Constraint-based metabolic modeling approaches have enhanced our knowledge and understanding of the metabolism of prokaryotes and eukaryotes. This approach highly depends on the reconstruction process of genome-scale metabolic models (Mmodels). M-models can guide effective experimental design and yield new insights into the function and control of biological systems. Despite the recent advances in the automated generation of draft metabolic network reconstructions, the manual curation of these networks remains a labor-intensive and challenging task. Thus, these ten quick tips for the manual curation process are essential for optimizing high-quality metabolic model generation in less time. This collection of tips describes in great detail the resources and methods to ensure successful reconstruction. Furthermore, it increases the scope of other protocols of metabolic modeling by including resources to reconstruct eukaryotic organisms. Thus, all tips are applicable to a wide range of eukaryotic organisms. We believe this manuscript will interest a broad audience and researchers from different disciplines, spanning from microbiology and systems biology to biotechnology.

In recent decades, porous scaffolds for bone tissue engineering (BTE) have gained significant attention. Considerable research efforts have been dedicated to investigating the impact of scaffold pore size on a diverse array of biological processes, including cell-scaffold interactions, substance transportation, and vascularization. However, the multi-scale hierarchical porosity, a key structural characteristic of natural bone, has rarely been replicated in BTE scaffolds due to the challenges of controlling the scaffold structure across multiple length scales. With the advancement of manufacturing technology, there has been increasing research on biomimetic multi-scale hierarchical materials, which are also gaining favor in the field of BTE. Therefore, there is an urgent need to review multi-scale hierarchical porous BTE scaffolds. This paper aims to review the role and fabrication methods of multi-scale porous BTE scaffolds at different length scales, the design and manufacturing of new BTE scaffolds for bone regeneration.

Evaluating the performance of water indices and mapping the spatial distribution of water-related ecosystems are important for monitoring surface water resources. This is particularly the case for Ethiopia since there is limited information available on water resources development over time despite its relevance for the people and ecosystems. To address this problem, this paper evaluates the performance of seven water indices for country-scale surface water detection based on high spatial and multi-temporal resolution Sentinel-2 data, processed using the Google Earth Engine cloud computing system. Results show that the water index (WI) and automatic water extraction index with shadow (AWEIsh) are the most accurate ones to extract surface water. Comparisons are based on qualitative visual inspections and quantitative accuracy indicators. For the latter, WI and AWEIsh obtained kappa coefficients of 0.96 and 0.95, respectively, and an overall accuracy of 0.98 each. Both indices accounted for similar spatial coverages of surface waters with 82,650 km2 (WI) and 86,530 km2 (AWEIsh) for the whole of Ethiopia.

Grazing exclusion (GE) and rest grazing (RG) are important management to restore grassland ecosystems. In order to evaluate the effects and mechanisms of different grazing management on species diversity, vegetation community indices and soil variables were determined in the plots of Qilian Mountains in Gansu Province. The results showed that diversity effects and their regulating mechanisms had space-scale dependence under different grazing management. Species richness and species diversity indices of RG in grassland were significantly higher than that of GE at the regional scale. Additionally, three grazing management in mountain meadows had only a significant effect on species richness, but different management in mountain meadows and temperate steppes had a significantly different effect on species diversity indices. Meanwhile, soil variables only influenced species diversity at the regional scale. Most of community and soil variables at each scale had positive effects on species diversity, except that the direction of biodiversity effects was negative for species coverage, mean plant height, soil porosity (SK) and bulk density (BD) under two contrasting grazing management. In conclusion, choosing RG at the regional scale and select grazing management according to different grassland types at the local scale to restore degraded grassland vegetation.

Outcome of redo-mitral valve replacement in the small mitral annulus with the use of the chimney technology is not well documented. From 2019 to 2020, 77 consecutive patients underwent redo-mitral valve replacement with the use of the chimney technology because of a small mitral annulus. To evaluate heart structural integrity and clinical outcomes, postoperative clinical data and echocardiograms were examined. Mean age was 56.7 ± 15.98 years. All patients underwent mitral valve surgery of which 62 were mitral valve replacements, 7 mitral valve repairs, and 8 double valve replacements. Preoperative Mitral valve mean gradient was 18.07 ± 9.40 mmHg. Postoperative mitral prosthesis size 28.51 ± 1.22 mm. The median increment of mitral size enlargement was 4 (0, 6) valve sizes. Mean mitral gradient coming out of the operating room was 10.34 ± 2.12 mmHg and at follow-up echocardiogram performed at 3 years after the procedure was 10.36 ± 1.70 mmHg. One-year survival was 93.3%, while 4-year survival was 89.3% with no reoperation. Use of the chimney technology in small mitral valve re-mitral valve replacement results in larger valve sizes. Moreover, the mean gradients over the mitral valve are acceptable intraoperatively and over time.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.

