Enzyme replacement therapy (ERT) improves the somatic manifestations in mucopolysaccharidoses (MPS))．However, because intravenously administered enzymes cannot cross the blood brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT intend to achieve CNS effects, but the burdens on patients are inimical to long-term multiple administrations. However, after pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in mice model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the hitherto obtained preclinical and clinical evidence associated with this drug, and discusses the preclinical, translational and clinical challenges of evaluating, ameliorating and preventing the neurodegeneration in patients with MPS-II.

Breast cancer (BC) is the most common type of cancer in both men and women alike, but it is more prevalent in women. Natural compounds that can modulate the oncogenic process can be considered a significant anti-cancer agent for treating BC. These natural compounds are more effective than synthetic drugs, which have profound side effects on the normal cell and resistance to cancer cells. Genistein is a type of dietary phytoestrogen included in the flavonoid group with a similar structure of estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutics drugs. Several research studies demonstrated that it can target the estrogen receptor (ER), Human epidermal growth factor receptor-2 (HER2), and Breast cancer gene-1 (BRCA-1) in multiple BC cell lines, as well as sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. Genistein effectively showed anti-cancer activities through apoptosis induction, arresting cell cycle, inhibiting angiogenesis with metastasis, reducing inflammation, mammosphere formation, tumor growth, up-regulating tumor suppressor gene, and downregulating oncogene in suppressing cancer progression in vitro and animal model study. In addition, research studies have also suggested that these phytochemicals synergistically reverse the resistance mechanism of chemotherapeutic drugs, increasing the efficacy of some chemoinformatics drugs. Our review article aims to unbox and validate the molecular pharmacology in breast tissue, cell-specific anti-cancer mechanism with synergistic activity, and possible pharmacokinetic parameters of Genistein as a potential alternative therapeutic option for the treatment of BC.

Various studies have addressed the role of neutrophils in cancer wherein the focus has been drawn on the elevated neutrophil count in blood or at tumor loci. However, cancer has a systemic impact which targets various organs thus challenging the overall physiology of the host. So, it is worthwhile to explore whether and how neutrophils contribute to systemic deterioration in cancer. To discern the systemic role of neutrophils, we monitored their number and function at different stages of tumor growth in Dalton’s lymphoma mice model. Notably, we observed a gradual increase in neutrophil count in blood and their infiltration in vital organs of tumor bearing mice. In parallel, we observed damaged histoarchitecture with significant alterations in biochemical parameters that aggravated with tumor progression. We next examined systemic impact of neutrophil by assessing neutrophil elastase, myeloperoxidase, and matrix metalloproteinases (MMP-8 and MMP-9) wherein we found their upregulated expression and activity in tumor condition. Taken together, our results demonstrate high infiltration and hyperactivation of neutrophils which possibly account for gradual systemic deterioration during cancer progression. Our findings thus implicate neutrophils as a potential therapeutic target that may help to reduce the overall fatality rate of cancer.

The genetic diversity of foot-and-mouth disease virus (FMDV) poses a challenge to the successful control of the disease, and it is important to identify the emergence of different strains in endemic settings. The objective of this study was to evaluate sampling of clinically healthy livestock at slaughterhouses as a strategy for genomic FMDV surveillance. Serum samples (n = 11875) and oropharyngeal fluid (OPF) samples (n = 5045) were collected from asymptomatic cattle and buffalo on farms in eight provinces in southern and northern Vietnam (2015 to 2019) to characterize viral diversity. Outbreak sequences were collected between 2009 and 2019. In two slaughterhouses in southern Vietnam, 1200 serum and OPF samples were collected from asymptomatic cattle and buffalo (2017 to 2019) as a pilot study on the use of slaughterhouses as sentinel points of surveil-lance. VP1 sequences were analyzed using discriminant principal component analysis and time-scaled phylodynamic trees. Six of seven serotype O and A clusters circulating in southern Vietnam from 2017-19 were detected at least once in slaughterhouses, sometimes pre-dating outbreak sequences associated with the same cluster by 4-6 months. Routine sampling at slaughterhouses may provide timely and cost-effective strategy for genomic surveillance to identify circulating and emerging FMDV strains.

Atomic state preparation can benefit from a compact and uniform magnetic field source. Simulations and experimental measurements have been used to design, build, and test such a source as shown by optical pumping of atomic Helium. This source is a 9.5 mm (3/8") OD x 6.7 mm (1/4") ID x 9.5 mm (3/8") long, NdFeB-N42 assembly of 1.6 mm (1/16") thick customized annular magnets. It has octopole decay with a residual dipole far field from imperfect dipole cancelations. It has greater than 50% clear aperture with uniform and collimated magnetic field consistent with the prediction of several models. Octopole roll-off localizes the field minimizing the need for shielding in applications. The device is applied to a high precision 3,4He laser spectroscopy experiment using σ+ or σ- optical pumping currently resulting in a measured 99.3% preparation efficiency and in accordance with a rate-equation model.

In 2008, Ecuador recognized the Constitutional Rights of Nature in a global first. This recognition implies a major shift in the human-nature relationship, from one between a subject with agency (humans) and an exploitable object (Nature), to a more equilibrated relationship of respect. However, the lack of a standard legal framework has left room for subjective interpretations and variable implementation. The recent widespread concessioning of pristine ecosystems to mining industries in Ecuador has set up an unprecedented conflict and test of these rights. Currently, a landmark case involving Los Cedros Protected Forest and mining companies has reached the Constitutional Court of Ecuador. If Ecuador’s highest Court rules in favor of Los Cedros and the Rights of Nature, it would set a legal precedent with enormous impact on biological conservation in Ecuador and, potentially, the world. Such a policy shift offers a novel conservation strategy, through citizen oversight and action.

Background: Gastric cancer (GC) is one of the leading malignancy diseases worldwide, especially in Asian. CAST is a potential oncogene in GC carcinogenesis process. The character of macrophage infiltration in GC microenvironment was also unaddressed. Methods: We first applied machine searching in gene candidate evaluation of GC. CAST expression was analyzed via the Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Protein-protein interaction (PPI) network was downloaded from STRING. We investigated the impact of CAST on clinical prognosis using Kaplan-Meier plotter. The correlations between CAST and Lgr5 and macrophage infiltration in GC was surveyed via TIMER 2.0. Finally, GeneMANIA was also used to evaluate the possible functional linkage between genes. Results: After machine-assisted searching, CAST expression was found signicant difference in the overall survival of GC patients. STRING revealed CAST related proteomics and transcriptomics associations, mainly about CAPN family. Moreover, CAST significantly impacts the prognosis of GC from other datasets validation. Notably, high CAST expression was correlated with worse overall survival in GC patients (hazard ratio = 1.59; logrank P = 9.4 x 10-8). CAST and Lgr5 expressions were both positively correlated with WNT 2 and WNT 2B. Among GC patients in several datasets, CAST and macrophage infiltration evaluated together showed no obvious trend toward poor clinical overall survival. Conclusion: CAST plays an important role in GC clinical prognosis and is associated with WNT 2/WNT 2B/Lgr5. Our study denmostrated that CAST in GC overall survival is regulated by macrophage infiltration.

Clove (Syzygium aromaticum L. Myrtaceae) is an aromatic plant widely cultivated in tropical and subtropical countries, rich in volatile compounds and antioxidants such as eugenol, β-caryophyllene, and α-humulene. Clove essential oil has received considerable interest due to its wide application in the perfumery, cosmetic, health, medical, flavoring, and food industries. Clove essential oil has relevant biological activities to human health, including antimicrobial, antioxidant, and insecticide. This review describes the effect of the extraction method (hydrodistillation, steam distillation, ultrasound-assisted extraction, microwave-assisted extraction, cold pressing, and supercritical fluid extraction) on the chemical composition of essential oil and its correlation with their biological activities. Likewise, are summarized the main compounds and their reported biological activities. Furthermore, the main applications in clove essential oil in the food industry are presented. Finally, this review presents the new biological activities such as anti-inflammatory, analgesic, anesthetic, antinociceptive and anticancer, which are beneficial for human health. This review aims to compile the effect of different methods of extracting clove essential oil on chemical composition, food applications, as well as a current description of biological activities of interest to human health. Biological activities have increased interest in research into this essential oil and its future applications in the food or pharmaceutical industry.

Climate risk is one of the confronting factors in Indian agriculture. To overcome this distrust, a large number of sensors can be installed in the fields,The extensive IoT platform can process the data sent by these sensors.The Data stream can be processed in real-timeusing Fuzzylogic, to offer smart solution. Network coding can enhance throughput and security. Thus reducing human interaction and improve efficiency.

This study focused on the characterization of lactic acid bacteria (LAB) in a renowned traditional Italian cheese, Pecorino di Farindola, to select an autochthonous culture and investigate its po-tential for the improvement of safety and functional properties. Two hundred and six LAB isolated throughout production and maturation from nine cheese lots of three farms were identified by 16S rRNA gene sequencing and tested for the presence of genes encoding virulence factors, vancomycin resistance (for enterococci), biogenic amines (BAs) and bacteriocin production, for antimicrobial activity, and for the capacity to survive in the gastro-intestinal tract (GIT) based on tolerance to low pH and bile salts and adhesion to CaCo-2 cells. A Lacticaseibacillus paracasei isolate was used in cheese making and determined a decline of spiked Listeria monocytogenes and Escherichia coli O157 faster than in control cheese. The autochthonous bacterial groups were numerically unaffected, apart from lactobacilli that were recovered in higher numbers in the cheese with added L. paracasei. Based on Repetitive Extragenic Palyndrome (Rep) PCR profiles, the added strain possibly dominated until day 88 in cheese. Results encourage further trials with autochthonous cultures to efficiently inhibit hazardous bacteria and enrich a functional microbiota in Pecorino di Farindola and similar cheeses.

The work presents the results of numerical fatigue analysis of a turbine engine compressor blade, taking into account the values of initial stresses resulting from surface treatment - shot-peening. The values of the residual stresses were estimated experimentally using X-ray diffraction. The paper specifies the values of the residual stresses on both sides of the blade and their reduction due to the cutting through the blade - relaxation. The obtained values of the residual stresses were used as initial stresses in the numerical fatigue analysis of the damaged compressor blade, which is subjected to resonant vibrations of known amplitude. Numerical fatigue ε-N life analysis was based on the several fatigue material models: Manson’s, Mitchell’s, Baumel-Seeger’s, Muralidharan-Manson’s, Ong’s, Roessle-Fatemi’s and Median’s, and also on the three models of cyclic hardening: Manson’s, Xianxin’s, and Fatemi’s. Because of this approach, it was possible to determine the relationship between the selection of the fatigue material ε-N model and the cyclic hardening model on the results of the numerical fatigue analysis. Additionally, the calculated results were compared with the results of experimental research, which allowed for a substantive evaluation of the obtained results. These results are of great scientific and practical importance. The problem of determining the fatigue life of blades with defects operating under resonance vibrations is one of the original tasks in the field of fracture mechanics and experimental mechanics. The results obtained are of great importance in the aviation industry and can be used during engine maintenance and inspections to assess the suitability of blades with defects in terms of the needs of further work. This aspect of engineering maintenance is of great importance from the aircraft safety point of view.

Climate risk is one of the confronting factors in Indian agriculture. To overcome this distrust, a large number of sensors can be installed in the fields,The extensive IoT platform can process the data sent by these sensors.The Data stream can be processed in real-timeusing Fuzzylogic, to offer smart solution. Network coding can enhance throughput and security. Thus reducing human interaction and improve efficiency.

Introduction: People with schizophrenia have poor cardiometabolic health, with elevated 10-year cardiovascular disease risk (CVD-R) scores and poor quality of life (QOL). There is lack of understanding of these issues in early psychosis. Aims: To quantify CVD-R in people with early psychosis and profile their obesity prevalence, lifestyle behaviours and QOL. Secondary aim was to explore associations between lifestyle behaviours/treatment characteristics and CVD-R/QOL. Method:Baseline data from 81 RCT participants were used to profile cardiometabolic health risks (QRISK®3, BMI and waist circumference). Participants self-reported lifestyle behaviours and QOL. Relationships between modifiable treatment/lifestyle factors and QOL/CVD-R were explored using bivariate analyses. Results: Participants’ relative risk for CVD over 10 years was 1.93 times higher than healthy counterparts; 39% also had an obese BMI and physical QOL was poor. No significant associations were observed between CVD-R or QOL with treatment characteristics and lifestyle factors. Discussion: Despite positive lifestyle behaviours, participants had elevated CVD-R scores and poor physical health related QOL. Quantifying CVD-R with QRISK®3 may highlight the need for health promotion interventions. Implications for practice: Mental health professionals should be alert to elevated cardiometabolic health risks in early psychosis, particularly as these can occur in the context of relatively healthy lifestyle behaviours.

