiratory chain biogenesis during plant embryo development.

Shallow bathymetry inversion algorithms have long been applied in various types of remote sensing imagery with relative success. However, this approach requires that imagery with increased radiometric resolution in the visible spectrum is available. The recent developments in drones and camera sensors allow for testing current inversion techniques on new types of datasets. This study explores the bathymetric mapping capabilities of fused RGB and multispectral imagery, as an alternative to costly hyperspectral sensors. Combining drone-based RGB and multispectral imagery into a single cube dataset, provides the necessary radiometric detail for shallow bathymetry inversion applications. This technique is based on commercial and open-source software and does not require input of reference depth measurements in contrast to other approaches. The robustness of this method was tested on three different coastal sites with contrasting seafloor types. The use of suitable end-member spectra which are representative of the seafloor types of the study area and the sun zenith angle are important parameters in model tuning. The results of this study show good correlation (R2>0.7) and less than half a meter error when they are compared with sonar depth data. Consequently, integration of various drone-based imagery may be applied for producing centimetre resolution bathymetry maps at low cost for small-scale shallow areas.

Bearings are widely used in various types of electrical machinery and equipment. As their core components, failures will often cause serious consequences . At present, most methods of parameter adjustment are still manual adjustment of parameters. This adjustment method is susceptible to prior knowledge and easy to fall into the local optimal solution, failing to obtain the global optimal solution and requires a lot of resources.Therefore, this paper proposes a new method of bearing fault diagnosis based on wavelet packet transform and convolutional neural network optimized by simulated annealing algorithm.The experimental results show that the method proposed in this paper has a more accurate effect in feature extraction and fault classification compared with traditional bearing fault diagnosis methods. At the same time, compared with the traditional artificial neural network parameter adjustment, this paper introduces the simulated annealing algorithm to automatically adjust the parameters of the neural network, thereby obtaining an adaptive bearing fault diagnosis method. To verify the effectiveness of the method, the Case Western Reserve University bearing database was used for testing, and the traditional intelligent bearing fault diagnosis method was compared. The results show that the method proposed in this paper has good results in bearing fault diagnosis. Provides a new way of thinking in the field of bearing fault diagnosis in parameter adjustment and fault classification algorithms

Background Recently, a surge of COVID 19 was observed globally, regionally and nationally. With increasing numbers of cases, the frequency of long COVID is on the rise. Management and control of long COVID depend on changes in respect of human behaviors and requires an understanding of knowledge, attitudes, and practices (KAP) regarding health threats. MethodsA descriptive cross sectional study using online survey to gather data on the socio-economic background, knowledge, attitudes and practices on long-term complications of COVID. Results: Out of 201 respondents, 89.2% participants have heard about long-term complications of COVID 19. Only 35.9% have demonstrated adequate knowledge in the questions relating to co-morbidities and risk factors of COVID-19. A total of 92.2% believe that they should adhere to preventive measures following vaccination. Less than 60 % were following the advice on avoiding unnecessary travel and crowded places. Further, less than 50% were following COVID preventive measures. ConclusionAlthough the majority of participants have heard about long-term complications and common symptoms, the knowledge regarding co-morbidities that can lead to severe disease and long COVID was not satisfactory. The attitudes of the participants indicated increasing concern about long COVID. Practices indicate lack of adherence to key measures such as avoiding crowded places. These findings highlight the need for further increasing of awareness.

We study the μ-μ45-T phase diagram of the 2+1-dimensional Gross-Neveu model, where μ denotes the ordinary chemical potential, μ45 the chiral chemical potential and T the temperature. We use the mean-field approximation and two different lattice regularizations with naive chiral fermions. An inhomogeneous phase at finite lattice spacing is found for one of the two regularizations. Our results suggest that there is no inhomogeneous phase in the continuum limit. We show that a chiral chemical potential is equivalent to an isospin chemical potential. Thus, all results presented in this work can also be interpreted in the context of isospin imbalance.