This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

Anastomosing rivers are wetland systems with multiple channels, and there are many constraints limiting in-situ observations of their hydrodynamics. Therefore, there are few reports on the hydrodynamic data of such rivers. In order to obtain the hydrodynamic parameters of the river channels without hydrological observations in the anastomosing rivers, this study proposes an expression method namely expression of channel morphological parameters (ECMP) for hydrodynamic calculations. The calculation formula of the ECMP method based on the shape factor, scale factor, and gradient factor of the flow cross-section as independent variables. This method can be used to calculate the average velocity, discharge, specific stream power, gross stream power and other hydrodynamic parameters of the flow cross-section at different water levels, only requiring the measurement of morphological parameters such as the average depth, width-depth ratio, and gradient of the flow (channel) cross-section. The applicability of the ECMP method was verified using measured hydrological data. The results show that the ECMP method is a practical calculation method with high computational accuracy and convenient application for calculating river hydrodynamic parameters. It has great application value in study on fluvial geomorphology and hydrodynamics, as well as in the reconstruction of ancient river hydrology and hydrodynamics.

We performed Bayesian network meta-analysis (NMA) to suggest frontline treatments for patients with high PD-L1 expression (at least 50%). A total of 5,237 patients from 22 studies were included in this NMA. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference of survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for NSCLC with high PD-L1 expression. Considering there was no significant difference of survival outcomes among treatment regimens incorporating immunotherapy and ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, however, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression and no targetable aberrations.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated to their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

Acacia dealbata Link, named Mimosa in Portugal, is an invasive hardwood species with potential for construction use, but research is limited. The available stock of small-diameter juvenile wood (sjw) logs can help reduce this gap, but tangential cracking at log ends challenges fastener connections. This study evaluated different treatments to control and reduce end-face cracking in sjw logs during air drying, an economical and environmentally friendly procedure. Extreme two-thirds of sixteen Mimosa logs were subjected to two treatments: one with longitudinal kerfs 15 mm deep along the length (2 and 3 kerfs) and the other with a hollow in the centre up to half the length (16 mm and 30 mm diameters). Over 219 days of air drying and compared with the central part, kerfing treatments significantly reduced outer wood tangential cracking (p < 0.001), with the 3-kerf also reducing crack numbers (p < 0.05) but increasing significantly cracks near the pith (p < 0.01). The 30 mm central hollow significantly reduced central perforation cracking (p < 0.05). Results suggest that a combined treatment approach could help mitigate cracking, enhancing the suitability of wild Mimosa logs for construction use.

Background: Although cerebral aneurysm (CA) is a defining complication of COL4A1/2-related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors. Methods: We described a family presenting with a novel variant in the COL4A1 gene complicated with CA. Concurrently, an exhaustive review of previously documented patients with COL4A1/2-related vasculopathy was conducted by sourcing data from PubMed, Web of Science, Google Scholar, and Ichushi databases. We compared the variant types and locations between patients with CA (positive group) and those without CA (negative group). Results: This investigation encompassed 53 COL4A1/2 variants in 76 patients. Except for one start codon variant, all the identified variants in CA were missense variants. Otherwise, CA was not associated with other clinical manifestations, such as small-vessel disease or other large-vessel abnormalities. A higher frequency of missense variants (95.5% vs 58.1%, p = 0.0035) was identified in the CA positive group. Conclusions: CA development appears to necessitate qualitative alterations in COL4A1/2, and the underlying mechanism seems independent of small vessel disease or other large vessel anomalies. Our findings suggest that a meticulous evaluation of CA is necessary when missense variants in COL4A1/2 are identified.

We develop the theory of Heyting locally small spaces, including Stone-like dualities such as a new version of Esakia duality and a system of concrete isomorphisms and equivalences. In such a way, we continue building tame topology, realising Grothendieck's ideas. We use up-spectral spaces and define the standard up-spectralification of a Kolmogorov locally small space. This research gives more understanding of locally definable spaces over structures with topologies.

Land degradation is a critical issue globally putting our future generations at risk. The decrease in farm productivity over the years is evidence of land degradation severity in Nepal. Among the many strategies in place, agroforestry, which is an integrated tree-based farming, is widely recommended to address this productivity issue. This paper thoroughly examines what influences the choice of agroforestry adoption by farmers and what discourages the adoption. For this, a total of 288 households were surveyed using a structured questionnaire. Two agroforestry practices were compared with conventional agriculture with the help of the Multinomial Logistic Regression (MNL) model. The likelihood of adoption was found to be influenced by gender; the male-headed households were more likely to adopt the tree-based farming practice. Having a source of off-farm income was positively associated with the adoption decision of farmers. Area of farmland was found being the major constraint to agroforestry adoption for smallholder farmers. Some other variables that affected positively included livestock herd size, provision of extension service, home-to- forest distance, farmers’ group membership and awareness of farmers about environmental benefits of agroforestry. Irrigation was another adoption constraint that the study area farmers were faced with. The households with means of transport and with larger family (household) size were found to be reluctant towards agroforestry adoption. A collective farming practice could be a strategy to engage the smallholder farmers in agroforestry.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