Carthamin potassium salt isolated from Carthamus tinctorius L. was purified by an improved traditional Japanese method, without using column chromatography. The 1H and 13C nuclear magnetic resonance (NMR) signals of the pure product were fully assigned using one- and two-dimensional NMR spectroscopy, while the high purity of the potassium salt and deprotonation at the 3’ position of carthamin were confirmed by atomic adsorption spectroscopy and nano-electrospray ionization mass spectrometry.

Understanding of the decisive role of the interaction mechanism and kinetics in the combustion processes is highly relevant for the elaboration of optimal conditions for obtaining Mo-Cu composite powders. From this perspective, the efficient delivery of the reduction mechanism of copper and molybdenum oxides with combined Mg + C reducing agents at high heating rates is crucial to develop a valuable approach for the combustion synthesis of Mo-Cu composite powders. Herein, we shed light on the mechanism of the reactions in all the studied binary, ternary and quaternary systems contemporaneously demonstrating the effect of the heating rate on the conversion degree. The combination of two highly exothermic and speedy reactions (MoO3+3Mg and CuO+Mg vs MoO3+CuO+4Mg) led to a slow interaction with weak self-heating (dysynergistic effect) due to a change in the reaction mechanism. On the other hand, it has been shown that during the simultaneous utilization of the Mg and C reducing agents, the process begins exclusively with carbothermic reduction, and at relatively high temperatures it continues with magnesiothermic one. The effective activation energy values of the magnesiothermic stages of the studied reactions were determined by Kissinger isoconversional method.

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, which represents a critical and abundant population in most solid tumours microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

Molecular mechanisms associated with the pathogenesis of Vesicular stomatitis virus (VSV) in livestock remain poorly understood. Several studies have highlighted the relevant role of macrophages in controlling the systemic dissemination of VSV during infection in different animal models, including mice, cattle and pigs. To gain more insight on the molecular mechanisms used by VSV to impair the immune response in macrophages, we used microarrays to determine the transcriptomic changes produced by VSV infection in primary cultures of porcine macrophages. The results indicated that VSV infection induced the massive expression of multiple anorexic, pyrogenic, proinflammatory and immunosuppressive genes. Overall, the interferon (IFN) response appeared suppressed, leading to the absence of stimulation of interferon-stimulated genes (ISG). Interestingly, VSV infection promoted the expression of several genes known to downregulate the expression of IFNb. This represents an alternate mechanism for VSV control of the IFN response, beyond the recognized mechanisms mediated by the matrix protein. Although there was no significant differential gene expression in macrophages infected with a highly virulent epidemic strain compared to a less virulent endemic strain, the endemic strain consistently induced higher expression of all upregulated cytokines and chemokines. Collectively, this study provides novel insights into VSV molecular pathogenesis and immune evasion that warrants further investigation

Vertically aligned Fe, S, and Fe-S doped anatase TiO₂ nanotube arrays are prepared by electrochemical anodization process using an organic electrolyte in which lactic acid is added as an additive. In the electrolyte, nanotube layers of greater length (12 μm) and high order with inner diameter of approx. 90 nm and outer diameter of approx. 170 nm are achieved. Doping of Fe, S, and Fe-S via simple wet impregnation method substituted Ti and O sites with Fe and S, which leads to enhance the rate performance at high discharge current densities. Discharge capacities of TiO₂ tubes increased from 82 mAh g-1 (bare) to 165 mAh g-1 for Fe-S doped TiO₂ at high current densities of 0.3 mAcm-2 after 100 cycles with exceptional capacity retention of 85% after 100 cycles. Owing to the enhancement of thermodynamic and kinetic properties by doping of Fe-S, Li-diffusion increas2ed resulting in remarkable discharge capacities of 143 mAh g-1 and 89 mAh g-1 at a current density of 7.4 mA cm-2 and 19 mA cm-2, respectively.

Data sets for medical images are generally imbalanced and limited in sample size because of high data collection costs, time-consuming annotations, and patient privacy concerns. The training of deep neural network classification models on these data sets to improve the generalization ability does not produce the desired results for classifying the medical condition accurately and often overfit the data on the majority of class samples. To address the issue, we propose a framework for improving the classification performance metrics of deep neural network classification models using transfer learning: pre-trained models, such as Xception, InceptionResNet, DenseNet along with the Generative Adversarial Network (GAN) – based data augmentation. Then, we trained the network by combining traditional data augmentation techniques, such as randomly flipping the image left to right and GAN-based data augmentation, and then fine-tuned the hyper-parameters of the transfer learning models, such as the learning rate, batch size, and the number of epochs. With these configurations, the Xception model outperformed all other pre-trained models achieving a test accuracy of 98.7%, the precision of 99%, recall of 99.3%, f1-score of 99.1%, receiver operating characteristic (ROC) - area under the curve (AUC) of 98.2%.

The wide use of cadmium (Cd) in industry causes great environmental health problems to humans and animals. The aim of this study was to investigate the protective effects of Xylopia aethiopica fruit ethanol extract (XAFEE) on cadmium-induced inflammation and dyslipidemia in male albino rats. Thirty albino rats weighing 120–180 g were randomly selected into six groups (n = 5): control rats (administered distilled water only), Cd alone group (10 mg/ kg bw), Cd + 150 mg/kgbw XAFEE, Cd + 300 mg/kgbw XAFEE, 150 mg/kgbw XAFEE and 300 mg /kgbw XAFEE groups after 2-week acclimatization. The experiment lasted for 21 days, after which blood sample was collected by cardiac puncture. Changes in tumor necrosis factor (TNF-α), interleukin 10 (IL-10), total cholesterol (TC), triacylglycerol (TAG), phospholipids and free fatty acids (FFAs) concentrations in serum were determined. The results of the present study indicated that Cd exposure remarkably increased (p < 0.05) the TC, TAG, phospholipids, FFAs and TNF-α concentrations, and significantly decreased IL-10 concentration (p < 0.05). These findings suggest that inflammatory changes and alterations in lipid metabolism might be one of the mechanisms underlying the subtle effects of Cd toxicity, “dyslipidemia.” XAFEE expressed protective role against toxic influence of Cd on affected parameters in rats. The results raised the possibility of Xylopia aethiopica fruit being considered as a condiment in soup, local drinks, supplements or herbs preparations in areas where there are chances of Cd exposure, occupationally or environmentally.

Medicinal plants possess a surplus of novel and biologically active secondary metabolites that are responsible for counteracting diseases. Traditionally, Gomphandra tetrandra (Wall.) Sleumer is used to treat mental disorders. The present research was designed to explore phytochemicals from the ethanol leaf extract of Gomphandra tetrandra (Wall.) Sleumer to identify the potential pharmacophore(s) in the treatment of neurological disorders. The chemical compounds of the experimental plant were identified through GC-MS analysis. Besides, in-vitro antioxidant activity was assessed using different methods. Furthermore, in-vivo neurological activity was assessed in Swiss-albino mice. Computer aided analysis was appraised to determine the best-fit phytoconstituent of a total of fifteen identified compounds in the experimental plant extract against beta-amyloid precursor protein. The experimental extract revealed fifteen compounds in GC-MS analysis and the highest content was 9, 12, 15-octadecatrienoic acid (Z, Z, Z). Also, the extract showed potent anti-oxidant activity in in-vitro assays. Furthermore, in in-vivo neurological assays, the extract disclosed significant (p<0.05) neurological activity. The most favorable phytochemicals as neurological agents were selected via ADMET profiling and molecular docking was studied with beta-amyloid precursor protein. Moreover, in the computer aided study, 1, 5-Diphenyl-2H-1, 2, 4-triazoline-3-thione (Pub Chem CID: 2802516) was more active than other identified compounds with strong binding affinity to beta-amyloid precursor protein. The present in vivo and in silico studies revealed neuropharmacological features of G. tetrandra leaves extract as a natural agent against neurological disorders, especially Alzheimer’s disease.

Leishmania major is the main causative agent of cutaneous leishmaniasis in humans. The Friedlin strain of this species (LmjF) was chosen when a multi-laboratory consortium undertook the objective of deciphering the first genome sequence for a parasite of the genus Leishmania. The objective was successfully attained in 2005, and this represented a milestone for Leishmania molecular biology studies around the world. Although the LmjF genome sequence was done following a shotgun strategy and using classical Sanger sequencing, the results were excellent and this genome assembly served as the reference for subsequent genome assemblies in other Leishmania species. Here, we present a new assembly for the genome of this strain (named LMJFC for clarity), generated by the combination of two high throughput sequencing platforms, Illumina short-read sequencing and PacBio Single Molecular Real-Time (SMRT) sequencing, which provides long-read sequences. Apart from resolving uncertain nucleotide positions, several genomic regions have been reorganized and a more precise composition of tandemly repeated gene loci was attained. Additionally, the genome annotation has been improved by adding 542 genes and more accurate coding-sequences defined for around two hundred genes, based on the transcriptome delimitation also carried out in this work. As a result, we are providing gene models (including untranslated regions and introns) for 11,238 genes. Genomic information ultimately determines the biology of every organism; therefore, our understanding of molecular mechanisms will depend on the availability of precise genome sequences and accurate gene annotations. In this regards, this work is providing an improved genome sequence and updated transcriptome annotations for the reference L. major Friedlin strain.

Apoptosis is associated with numerous phenotypical characteristics, and is thus studied with many tools. In this study, we compared two broadly used apoptotic assays: TUNEL and staining with an antibody targeting the activated form of an effector caspase. To compare them, we developed a protocol based on commonly used tools such as filters, zprojection and thresholding. Even though it is commonly used in imageprocessing protocols, thresholding remains a recurring problem. Here we analyzed the impact of processing parameters and readout choice on the accuracy of apoptotic signal quantification. Our results show that TUNEL is quite robust, even if image processing parameters can allow or not to detect subtle differences of the apoptotic rate. On the contrary, images from anticleaved caspase staining are more sensitive to handle and proved to necessitate to be processed more carefully. We then developed an open source Fiji macro automatizing most steps of the image processing and quantification protocol. It is noteworthy that the field of application of this macro is wider than apoptosis as it can perfectly be used to treat and quantify other kind of images.

Urban Tree Canopy (UTC) greatly enhances the livability of cities by reducing urban heat buildup, mitigating stormwater runoff, and filtering airborne particulates, among other ecological services. These benefits, combined with the relative ease of measuring tree cover from aerial imagery, have led many cities to adopt management strategies based on UTC goals. In this study, we conducted canopy analyses for the 300 largest cities in Florida to assess the impacts of development practices, urban forest ordinances, and hurricanes on tree cover. Within the cities sampled, UTC canopy ranged from 5.9% to 68.7% with a median canopy coverage of 32.3% Our results indicate that the peak gust speeds recorded during past hurricanes events were a significant predictor of canopy coverage (P-value = <0.001) across the sampled cities. As peak gust speeds increased from 152 km/h (i.e., a lower-intensity Category 1 storm) to 225 km/h (lower-intensity Category 4 and the maximum gusts captured in our data), predicted canopy in developed urban areas decreased by 7.7%. Beyond the impacts of hurricanes and tropical storms, we found that historic landcover and two out of eight urban forest ordinances were significant predictors of existing canopy coverage (P-landcover <0.001; P-tree preservation ordinance = 0.02, P-heritage tree ordinance = 0.03). Results indicate that local policies and tree protections can protect or enhance urban tree canopy, even in the face of rapid development and periodic natural disturbances.

Agaricus blazei Murrill or Himematsutake is an edible and medicinal mushroom. Agaricus blazei Murrill's fruiting body extracts have anticancer properties, although the mechanism is unknown. Basic or organic solvents, which are hazardous for human health, are generally used to prepare Agaricus blazei Murrill's extracts. Inhibition of immune checkpoint molecules and Axl receptor is an effective therapy in cancer. This study assessed whether subcritical water extracts of the Agaricus blazei Murrill's fruiting body or mycelium affect the expression of Axl and immune checkpoint molecules in lung cancer cells. We used A549 cells and mouse bone marrow-derived dendritic cells in the experiments. We prepared subcritical water extracts from the Agaricus blazei Murrill's fruiting body or mycelium. The subcritical water extracts from the Agaricus blazei Murrill's fruiting body or mycelium significantly inhibited the expression of immune checkpoint molecules and Axl compared to saline-treated cells. Also, the hot water extract, subcritical water extract, and the hot water extraction residue subcritical water extract from the Agaricus blazei Murrill's mycelium significantly enhanced the expression of maturation markers in dendritic cells. These observations suggest that the subcritical water extract from Agaricus blazei Murrill's mycelium is a promising therapeutic tool for stimulating the immune response in cancer.