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a significantly increased risk of cardiovascular mortality, mainly attributed to accelerated atherosclerosis. Methods: Thirty-two women (aged more than 18 years) with RA, and 25 age-matched healthy women were included in this study. Biomarkers of inflammation, red blood cells (RBCs) redox balance, estrogen receptor alpha (ER-α) expression as well as ERK 1/2 phosphorylation content were evaluated in RA patients at baseline and six months after treatment with disease modifying anti‐rheumatic drugs (DMARDs). Results: For the first times we demonstrated that in RA patients: i) disease activity score (DAS-28) positively correlated with RBC ER-α expression, and negatively with total antioxidant capacity of plasma; ii) RBC ER-α expression positively correlated with systemic inflammatory biomarkers and oxidative stress parameters as well as ERK 1/2 phosphorylation; and iii) DMARDs treatments improved the clinical condition measured by DAS-28 score decrease, although the RBCs appeared to be more prone to pro-oxidant status associated to the expression of survival molecules. Conclusion: Our data strongly suggest that RBCs could also participate in vascular homeostasis through fine modulation of an intracellular signal linked to the ER-α.

Water is essential for all living things however its pain has become serious. Many industrial activities cause its pollution by the release of polluting byproduct. Waste water treatment is hence necessary. In this context, the waste water of the textile industry containing Red Acid 52 was treated by the solid waste of the washed natural phosphate byproduct. Natural phosphate was also studied. The solid materials were first characterized by chemical analysis, Fourier Transform Infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The phosphate materials were after that, tested in the adsorption of the Red Acid 52. The experimental data indicated that the phosphate waste rock allowed the removal of Red Acid 52. Its maximum retention capacity attained 18.4 mg.g-1. Calcinations of materials inhibits the removal capacity found reduced by 60 to 70%. The adsorption kinetics of the Red Acid 52 on the material is well described by the pseudo second order model while the adsorption isotherms are identified by the Langmuir model. Hereafter, the thermodynamic study revealed that the adsorption process is spontaneous and exothermic. Keywords: Waste water, Phosphate co-product, Adsorption, Red Acid 52.

A general approach to substituted pyrrolidines via [3 + 2] 1,3-dipolar cycloaddition between nonstabilized azomethine ylides and cyanosulfones was developed. The efficient method provides a series of substituted pyrrolidines bearing a quaternary carbon center in high yields (up to 98%) excellent diastereoselectivities (up to &gt;25:1 dr) under ambient reaction conditions.

We describe a method for protein quantification and for mRNA quantification in small sample quantities of human induced pluripotent stem-cell-derived-cardiomyocytes (hiPSC-CMs). Demonstrated here is how the capillary-based protein detection system Wes^TM by ProteinSimple and the Power SYBR^TM Green Cells-to-CT^TM Kit by Invitrogen can be applied to individual samples in a 96-well microplate format and thus made compatible with high-throughput (HT) cardiomyocyte assays. As an example of the usage, we illustrate that Cx43 protein and GJA1 mRNA levels in hiPSC-CMs are enhanced when the optogenetic actuator, channelrodopsin-2 (ChR2), is genetically expressed in them. Instructions are presented for cell culture and lysate preparations from hiPSC-CMs, along with optimized parameter settings and experimental protocol steps. Strategies to optimize primary antibody concentrations as well as ways for signal normalization are discussed, i.e. antibody multiplexing and total protein assay. The sensitivity of both the Wes and Cells-to-CT kit enables protein and mRNA quantification in a HT format, which is important when dealing with precious small samples. In addition to being able to handle small cardiomyocyte samples, these streamlined and semi-automated processes enable quick mechanistic analysis.

Atmospheric lightning is an outcome of extreme complex physical processes occurring in the atmosphere. Cloud-to-ground (CG) lightning is considered as a natural disaster. Understanding the importance of CG lightning and implication of the lightning phenomena, Global Climate Observing System (GCOS), world meteorological organization, in its report in the year 2016, introduced the lightning as an Essential Climate Variable (ECV). The present report uses the Lightning Detection Sensor Network (LDSN) established by the National Remote Sensing Centre, Indian Space Research Organization over India to generate the Lightning ECV. A use case of these ECVs are also showcased for an event in Bihar, India, when 42 deaths were reported at locations with large number of CG occurrences.