The effects of rare earth Y content on the microstructure and high-temperature oxidation properties of 47Fe-36Ni-15Cr-1.5Mn alloy at 1000°C were investigated. The results show that 47Fe-36Ni-15Cr-1.5Mn alloy oxidizes at 1000°C under laboratory atmospheric pressure to form an oxide film layer dominated by Cr2O3 and (Fe, Ni, Mn) Cr2O4 spinel, and the oxidation curve of the alloy follows the parabolic law. After the addition of rare earth Y, rare earth phases precipitated along the grain boundaries in the alloy, and the more Y content, the more precipitated phases in the grain boundaries. The alloy with added rare earths was oxidized at a high temperature of 1000 °C for 2160 min, the oxidation law still followed the parabolic law, while the rare earth phase at the grain boundary reacted with the oxygen atoms infiltrated from the outside to generate a rare earth Y-rich oxide residing at the boundary between the grain boundary and the precipitated phase of the alloy. Add 0.5 wt.% rare earth Y 47Fe-36Ni-15Cr-1.5Mn-0.5Y alloy 1000 ° C high temperature oxidation of the formation of spinel oxide crystalline particles, dense and complete oxide film layer, the surface of the addition of a small amount of (0.5 wt.%) rare earth Y after the refinement of the oxide particles, and in the alloy grain boundaries in the form of oxides reside in the alloy to inhibit the cations in the matrix and the oxygen negative ions. and oxygen-negative ions in the alloy matrix, improving the antioxidant performance of the alloy. With the further increase of rare earth Y, during the oxidation of the alloy at high temperature, the precipitation phase at the grain boundary promotes the inward diffusion of oxygen, resulting in the deterioration of the antioxidant property of the alloy.

The characteristics of the eddy mass transport are estimated depending on the values of the parameters of a large-scale flow that forms under the conditions of the shelf seas in the Arctic. For this, the results of numerical simulation of the Kara Sea with a horizontal resolution permitting the development of mesoscale eddies are used. The parameters resulting from numerical experiment are considered as a statistical sample and are analyzed using methods of sensitivity study and clustering of sample elements. Functional dependencies are obtained that are closest to the simulated distributions of quantities. These expressions make it possible, within the framework of large-scale models, to evaluate the characteristics of the cross-isobatic eddy mass transport in the diffusion approximation with a counter-gradient flux. Numerical experiments using the SibCIOM model showed that areas along the Fram branch of the Atlantic waters trajectory in the Arctic as well as the shelf of the East Siberian and Laptev seas with adjacent deep water areas are most sensitive to proposed parameterization of eddy exchanges. Accounting for counter-gradient eddy fluxes turned out to be less important.

Phylogenetic tree analysis is commonly used to understand the evolutionary distance between different species or strains of the same species. This work originally aimed to gain an understanding and visual depiction of the evolutionary distance in 23S rRNA gene of different Helicobacter pylori strains. Using an in-house MATLAB multiple sequence alignment and phylogenetic tree analysis software, the phylogenetic tree constructed for 23S rRNA gene reveals two major lineages with further subdivisions in each cluster. This suggests two major evolutionary forces driving the evolution of the 23S rRNA gene. In comparison, there is relatively short evolutionary distance in the 16S rRNA gene phylogenetic tree of H. pylori, suggesting lack of major evolutionary forces driving mutational changes of the gene. Overall, the data suggests that the large ribosome subunit which houses the 23S rRNA of H. pylori is undergoing significant conformational changes that may be a response to the frequent use of various antibiotics that target the ribosome of H. pylori.

Typhoons bring great damages to transmission line systems located in coastal areas. Strong wind and extreme precipitation are the main sources of damaging effects. Transmission lines suffered from wind-driven rain exhibit more susceptibility to damage due to the coupled effect of wind and rain water. This paper presents an integrated numerical simulation framework based on mesoscale WRF model, multiphase CFD model and FEM model to analyze the motions of a transmission line subjected to coupled wind and rain loads during typhoon events. A full-scale transmission line in Zhoushan island is employed to demonstrate the effectiveness of the proposed framework by simulating typhoon evolution in terms of wind fields and rainfall, solving the coupled wind and rain fields around the conductor and predicting the dynamic responses of the transmission line during Super Typhoon Lekima (2019). The results show that the horizontal displacements of the transmission line under the joint actions of wind and rain increases approximately 17%~18% compared to those of wind loads only. It is important to consider the coupled effects of wind-driven rain on conductors in the design of transmission lines under typhoon conditions.

Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism. PHs classification based on gene mutations parallel a variety of enzymatic defects, and all involve the harmful accumulation of calcium oxalate crystals that produce systemic damage. These geographically widespread rare diseases have a deep impact in the life quality of the patients. Until recently, treatments were limited to palliative measures and kidney/liver transplants in the most severe forms. Efforts made to develop pharmacological treatments succeeded with the biotechnological agent lumasiran, a siRNA product against glycolate oxidase, which has become the first effective therapy to treat PH1. However, small molecule drugs have classically been preferred since they benefit from experience and have better pharmacological properties. The development of small molecule inhibitors designed against key enzymes of glyoxylate metabolism is on the focus of research. Enzyme inhibitors are successful and widely used in several diseases and their pharmacokinetic advantages are well known. In PHs, effective enzymatic targets have been determined and characterized for drug design and interesting inhibitory activities have been achieved both in vitro and in vivo. This review describes the most recent advances towards the development of small molecule enzyme inhibitors in the treatment of PHs, introducing the multi-target approach as a more effective and safe therapeutic option.