Often, engineers with machining experience often judge machining state and tool life according to chips’ features. Engineers' experience is digitized in this study. During the cutting process, the cutting tool coming in contact with the workpiece produces a shear zone, which causes plastic deformation and shear slip. The chips closest to the shear zone can directly show the state of the tool and workpiece when the material is SKD61. This study used chip color, vibration, and current signal integration for prediction of machining state and cutting tool life. When the cutting tool wears increased, the chip surface color changed in the following way: purpleè purple blueè blue ècyan, or even green and yellow. When the cutting tool was in the accelerating wear phase, the color change was particularly obvious. The Back-Propagation Levenberg–Marquardt (BP-LM) predictive methodology was used to compare the predictive ability of voltage, vibration signal, and chip color. The Mean Absolute Percentage Error (MAPE) for the voltage signal was 12.28%, for the vibration signal it was 11.38%, and for the chip color combined with multi-sensor characteristics it was 7.85%. The MAPE of the chip color was the smallest. Using the General Regression Neural Network (GRNN) methodology, the MAPE for the voltage signal was 10.74%, for the vibration signal 7.96%, and for the chip color combined with multi-sensor characteristics was 6.59%. The MAPE of the chip color was the smallest. Obviously, the chip color combined with multi-sensor signals provided better predictive results than the vibration signal or voltage signal alone. There is currently no research on the usefulness of monitoring chip color for tool life prediction.

Edge AI accelerators have been emerging as a solution for near customers’ applications in areas such as unmanned aerial vehicles (UAVs), image recognition sensors, wearable devices, robotics, and remote sensing satellites. These applications not only require meeting performance targets but also meeting strict reliability and resilience constraints due to operations in harsh and hostile environments. Numerous research articles have been proposed, but not all of these include full specifications. Most of these tend to compare their architecture with other existing CPUs, GPUs, or other reference research. This implies that the performance results of the articles are not comprehensive. Thus, this work lists the three key features in the specifications such as computation ability, power consumption, and the area size of prior art edge AI accelerators and the CGRA accelerators during the past few years to define and evaluate the low power ultra-small edge AI accelerators. We introduce the actual evaluation results showing the trend in edge AI accelerator design about key performance metrics to guide designers on the actual performance of existing edge AI accelerators’ capability and provide future design directions and trends for other applications with challenging constraints.

Due to the increasing global importance of decarbonizing human activities, especially the production of electricity, the optimal deployment of renewable energy technologies will play a crucial role in future energy systems. To accomplish this, particular attention must be accorded to the geospatial and temporal distribution of variable renewable energy sources (VRES) such as wind and solar radiation in order to match electricity supply and demand. This study presents a techno-economical assessment of four energy technologies in the hypothetical context of Mexico in 2050, namely: onshore and offshore wind turbines, and open-field and rooftop photovoltaics. A land eligibility analysis incorporating physical, environmental, and socio-political eligibility constraints and individual turbine and photovoltaic park simulations, drawing on 39 years of climate data, is performed for individual sites across the country in an effort to determine the installable potential and the associated levelized costs of electricity. The results reveal that up to 54 PWh of renewable electricity can be produced as a cost of less than 70 EUR/MWh. Around 91% (49 PWh) of this would originate from 23 TW of open-field photovoltaic parks that could occupy up to 578,000 km2 of eligible land across the country. The remaining 9% (4.8 PWh) could be produced by 1.9 TW of onshore wind installations allocated to approximately 68,500 km2 of eligible land that is almost fully adjacent to three mountainous zones. The combination of rooftop photovoltaic and offshore wind turbines account for a very small share of less than 0.03% of the overall techno-economical potential.

Background: this RCT assesses the 18 months clinical outcomes after regenerative therapy of periimplantitis lesions using either an electrolytic method (EC) to remove biofilms or a combination of powder spray and electrolytic method (PEC). Materials and Methods: Twenty-four patients (24 implants) suffering from periimplantitis were randomly treated by EC or PEC followed by augmentation and submerged healing. Probing pocket depth (PPD), Bleeding on Probing (BoP), suppuration and standardized radiographs were assessed before surgery (T0), 6 months after augmentation (T1), 6 (T2) and 12 (T3) months after replacement of the restoration. Results: Mean of PPD changed from 5.8 ± 1.6 mm (T0) to 3.1 ± 1.4 mm (T3). While BoP and suppuration at T0 was 100 % BoP decreased at T2 to 36.8 % and at T3 to 35.3 %. Suppuration could be found 10.6% at T2 and 11.8% at T3. Radiologic bone level measured from the implant shoulder to the first visible bone to implant contact was 4.9 ± 1.9 mm at me-sial and 4.4 ± 2.2 mm at distal sites (T0) and 1.7 ± 1.7 mm and 1.5 ± 17 mm at T3. Conclusions: Significant radiographic bone fill and improvement of clinical parameters were demonstrated 18 months after therapy.

(1) Background: Benefits and timing of percutaneous dilatational tracheostomy (PDT) in Intensive Care Unit (ICU) COVID-19 patients are still controversial. PDT is considered a high risk procedure for transmission of SARS CoV-2 to health care workers (HCWs). The present study analyzed optimal timing of PDT, clinical outcomes of patients undergoing PDT and safety of HCWs performing PDT. (2) Methods: 133 COVID-19 patients underwent PDT in our ICU from April 1, 2020 to March 31, 2021, 23 patients were excluded and 110 patients were enrolled. A trained medical team was dedicated to the PDT procedure. Demographic, clinical history and outcome data were collected. Patients who underwent PDT were stratified into two groups: early group, PDT ≤ 12 days from orotracheal-intubation (OTI) and late group, &gt;12 days from OTI; HCW surveillance program was performed. (3) Results: Early group included 57 patients and late group included 53 patients. Early group patients showed shorter ICU length of stay and fewer days of mechanical ventilation than the late group (p&lt;0.001). At day 7 after tracheostomy, early group patients required fewer intravenous anesthetic drugs and experienced an improvement of ventilation parameters, PaO2/FiO2-Ratio, PEEP and FiO2 (p&lt;0.001). No difference in case fatality ratio between the two groups was reported. No SARS-CoV-2 infection was reported in HCWs performing PDT. (4) Conclusions: PDT was safe and effective for COVID-19 patients, since it improved respiratory support parameters, reduced ICU length of stay and duration of mechanical ventilation, and optimized the weaning process. The procedure was safe for all HCWs involved in the dedicated medical team. The development of standardized early PDT protocols should be implemented and PDT procedure could be considered as first line approach in ICU COVID-19 requiring prolonged mechanical ventilation.

Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.

This article presents, for the first time, comprehensive model based on the proposed mechanism of Rahal et al [17], Bonardi {20], Tar et al [20], and Mau et al [24], for 3-component systems of G1/Iod/EDB, G1/Iod/amine (in gold chloride), and Iod/Benzoic/Borate (for reduced oxygen inhibition) for the hybri free radical (FRP) and cationic (CP) photopolymerization of interpenetrated polymer network (IPN) systems. Analytic formulas are developed to explore the new features including: (i) conversion efficacy(CE) of FRP is an increasing function of the light intensity (I), the effective absorption coefficient (b), for transient state, whereas, CE at steady-state is independent to the light intensity; (ii) initiator regeneration (RGE)
provides a catalytic cycle for improved CE for FRP and CP; (iii) in the IPN system, the synergic effects due to the co-exist of FRP and CP include: (i) CP can increase the medium viscosity limiting the diffusional oxygen replenishment, such that OIH is reduced; (ii) the cationic monomer also acts as a diluting agent for the radical polymer network, and (iii) the exothermic property of the CP polymerization. We have proposed ascaling law for the transient and steady-state dependence of CE on the key parameter P=bIC₀, given by a an m-order power law of P^m, with m = 0.5 to 1.5, depending on various conditions. The CE also has an optimal value for maximum CE. The presented comprehensive model (with minimum mathematics) focusing on the enhancement mechanisms/pathways, provides analytic formulas which can be used to analyze reported data, and, more importantly, serves as guidance for exploring new functional materials or new kinetic schemes for improved conversion or procedures for both industrial and medical applications such as additive manufacturing (AM), 3D and 4D bioprinting. Finally, we have proposed new directions/experiments based on our theoretical predictions.

It has been known that the performance of the High-Pressure Grinding Rolls (HPGR) varies as a function of method used to confine laterally the rolls, their diameter/length (aspect) ratio as well as their condition, if new or worn. However, quantifying these effects through direct experimentation in machines with reasonably large dimensions is not straightforward given the challenge, among others, of guaranteeing that the feed material remains unchanged. The present work couples the discrete element method (DEM) to multibody dynamics (MBD) and a novel particle replacement model (PRM) to simulate the performance of pilot-scale HPGRs grinding pellet feed. It shows that rotating side plates, in particular when fitted with studs, allow reaching more uniform forces along the bed, which also translates in a more constant product size along the rolls as well as higher throughput. It also shows that the edge effect is relatively constant with roll length, leading to substantially larger proportional edge regions for high-aspect ratio rolls. On the other hand, the product from the center region of such rolls was found to be finer when pressed at identical specific forces. Finally, rolls were found to have higher throughput, but generate a coarser product when worn following the commonly observed trapezoidal profile. The approach used in industry to compensate for roller wear by increasing the specific force and roll speed has then been demonstrated to be effective to maintain and potentially even increase product fineness and throughput, as long as the minimum safety gap is not reached.

Atopic dermatitis (AD) is common inflammatory dermatosis, typically with chronic and recurrent course, which significantly reduces the quality of life. Sleep disturbances are considered to be remarkably burdensome ailments in the patients with AD, and are routinely included during assessment of disease severity. Therefore, endogenous substances engaged in the control of circadian rhythms might be important in pathogenesis of AD and, possibly, be used as biomarkers of disease severity or even in development of novel therapies. Melatonin (MT), the indoleamine produced by pineal gland (but also by multiple other tissues, including skin), plays a pivotal role in maintaining the sleep/wake homeostasis. Additionally, it possess strong antioxidant and anti-inflammatory properties, which might directly link chronic skin inflammation and sleep abnormalities characteristic of AD. The objective of this work is to systematically present and summarize the results of studies (both experimental and clinical) that investigated the role of MT in the AD, with focus on the antioxidant and immunomodulatory effects of MT.

Objectives: To explore the potential of Radiomics alone and in combination with diffusion-weighted derived quantitative parameter namely apparent diffusion co-efficient (ADC) using supervised classification algorithms in predicting outcomes and prognosis. Materials and Methods: Retrospective evaluation of the imaging was done for a study cohort of uterine cervical cancer, candidates for radical treatment with chemo radiation. ADC values were calculated from the darkest part of the tumor, both before (labeled preADC) and post treatment (labeled postADC) with chemo radiation. Post extraction of 851 Radiomics features and feature selection by taking the union of the features which had Pearson correlation >0.35 for recurrence, >0.49 for lymph node and >0.40 for metastasis, analysis was done to predict clinical outcomes. Results: The study enrolled 52 patients who presented with variable FIGO stages and age range 28–79 (Median = 53 years) with median follow-up of 26.5 months (range, 7–76 months). Disease recurrence occurred in 12 patients (23%). Metastasis occurred in 15 patients (28%). A model generated with 24 radiomics features and preADC using a monotone multi-layer perceptron neural network to predict the recurrence yields AUC of 0.80 and kappa value as 0.55 and shows that addition of radiomics features on ADC values improves the statistical metrics by 40% approximately for AUC and 223% approximately for Kappa. Similarly, neural network model for prediction of metastasis re-turns AUC of 0.84 and kappa value as 0.65 over performs by 25% for AUC and 140% for Kappa approximately. There was a significant input of GLSZM features (SALGLE and LGLZE) and GLDM features (SDLGLE and DE) correlation with clinical outcomes of recurrence and metastasis. Conclusions: The study is an effort to bridge the unmet need of translational predictive biomarkers in stratification of uterine cervical cancer patients based on prognosis.

This dissertation presents a method for the synthesis of substituted indoles bearing heterocyclic substituents onto the 3- position. The route for the synthesis of the heterocyclic substituents indoles starts from 3-acetyl indole nucleus depend on two parts. One part: Reaction of 3-acetylindole 1 with hydrazide compounds such as phenyl hydrazine, hydrazine hydrate, and thio-semicarbazide, to yield 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2, 3-(1-hydrazonoethyl)-1H-indole 6, and thiosemicarbazone 10 respectively. 3-(1-Hydrazonoethyl)-1H-indole 6 reacted with thiophene-2-carboxaldeyde, isatin and 3-acetyl indole. In the same way, 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2 reacted with thioglycollic acid, glycine and benzaldehyde. 3-Acetylindole 1 thiosemicarbazone reacted with acetic anhydride, piperidine, concentration of hydrochloric acid and thiophene-2-carboxaldeyde. Second part. Reaction of 3-acetyl indole 1 with amines compounds such as p-nitroaniline to formed Schiff base 15 which it reacted with thioglycollic acid to give compound 16. 3-Acetyl indole 1 reacted with ethylene diamine to afford bis imine indole to afford compound 17. The reports of this docking study revealed that the new compounds exhibit good antibacterial activity. The synthesized compounds screened in vitro for their antibacterial activity revealed remarkable inhibitory effects against the selected microorganisms. And also an anti-oxidant activity studying for some synthesized compounds. Structures of the newly synthesized compounds examination by spectral data (IR, 1H- NMR and 13C -NMR).