The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40-60μm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have tremendous potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.

Timely crop yield forecasts at national level are substantial to support food policies, to assess agricultural production and to subsidize regions affected by food shortage. This study presents an operational crop yield forecasting system for Poland that employs freely available satellite and agro-meteorological products provided by the Copernicus programme. The crop yield predictors consist of: (1) vegetation condition indicators provided daily by Sentinel-3 OLCI (optical) and SLSTR (thermal) imagery, (2) a backward extension of Sentinel-3 data (before 2018) derived from cross-calibrated MODIS data, (3) air temperature, total precipitation, surface radiation, and soil moisture derived from ERA-5 climate reanalysis generated by the European Centre for Medium-Range Weather Forecasts. The crop yield forecasting algorithm is based on thermal time (growing degree days derived from ERA-5 data) to better follow the crop development stage. The recursive feature elimination is used to derive an optimal set of predictors for each administrative unit, which are ultimately employed by the Extreme Gradient Boosting regressor to forecast yields using official yield statistics as a reference. According to intensive leave-one-year-out cross validation for 2000–2019 period, the relative RMSE for NUTS-2 units are: 8% for winter wheat, and 13% for winter rapeseed and maize. Respectively, for the LAU units it equals 14% for winter wheat, 19% for winter rapeseed, and 27% for maize. The system is designed to be easily applicable in other regions and to be easily adaptable to cloud computing environments (such as DIAS or Amazon AWS), where data sets from the Copernicus programme are directly accessible.

The article deals with the current state of energy consumption and CO2 emissions in the urban area of building clusters. There are many requirements, such as those set by the EU (FIT 55, decarbonisation in 2050, full electromobility in 2035, or mandatory annual reductions in energy consumption and CO2 production) or societal requirements, such as stable energy supply and its optimisation while significantly reducing CO2 emissions. This inspired us to design an energy model of a building (EMB) with smart grid implementation in a decentralized sustainable energy system. Simulation model studies were carried out to show the possibility of their application in the process of fully satisfying energy needs in terms of reducing their environmental impact. A decentralized photovoltaic system (microgrid) connected to a distribution grid. The main objective is to propose an original methodology for the design of smart "Nearly Zero Energy Buildings" (NZEB) and a subsequent solution for energy sustainability. This has led us to use HOMER, PV*SOL, Monte Carlo and DesignBuilder software which were chosen from the range of options that were and are available. Subsequently, a synthesis of the selected software solutions was carried out and a new model - the "Energy Model of a Building" (EMB) - was proposed in the process of integration with the energy performance of buildings, as an original optimization basis for designing smart buildings and smart areas, and even cities. The proposed EMB has been verified and evaluated within the experiment.

Acute myeloid leukaemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most AMLs, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is therefore a valuable strategy to overcome the chemotherapy resistance of leukemic cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI), a well-known inhibitor of ROS production, in targeting AML cells. Results showed that although inhibiting cytoplasmic ROS production, DPI triggered an increase in the mitochondrial ROS levels caused by the disruption of the mitochondrial respiratory chain. We also demonstrated that DPI blocks the mitochondrial oxidative respiration (OxPhos) in a dose-dependent manner and that AML cells with high OxPhos status were highly sensitive to treatment with DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, our results suggest that targeting mitochondrial function by DPI might be exploited to target AML cells with high OxPhos status.