Serine/threonine kinase (AKT) signaling regulates diverse cellular processes and is one of the most important aberrant cell survival mechanisms associated with tumorigenesis, metastasis, and chemoresistance. Targeting AKT has become an effective therapeutic strategy for the treatment of many cancers. AKT3 (PKBγ), the least studied isoform of the AKT family, has emerged as a major contributor to malignancy. AKT3 is frequently overexpressed in human cancers, and many regulatory oncogenic or tumor suppressor small non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have recently been identified to be involved in regulating AKT3 expression. Therefore, a better understanding of regulatory miRNA/AKT3 networks may reveal novel biomarkers for diagnosis of patients with cancer and provide invaluable information for developing more effective therapeutic strategies. The aim of this review is to summarize current research progress in the isoform-specific functions of AKT3 in human cancers and the roles of dysregulated miRNA/AKT3 in specific types of human cancers.

Autoantibodies against specific lung cancer-associated antigens have been suggested for lung cancer diagnosis. This study aimed to evaluate the diagnostic performance of anti-gen-autoantibody immune complex (AIC) against its free antigens for CYFRA21-1, ProGRP, NGAL, and NSE in non-small cell lung cancer (NSCLC). In total, 85 patients with NSCLC and 120 healthy controls (HCs) were examined using a 9G DNA chip method. The ratios of AICs to their antigens and combinations of ratios consisting of two to four markers were calculated. The levels of AICs for CYFRA21-1, ProGRP, NGAL, and NSE were higher than their free antigens in all participants. The levels of each free antigen distinguished patients with NSCLC from HCs. The ratios of AIC to its antigen and seven combinations consisting of two to four ratios were significantly higher in patients with NSCLC than those in HCs. Excellent diagnostic performance was observed for all combination ratios (C4-1), with 85.9% sensitivity and 86.7% specificity at cutoff 3.51. Higher sensitivity was observed in the very early stages (0–I) and adenocarcinoma than in stages II–IV and other pathological types. The combination of all ratios of AICs and their antigens for all four markers is useful in the diagnosis of NSCLC.

To address the severe distresses of asphalt pavement, a new type of pavement maintenance treatment, porous ultra-thin overlay (PUTO) with small particle size was proposed. The PUTO has a thickness of 1.5~2.5 cm and a large void ratio of 18~25%. As a newly asphalt mixture, the structure characteristics differ from traditional pavement. Therefore, it is necessary to investigated the fabrication schemes in laboratory and on-site, respectively. In this study, the optimal fabrication schemes, including compaction temperature and number of blows of PUTO were determined based on Cantabro test and volumetric parameters. Then, the corresponding relationship between laboratory and on-site compaction work was then established based on the energy equivalent principle. On this basis, the numbers of on-site rolling passes and the combination method were calculated. The results show that increased compaction temperature and number of blows reduce the height and enhance the compactness of the Marshall sample. With the same temperature and number of blows, the scattering resistance of coarse gradation (PAC-1) is better than that of fine gradation (PAC-2), and the increased asphalt viscosity significantly improves the scattering resistance of the asphalt mixture. To ensure the scattering resistance and volumetric characteristic, the initial compaction temperature of the PAC-1 and PAC-2 should not be lower than 150 °C and 165 °C, respectively. Then, the laboratory compaction work and on-site compaction work were calculated and converted based on the principle of energy equivalence. Consequently, the on-site compaction combination of rolling machines for four asphalt mixtures was determined. According to the volumetric parameters, the paving test section proved that the construction temperature and the on-site rolling combination determined by laboratory tests are reasonable, and ultra-thin overlay has good structural stability, drainage and skid resistance.

Involving local people in natural area management is very important to address the complexity of environmental management issues for sustainable use of local resources. Participatory methods require the contribution of local stakeholders in decision making. Mapping the environmental views of local communities allows for detecting aspects that could facilitate management efforts. This research – in the frame of the Skyros LIFE project and the PAMNATURA project - measures local acceptability of the conservation actions proposed by the LIFE project in Skyros Island (Greece) in relation with recording local people’s environmental orientation using the 15-item revised New Ecological Paradigm (NEP) scale. The research was carried out by means of questionnaires. The LIFE project proposed actions were grouped into three categories according to their theme, i.e. promoting (a) Nature protection, (b) Agro-pastoralism and (c) Ecotourism. The sample seems to largely agree with the LIFE project proposals, while the results showed high scores for most of the NEP scale items, implying pro-environmental beliefs, though there appears disagreement or neutrality regarding a few items. Local acceptability of the proposed actions was found to correlate to local people’s environmental concern measured through the NEP scale. Drawing on the results, implementation of actions related directly or indirectly to economic activities, preservation of traditional activities, as well as environmental education, interactive informing and consultation could enhance local participation. Skyros island seems to offer an appropriate social background for applying participatory and adaptive management and implementing conservation programs.