The Benford method can be used to detect manipulation of epidemiological or trial data during the validation of new drugs. We extend here the Benford method after having detected particular properties for the Fibonacci values 1, 2, 3, 5 and 8 of the first decimal of 10 runs of official epidemiological data published in France and Italy (positive cases, intensive care, and deaths) for the periods of March 1 to May 30, 2020 and 2021, each with 91 raw data. This new method – called “BFP” for Benford-Fibonacci-Perez - is positive in all 10 cases (i.e. 910 values) with an average of favorable cases close to 80%, which, in our opinion, would validate the reliability of these basic data.

Introduction: The imbalance between technological development and ideological strengthening has resulted in the fading of the Pancasila ideological values of millennials. Technology that accompanies everyday life seems to be the main character in human life. Yet if humans themselves do not use technology wisely, technology can be a threat to both individuals and the life of the nation and state. If technology is increasingly out of control, threats to the Pancasila ideology are very likely to occur, such as in the G 30S PKI incident. Therefore, it is necessary to take action both from the government and the community as individuals to safeguard the development of technology to be used wisely. That way, we can prevent the threat to the Pancasila ideology together. Writing this article aims to analyze how the role and influence of the Pancasila ideology on the millennial generation in the 4.0 industrial revolution and to find solutions so that the values of Pancasila remain attached to the next generation of the Indonesian nation. Method: Writing This article uses a qualitative method by using literature reviews from the results of related research journals that have been published online through websites and other online media. Results: Thirteen journals and one book have met the criteria for the inclusion of a predetermined review. Research is based on the stigma of society regarding technological developments in the Industrial revolution 4.0. Therefore, the government is expected to be more severe in implementing human capital management. Conclusion: By procuring human capital management, it will be possible that Human Resources (HR) in Indonesia will be able to carry out the ideals of a golden Indonesian generation with Pancasila values inherent in the hearts of the people and the nation's future generations.

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

The present study was conducted the status of sea bass from Kokko and Kyuntone of The Gulf of Motttama Wetland (GoMW) area in Thanatpin Township in Bago Region Myanmar from September 2019 to August 2020. Fifty specimens were monthly collected, measured and weighed. Invoices of sea bass were collected for the depot and fish sellers by monthly. In Kokko, mean value of standard length and body weight were highest in March (32.70±1.58, 660.7±112.23). The mean value of standard length was peak in January (31.39±7.16) but peak of body weight was in March (963.24±280.86) in Kyuntone villages. The lowest mean value of standard length and body weight were found in June at both study areas. According to the invoice data revealed that monthly catch weight of sea bass is most abundance in October (829.92) kg in Kokko, (339.12) kg in Kyuntone. Based on price of relations to size group, small size C &lt; 300g (41%) was mostly abundance in Kokko and in Kyuntone small size C &lt; 300g (35%) was second abundance. Specimens were not landed in April and May. In June, young specimens were very rarely seen in both study sites. The important roles of wetland fishes, the economic valuation of GOMW in Myanmar and samples of fishing gear and value chain of sea bass in Myanmar was expressed in this study.

In this paper, the author utilizes Saddle Theorem and variational methods to deduce existence of at least six stationary solutions for reaction-diffusion Gilpin-Ayala competition model (RDGACM). To obtain the global stabilization of the positive stationary solution of the RDGACM, the author designs a suitable impulsive event triggered mechanism (IETM) to derive the global exponential stability of the the positive stationary solution. It is worth mentioning that the new mechanism can exclude Zeno behavior and effectively reduce the cost of impulse control through event triggering mechanism. Besides, compared with existing literature, the restrictions on the parameters of the RDGACM are relaxed so that the methods used in existing literature can not be applied to the relaxed case of this paper, and so the author makes comprehensive use of Saddle Theorem, orthogonal decomposition of Sobolev space $H_0^1(\Omega)$ and variational methods to overcome the mathematical difficulty. Numerical examples show the effectiveness of the methods proposed in this paper.

Capirona (Calycophyllum spruceanum Benth) is a tree species of commercial importance widely distributed in South American forests and is traditionally used for its medicinal properties and wood quality. Studies on this tree species have been focused mainly on wood properties, propagation and growth. Genetic studies on capirona are very limited to date. Today it is possible to explore genetic diversity and population structure in a fast and reliable manner by using molecular markers. We here used 10 Random Amplified Polymorphic DNAs (RAPDs) markers to analyze genetic diversity and population structure of 59 samples of capirona that were sampled from four provinces located in the eastern region of the Peruvian amazon. A total of 186 bands were manually scored, generating a 59 x 186 presence/absence matrix. We used R software to calculate genetic distances based on provesti coefficient. A dendrogram was generated using the UPGMA clustering algorithm and showed four groups that correspond to the geographic origin of the capirona samples. Similarly, a discriminant analysis of principal components (DAPC) confirmed that capirona is grouped into four clusters. However, we also noticed few accessions are intermingled. Genetic diversity estimation was conducted considering the four groups (populations) identified by adegenet package in R. Nei's genetic diversity estimate varied from 0.26 to 0.39 and Shannon index ranged from 2.48 to 2.83. AMOVA analysis revealed the greatest variation exist within populations (69.7%) and indicated that variability among populations is 31.5%. To our best knowledge, this is the first investigation employing molecular markers in capirona in Peru considering their natural distribution, and sheds light towards its modern genetic improvement and for the sustainable management of forests in Peru.

Colorectal cancer prognosis get worse with advancement of disease into metastatic stage. There is a pertinent need to develop prognostic biomarkers that can be used for personalized and precision medicine. Alternative splicing provides an insight into understanding of changes at isoform expression level which may not be evident at gene level. In this direction, we utilized our prior knowledge about significant alternatively spliced genes and chose ADAM12 and MUC4 for further characterization in a metastatic cell line model. These genes were found to be good prognostic indicators in The Cancer Genome Atlas database. We studied the gene organization and designed primers to specifically amplify a group of isoforms. Differential expression of these group of isoforms was observed in normal, primary and metastatic colorectal cancer cell lines. We further validated the results using sanger sequencing. Isoform expression was found to respond to the 5-fluorouracil treatment. RNAseq analysis of the cell lines further validated the differential expression of gene isoforms. Successful detection of ADAM12 and MUC4 in cell lysates varied according to the antibody used which may reflect differential expression of isoforms. This comprehensive study underscores the importance of studying alternatively spliced isoforms and their probable used as prognostic or predictive biomarkers.

The current paper aims to contribute to the literature on community renewable energy by considering two projects developed in the north-west of Italy, in the Piedmont region. The case-studies are analysed by combining two theoretical perspectives: the multilevel perspective and the sociotechnical imaginary approach. On the one hand, applying the first perspective helps reconstruct the context and circumstances that have permitted Piedmont’s energy community projects to emerge. In particular, attention is given to the windows of opportunity created by the passing of the Milleproroghe decree at the national level and by the ensuing regional law 12/2018, which acknowledged the establishment of energy communities in the Piedmont. On the other hand, the sociotechnical imaginary approach allows identifying collective ideas and meanings that emerge when individuals or groups promote a sociotechnical innovation. In our cases, two main future changes are associated with community renewable energy: an integral ecology approach and a stronger sense of community on the one hand, and local development opportunities for rural areas characterised by depopulation, low employment rate and high energy demand, on the other.

Testing and isolation have been crucial for controlling the COVID-19 pandemic. Venezuela has one of the weakest testing infrastructures in Latin America and the low number of reported cases in the country has been attributed to substantial underreporting. However, the Venezuelan epidemic seems to have lagged behind other countries in the region, with most cases occurring within the capital region and four border states. Here, we describe the spatial epidemiology of COVID-19 in Venezuela and its relation to population mobility, migration patterns, non-pharmaceutical interventions and fuel availability. Using an SEI metapopulation model, we explore how movement patterns could have driven the observed distribution of cases. Low within-country connectivity most likely delayed the epidemic in most states, except for those bordering Colombia and Brazil where high immigration seeded outbreaks. NPIs slowed early epidemic growth and subsequent fuel shortages appeared to be responsible for limiting the spread of COVID-19 across the country.

The purpose of this study was to investigate the relationships among student athlete’s identity and mental health during the COVID-19 pandemic. In addition, this study aimed to clarify the relationship between perceived social support from teammates and mental health in student-athletes. Two studies were conducted to investigate to clarify the mental health states of student-athletes in Japan during the COVID-19 pandemic. In Study 1 conducted in April 2020, the participants were 402 male student-athletes, and examined the relationships among student-athlete’s identity and mental health. The results of correlational analyses indicated that there were significant negative correlations between degree of student-athlete’s identity and depression and sports helplessness. In Study 2 conducted in March 2021, the participants were 136 male student-athletes, and examined the relationship between perceived social support from teammates, student-athlete’s identity and mental health. The results indicated that there was significant correlation among social support, student athlete’s identity and mental health. These results suggested that mental health may be improved if student-athletes are strongly aware of their social identity, which is their social role, when unforeseen events such as the COVID-19 pandemic occur. In addition, social support provided by significant others such as teammates may contribute to the improvement of mental health.

An accurate understanding of jointed rock mass behavior is important in many applications ranging from deep geological disposal of nuclear waste to deep mining to urban geoengineering projects. The roughness of rock fractures and the matching of the fracture surfaces are the key contributors to the shear strength of rock fractures. In this research, push shear tests with three normal stress levels of 3.6, 6.0, and 8.5 kPa were conducted with two granite samples with artificially induced well-matching tensile fractures with sizes of 500 mm × 250 mm and 1000 mm × 500 mm. The large sample reached on average a -60 % weaker peak shear stress than the medium-sized sample, and a strong negative scale effect was observed in the peak shear strength. The roughness of the surfaces was measured using a profilometer and photogrammetry. The scale-corrected profilometer-based method (JRC) underestimates the peak friction angle for the medium-sized slabs by -27 % for the medium sample and -9 % for the large sample. The photogrammetry-based (Z’2) method produces an estimate with -7% (medium) and +12 % (large) errors. The photogrammetry-based Z’2 is an objective method that consistently produces usable estimates for the JRC and peak friction angle.

Septic shock substantially alters the pharmacokinetic properties of ß-lactams with a subsequently high risk of insufficiently low serum concentrations and treatment failure. Considering their pharmacokinetic (PK)/pharmacodynamic (PD) index, prolonged infusions (PI) of ß-lactams extend the time that the unbound fraction of the drug remains above the minimal inhibitory concentration MIC (ft >MIC) and may improve patient survival. The present study is a monocentric, retrospective before-and-after analysis of septic shock patients treated with ß-lactams. Patients of the years 2015-2017 received intermittent bolus application whereas patients of 2017-2020 received PI of ß-lactams. The primary outcome was mortality at day 30 and 90 after diagnosis of septic shock. Mortality rates in the PI group were significantly lower on day 30 (PI: 41%, n=119/290 vs. IB: 54.8%, n=68/114; p=0.0097) and day 90 (PI: 47.9%, n=139/290 vs. IB: 62.9%, n=78/124; p=0.005). After propensity-score matching, 30- and 90-day mortality remained lower for the PI group (-10%). PI further reduced duration of invasive ventilation. PI of β-lactam antibiotics led to a stronger decrease in SOFA scores within a 14d-observation period. PI of ß-lactams significantly reduces mortality in patients with septic shock and may have beneficial effects on invasive ventilation and recovery from sepsis-related organ failure.

This paper discusses the tectonics of the St. Peter and St. Paul Archipelago (SPSPA) in the Equato-rial Atlantic Ocean, based on the joint-system geometry which show a North-South shorten-ing/transpressional uplift tectonism, is active leading to exhumation of the sub-oceanic mantle. These islets are the summits of a sigmoidal submarine ridge formed by mantle ultramafic rocks. The ridge is crossed by the principal transform deformation zone of the northern transform fault of the St. Paul Multifault System. The South flank ridge exposes serpentinized mantle perido-tites, while the North flank exposes strongly deformed/fractured ultramylonites, recording duc-tile and brittle deformation at lithospheric conditions. The SPSPA show multiple joint systems cutting mylonitic foliation of the exposed rocks, forming three main families: high-angle paral-lel joints of tectonic origin, serpentinization-related joints with random direction and load-release low-angle parallel joints. The tectonic joints show an average direction of N31°E and N28°W, forming a conjugate system with a N1ºW compression axes, coherent with a trans-pressive stress field. Accordingly, the earthquakes focal mechanism close to the islets also shows N-S compression. The previously reported active uplift with an average rate of 1.5 mm/year and the directions of the joint system here reported agreeing with a present-day active N-S compres-sive field at a high angle with the direction of the transform fault.

One of the most significant developments in the sports world over the last two decades has been the use of mathematical methods in conjunction with the massive amounts of data now available to analyze performances, identify trends and patterns, and forecast results. Football analytics has advanced significantly in recent years and continues to evolve as it becomes a more recognized and integral part of the game. Football analytics is also used to forecast game outcomes, allowing bettors to make educated guesses. This article describes mathematical concepts related to football analytics that enable a better betting strategies. We explain how the pitch is partitioned into different zones and we define possession sequences. Furthermore, we explain what an expected goals model is and which expected goals model we use in this research. Furthermore, we define two general characteristics of a player evaluation method, each corresponding to one of the equations of the Dawson model. Based on these characteristics, we describe the developments of several general approaches for evaluating players in the context of the Dawson model.