In this experimental work, pure nickel oxide and Al-doped NiO thin films have successfully been elaborated onto glass substrates by solar spray pyrolysis technique. The substrates were heated at around 450°C using a solar heater (furnace). The structural, optical and electrical properties of the elaborated Al-doped films have been studied at different atomic percentage ratios (0, 0.5, 1, 1.5 and 2 at. %). The results of Al-doped NiO films XRD patterns were, the formation of (NiO) phase under a cubic crystalline structure (polycrystalline) with a strong favored orientation along (111) plane were noticed at all sprayed films. When Al doping ratio reaches 1 at.%, an growth in crystallite size over 31.9 nm was obtained denoting the nano-structure of the product, which confirmed by SEM images. In addition, aluminum oxide Al₂O₃ was clearly observed at 1.5 at.% Al ratio. Otherwise, all thin films have a good optical transmission in the visible region of about 65%, the optical band gap energy decreased from 3.69 to 3.64 eV with increasing Al doping ratio. It is shown that the layer deposited with 0.5 at.% has less disorder with few defects. The investigation on electrical properties of elaborated thin films confirmed that the conductivity of NiO films was improved, after doping them with Al which affirms their p-type character of semiconductor. However, an addition of an excessive quantity of Al content causes the formation of Al₂O₃ which leads to a decrease in the conductivity. It is worth mentioning that the Al content of 0.5 at.% is the optimum ratio in terms of electrical conductivity and formation defect. Al-doped NiO can be used in various optoelectronic devices due to its good transparency and high electrical conductivity.

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

The efficacy of the product development process is measured by the ability to launch a project with product and production process specifications that could guarantee that the manufacturing can produce it with the least impact. If a problem is detected late, they bring consequences beyond the high cost of the solution, if related to physical ergonomics, which will influence the well-being of operators, productivity, and quality. Virtual Reality (VR) and Digital Human Modeling (DHM) are ones of the enabling technologies of Industry 4.0 and has already been applied on a large scale in industries such as automotive, construction, and aeronautics. However, even though the huge applications, these technologies are not yet applied by these industries for the analysis of physical ergonomics during product development phases. This study aims to characterize the state of the art and technology about the application of Virtual Reality and Digital Human Modeling for the physical ergonomics analysis in the during product development phases in the industry through a systematic review of the literature and patents. In patent documents recovery, we used Derwent Innovation database. The research is based on searching the selected terms in the title, summary, and claims of the documents through a search strategy containing IPC code and keywords. In articles recovery, we searched ScienceDirect, Springer, and IEEExplore databases for scientific publications. The search resulted in 311 patents documents and 16 articles in the scientific database. This study analyzed the patents to map out the technological progress in this area, where we found in the charts and data an increasing number of publications per year and a spread application with a considerable number of new technologies presented in these recent patents. The literature review indicated that Virtual Reality technology complements the Digital Human Modeling during physical ergonomics analysis for manufacturing process already designed. The majority of research on the use of VR and DHM technologies for physical ergonomics analysis focus on the automotive industry and the ergonomic assessment of workstations and current processes. Further research is needed to investigate how Virtual Reality and Digital Human Modeling might assist in the understanding of physical ergonomics in certain tasks throughout the product development process, such as the simulation of worker posture or effort when assembling parts.

Ascending aorta aneurysm (AsAA) is a complex disease, currently defined an inflammatory disease. In the sporadic form, AsAA has, indeed, a complex physiopathology with a strong inflammatory basis, significantly modulated by genetic variants in innate/inflammatory genes, acting as independent risk factors and as largely evidenced in our recent studies performed during the last 10 years. Based on these premises, here, we want to revise the impact of reactive oxygen species (ROS) and oxidative stress on AsAA pathophysiology and consequently on the onset and progression of sporadic AsAA. This might consent to add other important pieces in the intricate puzzle of the pathophysiology of this disease with the translational aim to identify biomarkers and targets to apply in the complex management of AsAA, by facilitating the AsAA diagnosis currently based only on imaging evaluations, and the treatment exclusively founded on surgery approaches.

MicroRNA-155 (miR-155) expression promotes inflammatory responses in macrophages. Activation of macrophages with lipopolysaccharide (LPS) elevates miR-155, while the anti-inflammatory cytokine interleukin-10 (IL10) reduces miR-155 levels. MiR-155 exists in two forms, miR-155-5p and miR-155-3p, produced from the precursor of miR-155 (pre-miR-155). MiR-155-5p is the most abundant strand in activated macrophages, but in response to LPS, the miR-155-3p level is upregulated first, followed by miR-155-5p later. We have previously identified CELF2 protein which interacts with pre-miR-155 and impairs miR-155-5p expression. We now show that CELF2 only regulates the miR-155-5p expression and that another protein FUBP1 controls miR-155-3p levels in response to LPS and IL10.