Background This paper draws learnings and successes based on field implementation experience spanning four years (2016–2019) of implementing CLTS by Prince of Peace Orphans and Widows Vision, a community-based organization located in Kaberamaido district in eastern Uganda. Methods The study aimed to document, disseminate and inform from an evidence-based point of view how adaptation and collaborative engagements triggers learning from mistakes to inform iterative changes from improvements and success.This is a descriptive paper that used project documents review based on field implementation experience. Existing project reports were synthesised, collated and curated for evidence. Data were drawn from project reports and records to inform narratives in writing. Implementation of the project was executed in homogenous rural communities occupied by people of the same dialect, cultural and social settings. Results We note that success in CLTS implementation can hardly be achieved by merely following prescriptions in handbooks and guidelines but rather by devising innovative community engagement and other participatory and community-driven techniques that foster adaptive management, promote ownership, and buy-in.Having learned from our failures, we used data to inform decisions and transformatively deviated from traditional CLTS implementation and introduced high impact and innovative approaches such as the use of CLTS helpdesks and Situation room, the Pamoja approach, learning labs and iterative feedback loops, innovatively tackling slippage and carefully introducing the follow-up mandona approach. These enhanced experiential learning and ultimately resulted in sustained sanitation behaviour. Conclusions The CLTS approach as outlined in the handbook needs to be flexibly adapted to address contextual needs. Reflective and learning sessions reinforced with routine feedback loops from implementers and beneficiaries yields tremendous results, propagates experiential learning, and ultimately results in a transformative deviation from undesirable to desired sanitation behaviours. These innovative approaches once carefully blended have proved to be sustainable, are adaptable and can work in an even larger scale and in a variety of contexts.

Eco-friendly and low-cost water-based nanolubricants containing rutile TiO2 nanoparticles (NPs) were developed for accelerating their applications in industrial-scale hot steel rolling. The lubrication performance of developed nanolubricants was evaluated in a 2-high Hille 100 experimental rolling mill at a rolling temperature of 850 ℃ in comparison to that of pure water. The results indicate that the use of nanolubricant enables to decrease the rolling force, reduce the surface roughness and the oxide scale thickness, and enhance the surface hardness. In particular, the nanolubricant consisting of 4 wt% TiO2, 10 wt% glycerol, 0.2 wt% sodium dodecyl benzene sulfonate (SDBS) and 1 wt% Snailcool exhibits the best lubrication performance by lowering the rolling force, surface roughness and oxide scale thickness up to 8.1%, 53.7% and 50%, respectively. The surface hardness is increased by 4.4%. The corresponding lubrication mechanisms are attributed to its superior wettability and thermal conductivity associated with the synergistic effect of rolling, mending and laminae forming that are contributed by TiO2 NPs.

Biological gels (bio-gels) are hydrated polymer networks that serve diverse biological functions, which often lead to intentional or unintentional exposure to particulate matter. In this work, we derive a microscopically motivated framework that enables the investigation of penetration mechanisms into bio-gels. We distinguish between two types of mechanisms: spontaneous (unforced) penetration and forced penetration. Using experimental data available in literature, we exploit the proposed model to characterize and compare between the micro-structures of respiratory, intestinal, and cervicovaginal mucus and two types of biofilms. Next, we investigate the forced penetration process of spherical and ellipsoidal particles into a locally quadrilateral network. The proposed framework can be used to improve and complement the analysis of experimental findings in vitro, ex vivo, and in vivo. Additionally, the insights from this work pave the way towards enhanced designs of nano-medicines and allow to assess risk factors related to the nano-pollutants exposure.

Severe postoperative pain affects most patients after thoracotomy and is a risk factor for post-thoracotomy pain syndrome (PTPS). This randomized controlled trial compared preemptively administered ketamine versus paravertebral block (PVB) versus control in patients undergoing posterolateral thoracotomy. The primary outcome was acute pain intensity on the visual analog scale (VAS) on the first postoperative day. Secondary outcomes included morphine consumption, patient satisfaction, and PTPS assessment with Neuropathic Pain Syndrome Inventory (NPSI). Acute pain intensity was significantly lower with PVB compared to other groups at four out of six time points. Patients in the PVB group used significantly less morphine via a patient-controlled analgesia pump than participants in other groups. Moreover, patients were more satisfied with postoperative pain management after PVB. PVB, but not ketamine, decreased PTPS intensity at 1, 3, and 6 months after posterolateral thoracotomy. Acute pain intensity at hour 8 and PTPS intensity at month 3 correlated positively with PTPS at month 6. Bodyweight was negatively associated with chronic pain at month 6. Thus, PVB but not preemptively administered ketamine decreases both acute and chronic pain intensity following posterolateral thoracotomies. The trial was prospectively registered at the Australian New Zealand Clinical Trial Registry (https://www.anzctr.org.au/; ACTRN12616000900415; 07 July 2016).