Background: General Practitioners (GP) have an important role in the prevention of suicidal behavior. The purpose of this study was to explore their views and experiences of identifying and assessing suicidal ideation. Methods: Ten GPs were recruited through convenience sampling, based on accessibility, interest and willingness to participate. In-depth interviews were carried out and results transcribed ver-batim. Aspects of experiences with suicidal patients emerged through the thematic analyses process. Results: The GPs described the varied clinical picture when patients presented in their office. How they identified depressive symptoms apart from originally somatic complaints, formed a trusting relationship and addressed suicide ideation. They described customized interventions as well as obstacles and factors that facilitated communication: time, own personal traits, pa-tient’s disclosure and organizational barriers. Conclusions: The levels of the suicidal process among patients in general practice vary greatly. GPs adjust their appraisals to profundity understand and intervene in order to prevent a crisis to escalate into subsequent suicidal behavior.

Competition over environmental and natural resources characteristically lies at the heart of armed conflicts in Africa. It is also common knowledge that some companies dealing in products such as laptops, smart phones and jewellery; import minerals from conflict-affected areas, thereby indirectly fuelling conflicts in these areas or undermining human rights. For a continent endowed with natural resources including minerals, Africa has suffered the brunt of this predicament. This state of affairs has lent impetus to the adoption of several regulations geared towards curbing irresponsible business practices by companies relying on such minerals, the goal being, amongst others, to guarantee the protection of human rights. In May 2017, the European Union adopted Regulations intended to stop the importation of conflict minerals in Europe, debatably making giant strides in the direction of protection of human rights. These Regulations are to come into force in 2021. However, can these regulations advance the much-desired goal of protection of human rights in Africa on issues pertaining to conflict minerals? By analyzing the 2017 EU Regulations in light of previous regulations of a similar nature, the paper concludes that the said regulations constitute a weak normative framework and could in fact have unintended consequences on the fundamental rights of civilians in natural resource-rich conflict areas of Africa.

Climate change has emerged as one of the defining issues of the early 21st century. It is now more certain than ever and poses a serious threat to sustainable urban development. Climate change has many destructive effects on cities. Land subsidence, rising air pollutants, severe storms, dust and water scarcity are just some effects of this phenomenon in the urban area of ​​Tehran. Urban management must be prepared to deal with these effects and adopt policies to mitigate and adapt to climate change. One of these tools in urban planning is urban development plans. The plans can have a great impact on controlling and counteracting with the effects of climate change. In this research, using content analysis method, 6 dimensions and 31 indicators have been used to evaluate 8 city and region development plans of Tehran from the view of reflecting the effects of climate change. Indicators were scored after studying the content of the plans. Findings indicate that among the reviewed plans, the second and third five-year development plans of Tehran with 61.9% and 61.3% as the highest rate and plan to reduce air pollution in Tehran and the transportation master plan with 20.6% and 23.2%, respectively have the least attention to the effects of climate change. Also, among the indicators, the urban transportation sector with 54.3% as the highest and the energy sector with 20.5% have the least attention to mitigation and adaptation policies.

High temperature (HT) significantly affects the crop physiological traits and reduces the 12 productivity in plants. To increase yields as well as survival of crops under HT, developing heat13 tolerant plants is one of the main targets in crop breeding programs. The present study attempted 14 to investigate the linkage of the heat tolerance between the seedling and the reproductive growth 15 stages of tomato cultivars ’Dafnis‘ and ’Minichal’. This research was undertaken to evaluate heat 16 tolerance under two experimental designs such as screening at seedling stage and screening from 17 reproductive traits in greenhouses. Survival rate and physiological responses in seedlings of 18 tomatoes with 4-5 true leaf were estimated under HT (40 °C, RH 70%, day/night, respectively) and 19 under two control and HT greenhouse conditions (day time 28 °C and 40 °C, respectively). Heat 20 stress significantly affected physiological-chemical (photosynthesis, electrolyte conductivity, 21 proline) and vegetative parameters (plant height, shoot fresh weight, root fresh weight) in all 22 tomatoes seedlings. The finding revealed that regardless of tomato cultivars the photosynthesis, 23 chlorophyll, total proline and electrical conductivity parameters were varied in seedlings during the 24 heat stress period. The heat tolerance rate of tomatoes in the seedling stage might not be associated 25 always with reproductive parameters. HT reduced the fruit parameters likeas fruit weight (31.9%), 26 fruit length (14.1%), fruit diameter (19.1%) and fruit hardness (9.1%) in compared to NT under HT 27 in heat susceptible tomato cultivar ‘Dafnis’, while in heat tolerant cultivar ‘Minichal’ fruit length 28 (7.1%) and fruit diameter (12.1%) was decreased by the affect of HT but on the contrary fruit weight 29 (3.6%) and fruit hardness (8.3%) were increased. In conclusion, screening and selection for tomatoes 30 should be evaluated at the vegetative and reproductive stages with consideration of reproductive 31 parameters.

Although carbon (C) efflux from soils treated with organic wastes was widely covered in temperate and cold regions, still such data is not sufficient from arid and semi-arid regions. Saudi Arabia produces more than 335,000 tons/year of cow manure (CM), this CM either left as raw manure or being composted. The application of high C/N amendments is expected to increase soil organic carbon and reduce CO₂ fluxes. A 90-day incubation experiment was conducted to study CO₂ efflux, organic C microbial biomass C, available NH₄+and NO₃-when added to agricultural soil. Six manure types were added: cow manure, cow manure compost, cow manure biochar, cow manure stripped ammonia at pH 12 with a temperature of 95oC, cow manure stripped ammonia at pH 9 with a temperature of 95oC and control. The application of CM resulted in a considerable increase in soil available nitrogen, CO₂ efflux compared to other treatments. Cow manure biochar showed the lowest CO₂ efflux. Cumulative CO₂ effluxes of cow manure effluents were lower than CM this possibly due to the relatively high C:N ratio of manure effluent. The content of, P, Fe, Cu, Zn and Mn were decreased as incubation time increased. microbial biomass C of cow manure stripped ammonia at pH 12 with a temperature of 95oC were increased at 7 and 60 days illustrating to temperature effect on the decomposing of manure materials.

Cholinergic innervation in pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The pharmacological ACh concentration further increases the oscillation frequency on the level of individual beta cells, inhibits the synchronization between these cells, and abolishes oscillatory activity in acinar cells. We discuss possible mechanisms leading to the observed phenomena.

Chikungunya is a mosquito-borne viral disease caused by Chikungunya virus (CHIKV. We conducted this study determine the seroprevalence and clinical presentation of Chikungunya infection among outpatients seeking healthcare in Mzuzu City, Malawi. Blood samples were collected from malaria negative and non-septic febrile outpatients with fevers ≥38 °C, for not more than 5 days. The enzyme- linked immunosorbent assay (ELISA) test was used to detect anti-CHIKV IgM antibodies and its results were used to determine seroprevalence of Chikungunya. A total of 119 serum samples were tested, of these, 73 (61.3%) tested positive for anti-CHIKV IgM antibodies by ELISA. Laboratory requisition forms were used to capture demographic information such as age, sex, clinical signs and symptoms presented by the enrolled patients. Age groups of 1-9, 10- 19, 20- 29, 30- 39, 40- 49, and ≥50 years had 17.8% (n= 13), 12.3 %,( n=9), 15.1%) (n=11), 19.2%; (n=14), 17.8% (n=13) and 17.8% (n=13) proportion of seroprevalence respectively. Most of the CHIKV infected individuals presented with fever (52.05%), joint pain (45.21%) and abdominal pain (42.67%). The presence of anti- CHIKV IgM antibodies suggest the presence of recent CHIKV infection and therefore accurate laboratory assays are highly recommended for CHIKV diagnosis and appropriate management of febrile patients.

Fusarium head blight (FHB) can cause contamination of cereal grain with mycotoxins. Winter wheat is also infected with FHB. It is more resistant than durum wheat to head infection and less than other small grain cereals. The aim of this study was to identify winter wheat lines that combine low head infection and kernel damage with low toxin contamination. Resistance to FHB of 27 winter wheat lines and cultivars was evaluated over a three-year experiment established in two locations. At the anthesis stage, heads were inoculated with Fusarium culmorum isolates. The FHB index was scored and the percentage of Fusarium-damaged kernels (FDKs) assessed. The grain was analysed for type B trichothecenes (deoxynivalenol and derivatives, nivalenol) and zearalenone content. The average FHB index was 12.9%. The proportion of FDK was 6.9% (weight) and 8.5% (number). An average content of deoxynivalenol amounted to 3.543 mg/kg and nivalenol to 2.115 mg/kg. In total, it was 5.804 m/kg of type B trichothecenes. The zearalenone content in the grain was 0.214 mg/kg. Relationships between FHB index, FDK and mycotoxin contents were highly significant for wheat lines; however, they were stronger for FDK versus mycotoxins. Breeding lines combing all types of FHB resistance were found, and five of them had resistance similar to that of wheat lines with the Fhb1 gene.

This article addresses the generic dynamic decision problem of how to achieve sustained market growth by increasing two interdependent organizational resources needed (1) to increase and (2) to sustain demand. The speed and costs of increasing each resource are different. Failure to account for this difference has been reported to lead to policies that drive a quick increase of demand followed by decline. Three generic policies derived from the literature have been implemented in a system dynamics model. Simulation shows that all three policies can generate sustained exponential growth but differ in performance. These results suggest that even policies which risk generating overshoot and collapse can avoid it. This poses two questions for further research: (1) what is the reasoning of human decision-makers when choosing between these policies and (2) how can the important but easily overlooked features of such decision situations be made sufficiently salient to be accounted for?

High-strength low-alloy steels (HSLAs) are widely used in the structural body components of many domestic motor vehicles owing to their better mechanical properties and greater resistance. The real production process of HSLA steelmaking can be regarded as a model that builds on the relationship between process parameters and product quality attributes. A surrogate modeling method is used, and the resulting production process model can be applied to predict the optimal manufacturing process parameters. We used different methods in this paper to build such a surrogate model, including linear regression, random forests, support vector regression, multilayer perception, and a simplified VGG model. We then applied three bio-inspired search algorithms, namely particle swarm optimization, the artificial bee colony algorithm, and the firefly algorithm, to search for the optimal controllable manufacturing process parameters. Through experiments on 9,000 test samples used for building the surrogate model, and 299 test samples for making the optimal process parameter selection, we found that the combination of a simplified VGG model and the firefly algorithm was the most successful at reaching a success rate of 100%—in other words, when the product quality attributes of all test samples satisfy the mechanical requirements of the end products.

Although CAD/CAM ceramics present a promising alternative to metal-ceramic fixed dental prostheses, little is known about their mid- and long-term clinical performance. This systematic review aims to estimate the survival and success rates and describes the underlying complication characteristics for CAD/CAM tooth-supported fixed dental prostheses (FDPs). We systematically searched MEDLINE and Web of Science to find relevant prospective studies with a follow-up of at least one year. We estimated pooled 1-, 5- and 10-year survival and success rates by combining the collected data in a Poisson regression model. Descriptive statistics were conducted to evaluate the distribution of failures and complications in the included studies. Risk of bias for the included studies was assessed with an adapted checklist for single-arm trials. Pooled estimated 1-, 5-, and 10-year survival rates ranged from 93.80% to 94.66%, 89.67% to 91.1%, and 79.33% to 82.20%, respectively. The corresponding success rates, excluding failures but including any other types of intervention, were 94.53% to 96.77%, 90.89% to 94.62%, and 81.78% to 89.25%. Secondary caries was the most frequent cause of failure, followed by chipping of the veneering. The most common cause of complication, excluding failures but requiring intervention, was chipping of the veneering. Risk of bias was generally acceptable for the included studies, with 7 studies associated with low risk of bias, 8 studies with a moderate risk of bias, and 3 studies with serious risk of bias. The current meta-analysis on CAD/CAM supported FDPs revealed satisfying survival and success rates for up to 10 years of exposure. More prospective studies focusing on long-term performance are needed to strengthen the evidence currently available in the literature.