Cystic Fibrosis is a rare genetic disease that affects the transmission of chloride ions due to mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Even though there are nearly 2000 mutations identified to be related to the condition, the most common mutation is F508del; deletion of a phenylalanine residue at 508. On the other hand, G542X which is a Class I mutation is also found very commonly and there are no modulator treatments available for it. Furthermore, it was investigated that R553X mutation can as well be corrected simultaneously with G542X mutation. Therefore, the main focus is on designing a gene therapy project that can correct all these three mutations at once by utilizing the prime editing technique via lipid-based delivery. In this way, the mutations can be edited through plasmids that were designed containing 2 pegRNAs and the Cas enzyme. To implement such an approach efficiently, both ex vivo, an animal model, and in vivo steps are to be designed. For the cell line, fibroblasts are selected due to their simplicity and low cost. The animal model of the experiment is determined to be a ferret concerning the high similarity to the human's CFTR protein and finally, the procedure will follow on a direct application in human Cystic Fibrosis patients. The plasmids are thought to be delivered through a cationic liposome that will reach the lungs with the aid of a nebulizer. At the last stage of the experimental procedure, Sanger Sequencing will be done to see if the desired edit within the CFTR has been performed successfully, and Next Generation Sequencing will be executed to see if there has been an off-target mutation in the remainder of the genome. Whereas for detecting the presence and expression of CFTR protein in humans, immunodetection with flow cytometry will be conducted.

A newly-discovered physical mechanism involving electron tunneling in layers of the protein ferritin that are found in catecholaminergic neurons (catecholaminergic neuron electron transport or CNET), is hypothesized to support communication between neurons. Recent tests further confirm that these ferritin layers can also perform a switching function (in addition to providing an electron tunneling mechanism) that could be associated with action selection in those neurons, consistent with earlier predictions based on CNET. While further testing would be needed to confirm the hypothesis that CNET allows groups of neurons to communicate and act as a switch for selecting one of the neurons in the group to assist in reaching action potential, this paper explains how that hypothesized behavior would be consistent with Integrated Information Theory (IIT), one of a number of consciousness theories (CTs). While the sheer number of CTs suggest that any one of them is not sufficient to explain consciousness, this paper demonstrates that CNET can provide a physical substrate that is consistent with IIT and which can also be applied to other CTs, such as to conform them into a single explanation of consciousness.

Direct interaction with the neuronal cells is a prerequisite to deciphering useful information in understanding the underlying causes of diseases and functional abnormalities in the brain. Precisely fabricated nanoelectrodes provide the capability to interact with the brain in its natural habitat without compromising its functional integrity. Considerable research has been focused on the employment of vertical nanotubes as nanoelectrodes due to large-scale intracellular recording capability and longer-term intracellular access that arise from their unique geometry. Despite many types of nanotube structures reported in the literature, a limited subset of the nanotubes has been investigated for neural interfacing. This work reports on the fabrication and optimisation of vertically oriented titania nanotube arrays as a scalable electrode platform for neural interface application. To this end, the doping was performed by incorporating a selected group of biologically active metallic ions, including zinc, strontium, and copper, into TiO2 lattice and its effect was studied with respect to the structural, electrochemical and biological properties of the nanotube arrays. It was found that doping can change the length, diameter and wall thickness of the nanotubes. Among pure and doped samples, the copper-doped TiO2 nanotubes demonstrated the highest electrochemical and biological performance. Our results suggest that the doping can be used as a promising method to optimise the properties of nanotube arrays for the development of high-performance neural electrodes.

Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of neurotoxin-induced PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD, and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.