While deforestation rates decline globally they are rising in the Western Amazon. Artisanal-scale gold mining (ASGM) is a large cause of this deforestation and brings with it extensive environmental, social, governance, and public health impacts, including large carbon emissions and mercury pollution. Underlying ASGM is a broad network of factors that influence its growth, distribution, and practices such as poverty, flows of legal and illegal capital, conflicting governance, and global economic trends. Despite its central role in land use and land cover change in the Western Amazon and the severity of its social and environmental impacts, it is relatively poorly studied. While ASGM in Southeastern Peru has been quantified previously, doing so is difficult due to the heterogeneous nature of the resulting landscape. Using a novel approach to classify mining that relies on a fusion of CLASlite and the Global Forest Change dataset, two Landsat-based deforestation detection tools, we sought to quantify ASGM-caused deforestation in the period 1984–2017 in the southern Peruvian Amazon and examine trends in the geography, methods, and impacts of ASGM across that time. We identify nearly 100,000 ha of deforestation due to ASGM in the 34-year study period, an increase of 21% compared to previous estimates. Further, we find that 10% of that deforestation occurred in 2017, the highest annual amount of deforestation in the study period, with 53% occurring since 2011. Finally, we demonstrate that not all mining is created equal by examining key patterns and changes in ASGM activity and techniques through time and space. We discuss their connections with, and impacts on, socio-economic factors, such as land tenure, infrastructure, international markets, governance efforts, and social and environmental impacts.

Most of the pore-scale imaging and simulations of non-Newtonian fluid are based on the simplifying geometry of network modeling and overlook the fluid rheology and heat transfer. In the present paper, we developed a non-isothermal and non-Newtonian numerical model of the flow properties at pore-scale by direct simulation of the 3D micro-CT images using a Finite Volume Method (FVM). The numerical model is based on the resolution of the momentum and energy conservation equations. Owing to an adaptive meshing technique and appropriate boundary conditions, rock permeability and mobility are accurately computed. A temperature and concentration-dependent power-law viscosity model in line with the experimental measurement of the fluid rheology is adopted. The model is first applied at isothermal condition to 2 benchmark samples, namely Fontainebleau sandstone and Grosmont carbonate, and is found to be in good agreement with the Lattice Boltzmann method (LBM). Finally, at non-isothermal conditions, an effective mobility is introduced that enables to perform a numerical sensitivity study to fluid rheology, heat transfer, and operating conditions. While the mobility seems to evolve linearly with polymer concentration, the effect of the temperature seems negligible by comparison. However, a sharp contrast is found between carbonate and sandstone under the effect of a constant temperature gradient. Besides concerning the flow index and consistency factor, a good master curve is derived when normalizing the mobility for both the carbonate and the sandstone.

This paper delves into the strategic dimensions influencing the adoption of environmental innovations (EIs) in small and medium-sized manufacturing enterprises (SMEs) in Mexico City. Employing a mixed-methods approach combining documentary analysis and expert interviews, the study aims to provide a comprehensive understanding of integrating EI practices in the context of manufacturing SMEs. Qualitative methodology was chosen to explore experiences, perceptions, and practices related to EI adoption, acknowledging its ability to capture the complexity and richness of data. Through systematic literature review and semi-structured interviews with Corporate Social Responsibility experts, causal relationships and key factors influencing EI adoption were identified. The data analysis involved constructing causal maps and applying the Viable System Model to comprehend the interactions and dynamics within the organizational systems.

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of angiogenic therapies that treat diseases ranging from cardiovascular to cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20uM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases raging from wound healing to cancer.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

Besides the Lagrangian and the Eulerian descriptions, the motion of a body can also be expressed relative to the present configuration of the body, known as the relative motion description. It is interesting to consider such a relative motion description in general to formulate the basic system of field equations for solid bodies. In doing so, when the time increment from the present state is small enough, the nonlinear constitutive equations can be linearized relative to the present state so that the resulting system becomes linear. This will be done for thermoelastic materials with a brief comment on the exploitation of entropy principle in general. Relative Lagrangian formulation is based on the well-known ``small-on-large'' idea, and can be implemented for solving problems with large deformation in successive incremental manner. Some applications of such a formulation in numerical simulations are briefly reviewed.

Survey data from 42 Australian eastern seaboard veterinary practices involving 506 cases are reported with regard to clinical signs, disease severity, mortality, use of pharmaceuticals, and recovery times. New measures of disease severity (visual analogue scales (VAS) and facial expressions) were tested alongside “gold standard” measures (neuromuscular junction (NMJ) scores). Univariable and multivariable logistic regression analyses were conducted to evaluate associations between variables. The VAS scores were progressive, prognostic (especially the respiratory scores) and correlated with the NMJ scores. The presence of inspiratory dyspnoea and crackles on the day of hospitalization, progressing to expiratory dyspnoea and an expiratory wheeze 24 hours later were highly predictive of mortality. Altered facial features on hospital admission were also highly predictive of mortality. The previously used respiratory score (using various clinical signs) was not predictive of mortality. Older animals had a higher mortality rate and no gender or breed susceptibility was found. The only pharmaceuticals that were positively associated with mortality were tick anti-serum and, in severe cases, antibiotics. The use of many pharmaceutical products (acepromazine, atropine, steroids, antihistamines, antiemetics, diuretics and S8 anti-anxiety and sedation drugs) had no effect on mortality. More drug classes were used with increasing clinical severity and specific factors (e.g. vomiting/retching, hydration) affected the period of hospitalisation. Geographic variation in respiratory signs and toxicity scores was evident, whereas mortality and disease severity were not different across regions.