Background: Colorectal cancer is considered the third most fetal among all type of cancer. Spleen tyrosine kinase (SYK) is a non-receptor type tyrosine-protein that plays crucial role in signaling mediated via immune receptor. We adopted an onco-informatics analysis to evaluate the SYK expression and prognostic value of SYK in colorectal cancer, and identification of potential phytochemicals which may inhibit overexpression of SYK protein as well as minimized colorectal cancer. Materials & Methods: Differential expression of SYK gene was analyzed using the several transcriptomic databases including Oncomine, UALCAN, GENT2 and GEPIA2. The server, cBioPortal was used to analyze mutation and copy number alterations whereas GENT2, GEPIA, OncoLnc and PrognoScan were employed to examine the survival rate. A protein-protein interaction network of SYK and co-expressed genes of SYK was conducted via GeneMANIA. Considering SYK gene encoding protein as drug target, selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. YASARA molecular dynamics simulators were applied for the post validation of the molecular docking data. Results: We have observed significant overexpression of mRNA expression levels of SYK gene colorectal adenocarcinoma (COAD) samples compared with normal tissues. Significant methylation level and various genetic alterations are assembled in SYK gene which can lead to the development of colorectal cancer. As a result, lower level of SYK expression was related to the more chances of patients’ survival by which all the outcomes from the multiple bioinformatics platforms and web resources have demonstrated the significant evidences that the SYK kinsase can possess as a potential biomarker for the treatment of colorectal cancer. Here, aromatic phytochemicals namely, Kaempferol and Glabridin targeting SYK showed more stability compared to controls and may be useful for the treatment of colorectal cancer. Conclusion: Our study showed dysregulated expression of SYK in colorectal cancer and potentiality to act as a biomarker for the prognosis of CRC. Moreover, we have shown phytochemicals (Kaempferol and Glabridin) target SYK as potential treatment strategies and drug repositioning potentiality in colorectal cancer.

The risk of inhalation exposure to elevated concentrations of hydrogen sulfide (H₂S) and ammonia (NH₃) during the agitation of stored swine manure is high. Once or twice a year, farmers agitate manure before pump-out and application to fields. Agitation of the swine manure causes the short-term releases of highly toxic levels of H₂S and NH₃. In our previous pilot-scale studies, the biochar powder had shown significant mitigation of H₂S and NH₃ emissions when surficially applied to manure immediately before agitation. However, fine biochar powder application poses hazards by itself and may not be practical to apply on a farm scale, especially when livestock and workers are present. We hypothesized that applying pelletized biochar to manure surface is just as effective as applying powder to protect farmers and animals from excessive exposure to H₂S and NH₃. This work reports on the lab-scale proof-of-the-concept trials with biochar pellets on the lab-scale. The objective was to compare the biochar pellets and biochar powder on their effectiveness of mitigation on H₂S and NH₃ gases during 3-hour long swine manure agitation. Three scenarios were compared in (n=3) trials (i) control, (ii) 12.5 mm thick surficial application to manure surface of biochar powder, and (iii) an equivalent (by mass) dose of pelletized biochar applied to manure surface. The biochar powder was bound with 35% (wt) water into ~5 × 10 mm (dia × length) pellets. Biochar powder was significantly (p<0.05) more effective than the biochar pellets. Still, pellets reduced total H₂S and NH₃ emissions by ~72% and ~68%, respectively (p=0.001), compared with ~99% by powder (p=0.001). The maximum H₂S & NH₃ concentrations were reduced from 48.1±4.8 ppm & 1,810±850 ppm to 20.8±2.95 ppm & 775±182 ppm by pellets, and to 22.1±16.9 ppm & 40.3±57 ppm by powder, respectively. These reductions are equivalent to reducing the maximum concentrations of H₂S and NH₃ during the 3-h manure agitation by 57% and 57% (pellets) and 54% and 98% (powder), respectively. Treated manure properties hinted at improved nitrogen retention, yet not significant due to high variability. We recommend scaling-up and trials on the farm-scales using biochar pellets to assess the feasibility of application to large manure surfaces and techno-economic evaluation.

The COVID-19 pandemic has put lifestyles in question, changed daily routines and limited citizen freedoms that seemed inalienable before. A human activity that was greatly affected since the beginning of the health crisis is mobility. Focusing on mobility, we aim to discuss the transformational impact that the pandemic brought on this specific urban domain, especially with regards to the promotion of the smart growth agenda and the acceleration towards the smart city paradigm. We collect 60 initial policy responses related to urban mobility from 86 cities around the world and analyse them based on the challenge they aim to address, the exact principles of smart growth and sustainable mobility that they encapsulate and the level of ICT penetration. Our findings suggest that emerging strategies, although mainly temporary, are transformational, in line with the principles of smart growth. As a result the pandemic becomes an opportunity for shifting towards more sustainable urban planning and mobility practices. However, most policy responses adopted during the first months of the pandemic fail to leverage advancements made in the field of smart cities, and to adopt off-the-shelf solutions such as in monitoring, alerting and operations management.

This study explores the use of satellite-based LULC (Land Use / Land Cover) data while simultaneously correcting potential evapotranspiration (PET) input with Leaf Area Index (LAI) to increase the performance of a physically distributed hydrologic model. The mesoscale hydrologic model (mHM) was selected for this purpose due to its unique features. Since LAI input informs the model about vegetation dynamics, we incorporated the LAI based PET correction option together with multi-year LULC data. The Globcover land cover data was selected for the single land cover cases, and hybrid of CORINE (coordination of information on the environment) and MODIS (Moderate Resolution Imaging Spectroradiometer) land cover datasets were chosen for the cases with multiple land cover datasets. These two datasets complement each other since MODIS has no separate forest class but more frequent (yearly) observations than CORINE. Calibration period spans from 1990 to 2006 and corresponding NSE (Nash-Sutcliffe Efficiency) values varies between 0.23 and 0.42, while the validation period spans from 2007 to 2010 and corresponding NSE values are between 0.13 and 0.39. The results revealed that the best performance is obtained when multiple land cover datasets are provided to the model and LAI data is used to correct PET, instead of default aspect-based PET correction in mHM. This study suggests that to minimize errors due to parameter uncertainties in physically distributed hydrologic models, adequate information can be supplied to the model with care taken to avoid over-parameterizing the model.

(1) Background: Stimulating oropharyngeal transient receptor potential (TRP) channels inhibits muscle cramping by triggering a supraspinal reflex to reduce α-motor neuron hyperexcitability. This study investigated whether longer stimulation of TRP channels via mouth rinsing with PJ is more effective than drinking PJ at inhibiting an electrically induced muscle cramp (EIMC); (2) Methods: Tibial nerve in 11 cramp-prone adults were percutaneously stimulated to elicit an EIMC of flexor hallucis brevis in three trials 1-week apart. At cramp onset participants received mouth rinsing and expelling PJ (25 mL), ingesting PJ (1 mL∙kg-1 body-mass [BM]), or ingesting water (1 mL∙kg-1 BM). Cramp onset and offset by electromyography and severity of discomfort was recorded using a visual analogue scale (VAS); (3) Results: Median time to cramp cessation as a percentage of water was 82.8% ± 14.634 and 68.6% ± 47.782 for PJ ingestion and mouth rinse respectively. These results had large variability and no statistically significant difference was observed. There were also no differences in perceived cramp discomfort between conditions, despite hazard ratios for time to VAS = 0 higher than water for PJ ingestion (22%) and mouth rinse (35%) (p = 0.66 and 0.51 respectively); (4) Conclusions: Data suggest no difference in cramp duration and perceived discomfort between PJ and water.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

This article presents and discusses analytical data on the scientific publication record from 1910 to 2020 on two topics: "climate" and "climate change/global warming/climate emergency". The goal is to visualize how the publication record on these two topics has evolved over time, from different classification perspectives (year, country, source and organization). Three hypotheses are tested using data collected from Web of Science and various graphical representations of the data. It is found that research output related to the Earth’s contemporary changing climate overtook that of general climate research in 2011, and the publication ratio has been expanding in the last decade. There are significant differences in the publication countries and sources between the two topics, and conversely less significant differences in terms of organizations publishing these works. Differentiation factors that affect the level of research output and engagement on the climate challenge include: island versus landlocked nations, specialized versus general scientific journals, academic versus institutional organizations. The future of the publication records is discussed, such as the emergence of new terms to refer to the climate challenge, such as “climate emergency”.

With COVID-19 vaccines slowly being rolled out in many countries, it is important to understand the public’s acceptance of being vaccinated. This study aims to study the willingness and motivations among residents of the cities of Caloocan, Malabon, and Navotas, Philippines to be vaccinated against COVID-19. Based on an online survey of 137 respondents, who willingly participated in the study, 71% will take a COVID-19 vaccine if it becomes available, with similar rates among respondents from Caloocan (82%), Malabon (83 %), and Navotas (81%). If a vaccine is proven safe and effective, more respondents (82%) will take a COVID-19 vaccine. Furthermore, safety against COVID-19 as well as the safety and effectiveness of vaccines are the primary factors why respondents are willing or unwilling to get a vaccine. The results highlight the need for effective messaging that promotes COVID-19 vaccination, with emphasis on the safety and effectiveness of the vaccine, and its benefits to the public, especially that the vaccines that will be delivered in the country in the next few months are not the most preferred brands by the respondents.

Mayaro virus (MAYV) hijacks the host´s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPKs inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126 or Losmapimod were quantified using plaque assay. Also, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

Air pollution contributes to a critical environmental problem in various towns and cities. With the emergence of the smart cities concept, appropriate methods to curb associated with exposure to pollutants must have been a portion of appropriate urban development policy. This study presents a technologically driven air quality solution in smart cities to advertise energy-efficient and cleaner sequestration in these areas. It aims to address the issue of how to integrate the data-based strategies and artificial intelligence into efficient public sector pollution management in smart cities as a core part of the smart city definition. Exploratory research has been used in 152 smart cities, and environmental experts contributed to this study. It further addresses the technical criteria for implementing such a framework that the public administration uses to prepare the renovation of public buildings, minimize energy use and costs, and link these smart police stations to monitor air pollution as a part of integrated cities. Such a digital transition in resource management will increase public governance's energy performance, a higher standard of operation, and a healthier environment.

In the context of seismic risk, studying the characteristics of urban soils and of the built environment means adopting a holistic vision of the city taking a step forward compared to the current microzonation approach. Based on this principle, CLARA WebGIS aims to collect, organise, and disseminate the available information on soils and buildings in the urban area of Matera. The geodatabase is populated with i) 488 downloadable geological, geotechnical, geophysical, surveys; ii) geological, geomorphological, and seismic homogeneous microzones maps and iii) a new Digital Surface Model. The CLARA WebGIS (https://smartcities-matera-clara.imaa.cnr.it/) is the first publicly available database reporting for the whole urban area the spatial distribution of the fundamental frequencies for soils and the overlying 4043 buildings, along with probability levels of soil-building resonance. The WebGIS is addressed to a broad target of end users (local government, engineers, and geologists, etc.) as a support to the implementation of seismic risk mitigation strategies in terms of urban planning, seismic retrofitting, and management of post-earthquake crises. We recommend that the database be managed by local administrators, who would also have the task of deciding on future developments and continuous updating as new data becomes available.

Bangladesh has achieved tremendous progress in the fisheries sector that is making evidential contribution to food security, nutrition and livelihoods. Based on secondary data collected from the Department of Fisheries, Bangladesh and related un-published grey literature, this paper highlights the performance and challenges of the fisheries with emphasis on COVID-19 impact as well as the significance of this sector for achieving the Sustainable Development Goals (SDGs). The total fish production is increased more than six times over the last three decades (7.54 to 43.84 lakh MT) due to the dissemination of improved culture techniques and extension services. Inland closed water contributions have been increasing to 16.24%, while inland open water have declined 10.23% and marine fisheries have dropped 6.27% over the past 18 financial years (2000-2001 to 2018-2019). COVID-19, a major health crisis has also affects various issues associated with aquatic resources and communities. Transportation obstacles and complexity in the food supply, abstraction to start production, labour crisis, sudden illness, poor consumer demand, commodity price hike, creditor's pressure and reduced income were identified as affecting COVID-19 drivers. The combined effect of these drivers poses a significant threat to people’s income (SDG1- eliminate poverty), nutrition (SDG2- erase hunger), food security (SDG3- good health and wellbeing, and SDG12- responsible consumption and production) that demands comprehensive actions. Several recommendations have been elicited, which are important to implement for the achievement of SDGs as well management and imprvement of the aquatic sector (SDG14- life below and SDG16- life above water) .

Traumatic brain injury represents one of the main health problems in developed countries. Growth Hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for 4 days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury.

Abstract: Intensity of natural and man-made disasters is increasing day by day. Disaster is one of the major threats that affects the sustainable development of tourist attractions. Big data and Internet of Things(IoT) will greatly improve the disaster management. Based on the Big Data and IoT, a tourism attraction disaster management system is designed, divided into several stages namely pre-disaster early warning prevention, disaster mitigation, recovery and reconstruction after disaster and updating disaster planning. Then, the system flow is analysed, as well as the system structure is constructed. Additional, system function and its operation flow are introduced, including disaster warning, disaster relief, disaster assessment, real-time monitoring and supporting disaster planning functions. Finally, an application case is introduced. Research intends to improve tourism area disasters management.