The Life Cycle Analysis (LCA) was used to assess the impact of biomethane plant of the “La Católica” in Pedregal-Majes-Arequipa farm, fed with cow manure and holding a production of 60 Nm3/day of purified biogas. Life cycle inventory, impact assessment and interpretation were performed. The functional unit established was 1 MJ of energy produced; the study was modeled with SimaPro software, Ecoinvent Database and ReCiPe Midpoint (H) impact assessment methodology, according to the impact categories of climate change and fossil resource depletion. The impact analysis was limited to the Well to Tank (WTT) approach, which involves feedstock transport, substrate mixed, anaerobic digestion, biogas purification, storage and injection of the fuel into transport vehicles. The digestion process generated the highest amount of CO2 emissions (1.79E-02 kg CO2 eq/MJ-biomethane) and the highest depletion of fossil resources (6.58E-03 kg oil eq/MJ-biomethane), compared to the other fuel production, due to energy consumption and transport infrastructure. Biomethane was then compared to fossil fuels, resulting in natural gas generating the least amount of CO2 emissions, followed by diesel and finally biomethane. For the fossil resource depletion category, biomethane presented the lowest amount of fossil fuel consumption (1.37E-02 kg oil eq/MJ-biomethane), followed by natural gas and diesel.

Huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five αv-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small molecule against αvβ1 is undergoing a clinical trial for NASH-associated fibrosis as a rare reagent aiming at fibrogenesis. Latent TGFβ activation, a distinct talent of αv-integrins, has been intriguing as therapeutic target. None of the αv-integrin inhibitors, however, has been in the clinical market. αv-integrins commonly recognize an Arg-Gly-Asp (RGD) sequence, and thus the pharmacophore of inhibitors for the 5-integrins is based on the same RGD structure. The RGD preference of the integrins, at the same time, dilutes ligand specificity, as the 5-integrins share ligands containing RGD sequence such as fibronectin. With the inherent little specificity in both drugs and targets, “disease specificity” has become less important for the inhibitors than blocking as many αv-integrins. In fact, an almighty inhibitor for αv-integrins, pan-αv, was in a clinical trial. On the contrary, approved integrin inhibitors are all specific to target integrins, which are expressed in cell-type specific manner: αIIbβ3 on platelets, α4β1, α4β7 and αLβ2 on leukocytes. Herein, “disease specific” integrins would serve as attractive targets. α8β1 and α11β1 are selectively expressed in hepatic stellate cells (HSCs) and distinctively induced upon culture activation. The exceptional specificity to activated HSCs reflects rather “pathology specific” nature of these new integrins. The monoclonal antibodies against α8β1 and α11β1 in preclinical examinations may illuminate the road to the first medical reagents.

Cytosine (C) to uracil (U) RNA editing is one of the most important post-transcriptional processes, however exploring C-to-U editing events efficiently within the crop mitochondrial genome remains a challenge. An improving predictive RNA editor for crop mitochondrial genomes, iPReditor-CMG, was proposed, which was based on SVM, three common crop mitochondrial genomes and self-sequenced tobacco mitochondrial ATPase. After multi-combination feature extracting, high-dimension feature screening and multi-test independent predicting, the results showed that the average accuracy of intraspecific prediction was 0.85, and the highest value even up to 0.91, which outperformed the previous reference models. While the prediction accuracies were 0.78 between dicotyledons and no more than 0.56 between dicotyledons and monocotyledons, implying a possible similarity in C-to-U editing mechanisms among close relatives. The best model was finally identified with an independent test accuracy of 0.91 and an area under the curve of 0.88, and further suggested that five unreported feature sequences TGACA, ACAAC, GTAGA, CCGTT and TAACA were closely associated with the editing phenomenon. Multiple evaluation findings supported that the iPReditor-CMG could be effectively applied to predict crop mitochondrial editing sites, which may contribute to insight into their recognition mechanisms and even other post-transcriptional events in crop mitochondria.

Management of Juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex also in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA registered in clinicaltrials.gov and clinicaltrialsregister.eu concerning sponsoring, enrollment, duration, localization, and particularly objectives. Close of database was 7 January 2021. After identifying doubled-registered studies, N=72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% by pharma industry. The majority of studies was of interventional type (77.8%), while others (22.2%) were observational. Median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. Duration differed remarkably from one month to more than 15 years with a median of 42.5 months. 61.1% of studies were located in a single country, 38.9% were in several. Europe and North America clearly dominated study localizations. Study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues like systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role.