Small island developing states (SIDS) traditionally face a set of challenges like the narrow economic structure, environmental issues, and dependence on a few ranges of economic activities forcing them to open the economy to the exterior. Therefore, their development model, like in Cape Verde depends on migration, remittances, dependence on aid, tourism, and state employment. The current research offers an insight about the nature of Cape Verde’s economy as a SIDS and the degree to which its economy depends on tourism and government services, both of which are supported through aid programs. Understanding Cape Verde’s development model is important to clarify the challenges the country faces, and its development needs to gather a long-term resilience and to understand if it is changing from a MIRAB (Migrations, Remittances, Aid and Bureaucracy) model into another one.

Forest recreation can be successfully conducted for the purpose of psychological relaxation, as has been proven in previous scientific studies. During the winter in many countries, when snow cover occurs frequently, forest recreation (walking, relaxation, photography, etc.) is common. Nevertheless, whether forest therapy conducted in a forest environment with a snow cover will also have a positive effect on psychological indicators remains unknown. Furthermore, male subjects frequently participate in forest therapy experiments, whereas females are rarely involved. Thus, in this study, the effectuality of forest recreation during winter and with snow cover was tested on 32 young females. For these reasons, the experiment involved 15-minute periods of relaxation in a forest environment or in an urban environment, in addition to a pre-test under indoor conditions. Four psychological questionnaires (POMS, PANAS, ROS, SVS) were administered to participants before and after interventions. Results showed that participants’ levels of negative mood, as measured by different aspects of the POMS questionnaire (tension-anxiety, anger-hostility, depression-dejection, confusion, fatigue), decreased after exposure to the forest environment. In contrast, both tension-anxiety and anger-hostility increased in the urban environment. The indicator of negative affect from the PANAS questionnaire also increased after exposure to the urban environment, whereas the indicator of positive affect based on PANAS was higher in the forest environment than in the urban environment. Restorativeness and subjective vitality exhibited higher values after exposure to the forest environment in comparison to those from the control and pre-test. The changes in these indicators demonstrates that forest recreation in the snow during winter can significantly increase psychological relaxation in young females, as well as showing that recreation can be successfully conducted under these winter conditions.

There is a growing consensus that to effectively adapt to climate change, cities need user-friendly tools and reliable high-resolution biophysical and socio-economic data for analysis, mapping, modeling, and visualization. This study examines availability of various types of information used in climate adaptation plans of 40 municipalities with population less than 300,000 people in the United and in France, probing into the choice and usage of relevant information by small municipalities. We argue that non-climatic spatial data, such as population demographic and socio-economic patterns, urban infrastructure, and environmental data must be integrated with climate tools and datasets to inform effective vulnerability assessment and equitable climate adaptation planning goals. Climate adaptation plans frequently fail to address the existing structural inequalities and environmental injustices in urban infrastructure and land use. Adaptation methodological approaches should be reassessed in the context of much needed societal transformation. Lessons learned from our studies offer valuable insights for potential development of the national and state-level climate adaptation information services for cities.

Globally, the impact of COVID-19 on mental health has been significant. Pregnant women are known to be a vulnerable population in relation to mental health. In Australia, there was an unprecedented demand during the pandemic for mental health services, including services for pregnant women. Maternal mental health has unique and enduring features that can significantly shape a child’s overall development and poor maternal mental health can have considerable social and economic costs. This cross-sectional study evaluated antenatal depression and COVID-19 related distress in a sample of two hundred and sixty-nine pregnant women residing in Australia aged between 20 and 43 (M = 31.79, SD = 4.58), as part of a larger study. Social media advertising was used to recruit participants between September 2020 and November 2021. Prevalence rates for antenatal depression were found to be higher in this study (16.4%) compared with previous Australian prevalence rates (7%). COVID-19 distress in relation to having a baby during a COVID-19 outbreak significantly predicted antenatal depression, B = 1.46, p < .001. Results from this study suggest that mothers and families may have increased mental health vulnerabilities as a consequence of the pandemic for some time yet.