Learning programming is a complex and challenging task for many students. It in-volves both understanding theoretical concepts and acquiring practical skills. Hence, analyzing learners’ data from online learning environments alone fails to capture the full breadth of stu-dents’ actions if part of their learning process takes place elsewhere. Moreover, existing studies on learning analytics applied to programming education have mainly relied on frequency analysis to classify students according to their approach to programming or to predict academic achieve-ment. However, frequency analysis provides limited insights into the individual time-related characteristics of the learning process. The current study examines students’ strategies when learning programming, combining data from the learning management system and from an au-tomated assessment tool. To gain an in-depth understanding of students’ learning process as well as of the types of learners, we used learning analytics methods that account for the temporal order of learning actions. Our results show that students have special preferences for specific learning resources when learning programming, namely slides that support search, and copy and paste. We also found that videos are relatively less consumed by students, especially while working on programming assignments. Lastly, students resort to course forums to seek help only when they struggle.

Peanut (Arachis hypogaea) contains allergenic proteins, which make it harmful to the sensitive population. The presence of peanut in foods must be indicated on label, to prevent accidental consumption by allergenic population. The development of suitable analytical methodologies to detect this allergen in processed foods is advisable. Real Time PCR allowed a specific and accurate amplification of allergen sequences. The optimal genome targets for specific and sensitive detection are those that show interspecific variation and high copy number. Some food processing methods could induce structural and/or conformational changes in proteins and produce the fragmentation and/or degradation of genomic DNA. In this work, we use chloroplast markers for specifically detection of peanut by Real Time PCR, in order to increase the sensitivity. Three different protocols of DNA isolation were evaluated, for total and organelle-DNA extraction. Binary mixtures of raw and processed peanut flour in wheat were performed at concentrations ranging from 100000 to 0.1 ppm. DNA isolation from peanut, mixtures and other legumes was carried out following three protocols for obtaining genomic and chloroplast-enrich DNA. Quantity and quality of DNA was evaluated, obtaining better results for protocol 2. Specificity and sensitivity of the method has been assayed with specific primers for three chloroplast markers (mat k, rpl16 and trnH-psbA) and Ara h 6 peanut allergen-coding region was selected as nuclear low-copy target and TaqMan probes. Efficiency and linear correlation of calibration curves were within the adequate ranges. Moreover, the influence of pressure and thermal processing on the peanut detectability was analyzed.

Insects possess an array of defense molecules allowing them to fight infections. They can also show a form of immune memory, named priming. However, the involvement of insect immune defense mechanisms in priming is unclear, since invertebrates lack the molecular machinery present in vertebrates to build an immune memory. In the red flour beetle Tribolium castaneum, larvae can be primed via the oral route with Bacillus thurigiensis var. tenebrionids (Btt). This results in changes in the expression of a large number of genes, among which some belong to families of ancient defense genes. In the present work, we tested whether three chosen candidate genes (a Thaumatin, a C-type Lectin and an Osiris-like gene) could be involved in the survival to a Btt exposure, as well as in the priming phenotype. We assessed changes in their expression over time and according to the priming treatment, knocked them down individually by RNA interference (RNAi), and observed how it affected survival upon challenge. The quantification of gene expression patterns in our larvae with RT-qPCR showed that up- and/or down-regulation of the genes, after the priming treatment, was quite volatile and time dependent. Upon knock-down, we did not observe the expected decrease in survival to Btt or the abolishment of the priming phenotype. We conclude that knocking down genes individually is probably insufficient to affect survival and priming in our system. This gives us insight into the complexity of the molecular processes underpinning priming.

Savouring is an emotion regulation strategy and intervention that focuses on the process of attending, intensifying and prolonging positive experiences and positive affect associated with these memories. Personal savouring involves a reflection on positive memories that are specific to the individual and do not involve others. In contrast, relational savouring entails reflecting on instances when people were responsive to the needs of their significant others. Such interventions hold potential to benefit parents of children with autism spectrum disorder (ASD). Mothers of children with ASD tend to experience higher anxiety, lower positive affect (PA) and more negative affect (NA) compared to mothers of neurotypical children, leading to a diminished overall well-being. Moreover, ASD has multiplied by up to four times in the recent decade. Thus, this paper investigates whether savouring may enhance the overall well-being of mothers of young children with ASD by increasing positive affect and decreasing negative affect. 52 mothers of neurotypical children and 26 mothers of children with ASD aged 3-7 years old were given a series of questionnaires and randomly assigned to either relational savouring or personal savouring conditions. In relational savouring, mothers were asked to reflect upon a shared positive experience with their child while in the personal savouring condition, a personal positive experience was recalled. Across mothers of children with ASD and neurotypical children, findings suggest that savouring leads to a decrease in NA (p &lt; .01) but not increases in PA. Similarly, mothers with higher levels of anxiety experience a greater decrease in NA (p &lt; .001) compared to mothers with lower levels of anxiety post-savouring. This study proposes that a brief savouring intervention may be effective among mothers of preschoolers. As lower levels of negative affect is linked to healthier psychological well-being, mothers might be able to engage in more effective and warm parenting after savouring exercises, which would cultivate positive mother-child relationships that benefit their children in the long-term.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Study of gross alpha (GA) and gross beta (GB) activity in road and surface deposited sediments were performed in various geographical areas in three Russian cities. To perform radiation measurements, new methods were applied which allow dealing with low mass and low volume dust size (2-100μm) samples obtained after the size fractionation procedure. The 2-10 μm fraction size has the highest gross beta activity concentration (GB)– 1.32Bq/g in Nizhny Novgorod (NN) and Rostov-On-Don (RND) while the 50-100 μm fraction size in Ekaterinburg. This is maybe associated with the subsistence of radionuclides that conveyed through natural processes and anthropogenic applications. The highest gross alpha activity concentration (GA) in fraction sizes was found in Rostov-on-Don city within the 50-100 μm– 0.22Bq/g. The fraction size 50-100 μmhas a higher gross alpha activity concentration than 2-10 and 10-50 μmfraction sizes due to natural partitioning of the main minerals constituting the urban surface deposited sediment (USDS). The geochemical processes that occur during the formation and transportation of USDS are reflected in the observed dependencies.Developed experimental methods of radiation measurements allowed to the extent the methodological base of urban geochemical studies.

Otolith morphology analysis is one of the main tools used for fish or fish stock identification. Moreover, otolith shape can also be used in fish dietary studies (stomach content) for the identification of prey fishes and their size according to the relationship between fish and otolith sizes. In the present study, the relationship between fish length and otolith morphological dimensions was investigated for the sabre squirrelfish, Sargocentron spiniferum (Forsskål, 1775) (family: Holocentridae). Samples of 185 fish were collected from the coast of the Red Sea, Egypt. To analyze the relationship between fish and otolith, otolith morphometric measurements (length, width, area, perimeter, weight, sulcus, and ostium) and shape factors (aspect ratio, compactness, form factor, rectangularity, roundness, ellipticity, squareness) describing outline shape were extracted using image analysis. Generalized linear models were applied for the relationship between body length and each otolith morphology feature. From the relationships between the total length of fish and fourteen morphology features, only otolith length, caudal length, and squareness were significantly correlated with fish size. Our results provide more information for the relationship between fish length and otolith morphometric features.

Postpartum hemorrhage is a complication during the puerperium that requires serious management, because it risks on threatening the mother's death. Currently, postpartum hemorrhage is still the main cause of maternal morbidity and mortality in the world. There is a need for a fast, precise and comprehensive handling effort involving all elements, such as the entire health team including doctors-nurses and families. The form of nursing intervention in postpartum hemorrhage patients can be in the form of nursing treatment or collaboration. The purpose of this review literature is to identify nursing treatment and nursing collaboration in postpartum hemorrhage patients as an effort to prevent maternal death. The writing method uses literature reviews by summarizing 10 articles publicated in 2019, 2020 and 2021 in 4 search data bases including Sciencedirect, Scopus, Proquest and Thompson. The review guidelines used are based on Prisma and the Joanna Briggs Institutute. The level of eligibility is identified through the title, abstract, research methodology and full text. The results of the reviews found are presented in a narrative form. The results of the review study found that there were 10 articles on postpartum hemorrhage management measures both in the effort of snoring treatment and collaboration including: optimizing the competence of service providers based on E_Learning , foot reflexology since the 4th stage of labor, 800 mcg sublingual Misoprostol, the use of the Digital Postpartum Hemorrhage Management Device ( DPHMD), bilateral-contralateral cervical clamps, suction tube uterine tampons, bilateral hypogastric artery (BHAL), evaluation of Shock Index, Carbetocin drugs and administration of Tranexamic acid 1 gram IV within 10 minutes of vaginal delivery. The conclusion of this review literature is that nursing treatment and nursing collaboration are proven to have a positive impact as an effort to prevent death in postpartum hemorrhage patients.

Tree decline resulting from climate change results in physiological weaknesses, attack by harmful pests and pathogen, and threatens forest ecosystem stability. In the work described here, the effects of drought on wood density, tree ring width, and variations in vessel morphology were investigated in Persian oak (Quercus brantii) in the forests of the Zagros Mountains, Ilam province, western Iran. Radial discs were cut from trunks of declined and healthy trees and wood blocks cut radially from the sapwood, heartwood, and juvenile core. Observations were made on transverse sections from the blocks using microscopy. In trees with decline symptoms, wood density was greater than the healthy trees. Furthermore, declining trees had the narrowest ring width, reduced vessel diameter, vessel area, and highest number of vessels and tylose in pith towards bark. It was concluded that changes in anatomical features are associated with the weakening of the trees and are components in declining tree health.

The purpose of this article was to check the effects on health of various types of physical activities, diet, BMI, smoking and alcohol consumption and their interrelationships with control for age, sex and level of education. The study was based on epidemiological data (9617 participants from 19 to 81 years old for whom we have health indicators over a period of 11 years) together with questionnaires about diet, alcohol, tobacco and the frequency of different types of physical activities. Descriptive statistics and non-parametric correlational analysis of epidemiological data was performed with use of SPSS v.19. Our results indicate the existence of the significant relationship between leading a healthy life style (type of physical activities, limitations of fats consume and weight maintenance). However, the different categories of physical activities were analysed separately and showed slight differences on health indicators impacts. Our findings confirm that leading a healthy life style (all types of physical activities, limitations of fats consume and weight maintenance) is an important issue since it has a significant relationship with physical and mental health indicators, but outdoor physical activities and practicing sport in group have shown slightly higher impact on health.

The reconstruction of land use practices in hyper arid Saharan Africa is often hampered by the accuracy of the available tools and by unconscious biases that see these areas as marginal and inhospitable. Considered for a long time the living space of pastoral mobile communities, new research is showing of agriculture might have been more important in these areas than previously thought. In this paper, after a review of present-day land use strategies in Saharan Africa, we show how ethnographic and ethnoarchaeological data can offer us a different point of view and help in better defining land use and food production strategies in this area. Ultimately, these insights can be integrated into the ongoing effort of reconstructing past land use globally.

Worldwide initiatives currently aim to reduce free sugar intakes, but success will depend on consumer attitudes towards sugar and the alternatives. This work aimed to explore attitudes towards sugar, sweeteners and sweet-tasting foods in the general public of the UK, including attitudes towards personal consumption and related policies. Focus groups and interviews were conducted with 34 adults (7 males, ages: 18-65 years). Thematic analysis identified six themes: ‘Value’ (e.g. pleasure, emotions), ‘Angle’ (e.g. disinterest), ‘Personal Relevance’ (to be concerned and/or change one’s own behaviour), ‘Personal Responsibility’ (one has an active relationship with these food items), ‘Understanding’ (the acquisition, comprehension and application of information surrounding these food items) and ‘It’s Not Up to Me’ (a passive approach towards these food items, because intake is subjected to other factors). Both positive and negative attitudes towards sugar, sweeteners and sweet-tasting foods were expressed in all themes, largely dependent on the individual. Potential strategies for reducing free sugar intakes were also reported, but differences in likely value were suggested by different individuals. Future work should assess associations between attitudes and intakes. For greatest population benefit, evidence of the dominant attitudes in those in greatest need of reduced free sugar intakes would be of value.

Background: CoronaVirus Disease 2019 (COVID-19) is the main discussed topic world-wide in 2020 and at the beginning of the Italian epidemic, scientists tried to understand the virus diffusion and the epidemic curve of positive cases with controversial findings and numbers. Objectives: In this paper, a data analytics study on the diffusion of COVID-19 in Lombardy Region and Campania Region is developed in order to identify the driver that sparked the second wave in Italy Methods: Starting from all the available official data collected about the diffusion of COVID-19, we analyzed google mobility data, school data and infection data for two big regions in Italy: Lombardy Region and Campania Region, which adopted two different approaches in opening and closing schools. To reinforce our findings, we also extended the analysis to the Emilia Romagna Region. Results: The paper aims at showing how different policies adopted in school opening / closing may have on the impact on the COVID-19 spread. Conclusions: The paper shows that a clear correlation exists between the school contagion and the subsequent temporal overall contagion in a geographical area.

One of the non-linear phenomena that affect high bandwidth and long reach communication systems is the non-linear phenomenon called four-wave mixing (FWM). Unfortunately, the simulation of such systems aiming to obtain their design parameter limitations require more time as the number of channels increases. In this paper, we propose a new high-performance computational model to obtain optimal design parameters in a multi san Dense Wavelength Division Multiplexing (DWDM) system, limited by FWM and the intrinsic Amplified Spontaneous Emission (ASE) noise of optical amplifiers employed in each segment. The simulation in this work provides a complete optical design characterization and compares the efficiency and speed improvement of the proposed parallelization model versus a previous sequential model. Additionally, an analysis of the computational complexity of parallel model is presented, where two parallel implementations are used. First, Open Multi−Processing (OpenMP), based on the use of a central, multi-core processing unit is used and secondly the Compute Unified Device Arquitecture (CUDA), which is based on the use of graphics processing unit. Results show that parallelism improves to up to 40 times the performance of the simulation when nested parallelization with CUDA is used, over de sequential method and up to 6 times compared with the implementation with OpenMP using 12 processors. Within our parallel implementation, it is possible to simulate with an increased number of channels, that was unpractical in the sequential simulation.

Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity.Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex.Methods: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD.Results: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP.Conclusions: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis but little is known about the molecular mechanisms involved. The recently developed HDV mouse model based on the delivery of HDV replication-competent genomes using adeno-associated vectors (AAV) develop a liver pathology very similar to the human disease, and allowed us to perform mechanistic studies. We have generated different AAV-HDV mutants to eliminate the expression HDV antigens (HDAgs), characterized them both in vitro and in vivo. We confirmed that S-HDAg is essential for HDV replication and cannot be replaced by L-HDAg or host cellular proteins, and the L-HDAg is essential for HDV infectious particle production. We have also found that the lack of L-HDAg resulted in the increase of of S-HDAg expression levels and the exacerbation of liver damage which is T cell independent but is associated with an increment in liver inflammation. Interestingly, early expression of L-HDAg significantly ameliorated the liver damage induced by the mutant expressing only the S-HDAg. In summary, the use of AAV-HDV represents a very attractive platform to interrogate in vivo the role of viral components in the HDV life cycle and to better understand the mechanism of HDV-induced liver pathology.

Significant earthquakes frequently occur in Indonesia. Indonesia is situated over three active tectonic plates, resulting in the formation of faults and trenches on the land and ocean floor. For the last 120 years since 1900, there have been more than 1,250 significant earthquake events in Indonesia. In this study, we analyse Indonesia's significant earthquake events using geostatistical and geovisualisation methods to produce an appropriate geospatial analysis platform using the RShiny package to build the WebGIS application. The results show that the earthquake events were spatially distributed from the Sumatera fault in the western part of Indonesia to the southern part of Indonesia, where the Java trench was located and the eastern part of Indonesia. The WebGIS application received a positive evaluation by respondents, with a mean value of 1.617 for pragmatic quality, 1.808 for hedonic quality, and 1.713 for overall quality. This means that the WebGIS application is of good quality based on respondents' impressions. The users also more easily gained insight into information as a result of geostatistical methods. The information gained by the users during the user interaction with the WebGIS platform overlapped with the information that the researcher started with, that is, the spatial cluster of significant earthquakes in Indonesia.

The cyclic regeneration of human endometrium is guaranteed by the proliferative capacity of Endometrial Mesenchymal Stromal Cells (E-MSCs). Due to this, the autologous infusion of E-MSCs has been proposed to support endometrial growth in a wide range of gynecological diseases. We aimed to compare two different endometrial sampling methods, the surgical curettage and the Vacuum Aspiration Biopsy Random Assay, and to validate a novel xeno-free method to culture human E-MSCs. Six E-MSCs cell lines were isolated after a mechanical tissue homogenization and cultured using human platelet lysate. E-MSCs were characterized for the colony formation capacity, proliferative potential and multilineage differentiation. The expression of mesenchymal and stemness markers was tested by FACS analysis and Real-Time PCR, respectively. Chromosomal alterations were evaluated by karyotype analysis, whereas tumorigenic capacity and invasiveness were tested by soft agar assay. Both endometrial sampling techniques allowed to efficiently isolate and expand E-MSCs using a xeno-free method preserving their mesenchymal and stemness phenotype, proliferative potential and multi-lineage differentiation ability during the culture. No chromosomal alterations and invasive/tumorigenic capacity were observed. Herein we report the first evidence of efficient E-MSCs isolation and culture in Good Manufacturing Practice compliance conditions, suggesting Vabra endometrial sampling as alternative to surgical curettage.

Background The World Health Organization has recently recognized Long COVID, calling the international medical community to strengthen research and comprehensive care of patients with this condition. However, if Long COVID pertains to children as well is not yet clear. Methods An anonymous, online survey was developed by an organization of parents of children suffering from persisting symptoms since initial infection. Parents were asked to report signs and symptoms, physical activity and mental health issues. Only children with symptoms persisting for more than four weeks were included. Results 510 children were included (56.3% females) infected between January 2020 and January 2021. At their initial COVID-19 infection, 22 (4.3%) children were hospitalized. Overall, children had persisting COVID-19 for a mean of 8.2 months (SD 3.9). Most frequent symptoms were: Tiredness and weakness (444 patients, 87.1% of sample), Fatigue (410, 80.4%), Headache (401, 78.6%), Abdominal pain (387, 75.9%), Muscle and joint pain (309, 60.6%), Post-exertional malaise (274, 53.7%), rash (267, 52.4%). 484 (94.9%) children had had at least four symptoms. 129 (25.3%) children have suffered constant COVID-19 infection symptoms, 252 (49.4%) have had periods of apparent recovery and then symptoms returning, and 97 (19.0%) had a prolonged period of wellness followed by symptoms. Only 51 (10.0%) children have returned to previous levels of physical activity. Parents reported a significant prevalence of Neuropsychiatric symptoms. Conclusions Our study provides further evidence on Long COVID in children. Symptoms like fatigue, headache, muscle and joint pain, rashes and heart palpitations, and mental health issues like lack of concentration and short memory problems, were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. A better comprehension of Long COVID is urgently needed..

Machine learning (ML) has a large capacity to learn and analyze a large volume of data. This study aimed to train different algorithms to discriminate between healthy and pathologic corneal images by evaluating digitally processed spectral-domain optical coherence tomography (SD-OCT) corneal images. A set of 22 SD-OCT images belonging to a random set of corneal pathologies was compared to 71 healthy corneas (control group). A binary classification method was applied; three approaches of ML were used. Once all images were analyzed, representative areas from every digital image were also processed and analyzed for a statistical feature comparison between healthy and pathologic corneas. The best performance was obtained from transfer learning - support vector machine (TL-SVM) (AUROC = 0.94, SPE 88%, SEN 100%) and transfer learning – random forest (TL- RF) method (AUROC = 0.92, SPE 84%, SEN 100%), followed by convolutional neural network (CNN) (AUROC = 0.84, SPE 77%, SEN 91%) and random forest (AUROC = 0.77, SPE 60%, SEN 95%). The highest diagnostic accuracy in classifying corneal images was achieved with the TL-SVM and the TL-RF models. In image classification, CNN was a strong predictor. This pilot experimental study developed a systematic mechanized system to discern pathologic from healthy corneas.

System-of-systems (SoS) approach is often used for simulating disruptions to business and infrastructure system networks allowing for integration of several models into one simulation. However, the integration is frequently challenging as each system is designed individually with different characteristics, such as time granularity. Understanding the impact of time granularity on propagation of disruptions between businesses and infrastructure systems and finding the appropriate granularity for the SoS simulation remain as major challenges. To tackle these, we explore how time granularity, recovery time, and disruption size affect the propagation of disruptions between constituent systems of an SoS simulation. To address this issue, we developed a High Level Architecture (HLA) simulation of 3 networks and performed a series of simulation experiments. Our results revealed that time granularity and especially recovery time have huge impact on propagation of disruptions. Consequently, we developed a model for selecting an appropriate time granularity for an SoS simulation based on expected recovery time. Our simulation experiments show that time granularity should be less than 1.13 of expected recovery time. We identified some areas for future research centered around extending the experimental factors space.

This study assessed stakeholders’ perception on the prospects and challenges of practising Climate–Smart Agroforestry in the Asunafo North Municipal Assembly in the Ahafo Region in Ghana. Interviewer administered questionnaires were used to collect cross-sectional data from 250 cocoa, food and cash crop farmers drawn from four (4) communities using simple random sampling. And nine (9) in-depth interviews were also conducted to elicit key stakeholder perspectives. Stakeholders also held the view that Climate-Smart Agroforestry encourages the use of stress-tolerant crop varieties, increase income, improve soil productivity, diversify farm produce, urges the reduction of input supply and recommends the timely usage of the inputs, ensures better market system for farm produce, cost of production decreases during the practice of Agroforestry, agro-ecological functions and Climate-Smart Agroforestry can best help adapt to the threats of climate change in the agriculture sector. The challenges included insecure tree ownership right, fast-declining soil fertility and long maturity period of Agroforestry trees, land tenure issues, illegal tree logging (chainsaw operators) on farms, lack of practical understanding of the approach, inadequate knowledge and information and inadequate supportive facilities in the study area. The study recommends further studies on the existing forest policy and legislations and its implications on the practice and adoption of Climate-Smart Agroforestry in respond to climate change in the area.

Marine invertebrates are model organisms in several areas of biological sciences, being a source of massive biological information. Although, the scientific relevance of marine invertebrates, the research with them can be limited for their tissue characteristics and troubles for the replication of physical and chemical properties of seawater. Thence, the main goal of this laboratory workflow is to provide a useful methodological approach to reduce the experimental limitations during the study of marine invertebrates. The present study describes experimental methodologies for the collection, transport, and maintenance of sessile tunicates. Also, an approach to observe and characterize, a diverse population of blood cells in marine invertebrates, by several cytological stains and electron microscopy. Lastly, suggestions and protocols to extract quality RNA from samples with high concentrations of salts, pigments, secondary metabolites, and polysaccharides. This methodological approach can be easily adapted to other marine invertebrates, moreover uses low-cost reagents and widely available laboratory equipment. Making possible the study of different types of marine animals in diverse locations.

Knee Osteoarthritis (KOA) is a chronic disease characterized by progressive disability and joint pain. Meniscus chondrocytes apoptosis is the main cause of reduced chondrocyte number and self-repair function. The purpose of this study was to investigate the role of miR-27b-3p in KOA.In this study, we found that the expression of miR-27b-3p was downregulated in cultured IL-1β treated chondrocyte and cartilage tissues in KOA. KOA overexpression evidently reduced IL-1β induced chondrocyte apoptosis and caspase-3 and caspase-9 expression.The upregulated iNOS and COX-2 mRNA and proteins expression was also inhibited by miR-27b-3p mimics. The expression of nitric oxide, PGE2, TNF-α and IL-6 was also inhibited by miR-27b-3p mimics. The target gene of miR-27b-3p was confirmed to be BDNF. TrkB/CREB pathway was proved to be the downstream pathway of miR-27b-3p/BDNF axis.The apoptotic cell percentage and nitric oxide, PGE2, TNF-α and IL-6 expression was induced by BDNF+IL-1β. This induction was inhibited by miR-27b-3p mimics. The cartilage tissues stained with safranin O results showed miR-27b-3p greatly decreased KOA induced cartilage degradation. The expression of BDNF、TrkB and p-CREB was inhibited by len-miR-27b-3p. MiR-27b-3p also reduced the expression of TNF-α、IL-6 and Bax, and increased Bcl-2 expression. These results indicated miR-27b-3p could applied to inhibit the development of KOA and miR-27b-3p/BDNF/TrkB/CREB pathway could serve as novel treatment target to handle KOA.

Respiratory Syncytial Virus (RSV) causes severe inflammation and airway pathology in children and the elderly by infecting the epithelial cells of the upper and lower respiratory tract. RSV replication is sensed by intracellular pattern recognition receptors upstream of the IRF and NF-B transcription factors. These proteins coordinate an innate inflammatory response via Bromodomain containing protein 4 (BRD4), a protein that functions as a scaffold for unknown transcriptional regulators. To better understand the pleiotropic regulatory function of BRD4, we examine the BRD4 interactome and identify how RSV infection dynamically alters it. To accomplish these goals, we leverage native immunoprecipitation and Parallel Accumulation – Serial Fragmentation (PASEF) mass spectrometry to examine BRD4 complexes isolated from human alveolar epithelial cells in the absence or presence of RSV infection. In addition, we explore the role of BRD4’s acetyl-lysine binding bromodomains in mediating these interactions by using a highly selective competitive bromodomain inhibitor. We identify 101 proteins that are significantly enriched in the BRD4 complex and are responsive to both RSV-infection and BRD4 inhibition. These proteins are highly enriched in transcription factors and transcriptional coactivators. Among them, we identify members of the AP1 transcription factor complex, a complex important in innate signaling and cell stress responses. We independently confirm the BRD4/AP1 interaction in primary human small airway epithelial cells. We conclude that BRD4 recruits multiple transcription factors during RSV infection in a manner dependent on acetyl-lysine binding domain interactions. This data suggests that BRD4 recruits transcription factors to target its RNA processing complex to regulate gene expression in innate immunity and inflammation.