The electrocardiogram (ECG) was the first biomedical signal where digital signal processing techniques were extensively applied. By its own nature, the ECG is typically a sparse signal, composed of regular activations (the QRS complexes and other waveforms, like the P and T waves) and periods of inactivity (corresponding to isoelectric intervals, like the PQ or ST segments), plus noise and interferences. In this work, we describe an efficient method to construct an overcomplete and multi-scale dictionary for sparse ECG representation using waveforms recorded from real-world patients. Unlike most existing methods (which require multiple alternative iterations of the dictionary learning and sparse representation stages), the proposed approach learns the dictionary first, and then applies an efficient sparse inference algorithm to model the signal using the learnt dictionary. As a result, our method is much more efficient from a computational point of view than other existing methods, thus becoming amenable to deal with long recordings from multiple patients. Regarding the dictionary construction, we locate first all the QRS complexes in the training database, then we compute a single average waveform per patient, and finally we select the most representative waveforms (using a correlation-based approach) as the basic atoms that will be resampled to construct the multi-scale dictionary. Simulations on real-world records from Physionet's PTB database show the good performance of the proposed approach.

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

UN 2030 Sustainable Development Goal 6 presents difficulties for small island developing states such as the Kingdom of Tonga, which relies on rainwater and groundwater lenses for freshwater supply. Planning and managing water resources to supply demands in dispersed small islands under variable climate and frequent extreme events is challenging. Tensions between water planning using top-down versus bottom-up processes have long been recognized. Tonga’s overarching national planning instrument is the Tonga Strategic Development Framework, 2015-2025 (TSDFII). This identifies desired national outcomes and is used to direct and resource Ministries and address international and regional commitments. Water supply was a low priority in the three-month consultations that led to TSDFII. Community Development Plans (CDPs), developed by rural villages throughout Tonga’s five Island Groups over nine years, involved participation from 80% of each village population who ranked local priorities. Analysis of priorities in 117 available village CDPs reveals improvements to village water supply was the highest overall priority in all five Island Groups and ranked within the top three priorities by 76% of all villages, with women, youth and men returning figures of 83%, 66% and 80% respectively. The mismatch between top-down and bottom-up priorities appears to result from an urban/rural divide.

COVID-19 has rapidly spread worldwide since December 2019. During the pandemic, SARS-CoV-2 repeatedly mutated from Alpha to Omicron. The severity and mortality are related to age, sex, and underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, cancer, and immune diseases). We retrospectively studied 44 hospitalized stroke patients infected with the SARS-CoV-2 Omicron variant. The mortality rate of hospitalized stroke patients with COVID-19 was 6 (13.6%). The cause of death was coagulopathy in 3 cases of ischemic stroke. High modified Rankin Scale score（mRS）of stroke patient was correlated with severity of COVID-19. The timing of vaccination is inversely correlated with COVID-19 severity. In conclusion, stroke patients with COVID-19 have high mortality rates attributed to coagulopathy. Stroke patients with high mRS scores are more likely to develop severe COVID-19. In high mRS scores, therapy for severe COVID-19 should be administered.

Background: The potential impact of the pandemic on mental health should not be overlooked, especially among vulnerable populations such as women who gave birth during the COVID-19 pandemic. The aim of the study was to assess the mental health status of women who gave birth during a pandemic and to examine the possible links between the onset of depressive disorder symptoms in close proximity to the time of delivery and the socio-demographic conditions, health status and obstetric circumstances of the patients. Materials and Methods: The study is a cross-sectional survey conducted from 01.03.2020 to 01.03.2023, during the period of SARS-CoV-2 (COVID-19) pandemic, based on a retrospective evaluation of 860 postpartum women. The screening tool used to assess symptoms of postpartum depression was the Edinburgh Postnatal Depression Rating Scale (EPDS) questionnaire. The questionnaire was completed both in the Obstetrics and Gynaecology Clinical Sections I and II of the "Pius Brînzeu" County Emergency Hospital from Timisoara, Romania and online using Google Forms. Results: The highest severity of postpartum depression symptoms was observed during the COVID-19 pandemic. The results of the study conducted during the period of SARS-CoV-2 pandemic (COVID-19) showed that the prevalence of major postpartum depressive disorder (EPDS ≥ 13) was 54.2% (466 patients), while 15.6% (134) had minor depressive disorder (10 < EPDS ≤ 12) in the first year after delivery. Comparing these results with those obtained in research conducted before the onset of the pandemic period shows an alarming increase in the prevalence of postpartum depression. Risk factors associated with postpartum depression included type of delivery, level of education, socio-economic conditions, health status, age, background, personal obstetric history (number of abortions on demand, parity). Conclusions: The effects of the pandemic on mental health are of particular concern for women in the first year after childbirth. Observing these challenges and developing effective measures to prepare our health system early can help and facilitate effective mental health screening for postpartum women, promoting maternal and child health.

Large-scale farms are pivotal sites for the development of the agricultural industry, and the quality of the ecological environment is a significant factor affecting the growth of cereal crops. Consequently, assessing the ecological quality of large-scale farms is of great importance. This paper leverages the advantages of remote sensing imagery for long-term, quantitative, and dynamic monitoring of ecological quality over extensive areas. It develops an ecological assessment procedure suitable for agricultural regions based on an Improved Remote Sensing Ecological Index (IRSEI), which considers the coupling of ecosystem component elements. This procedure introduces a Pan-Salinity Index (PSI) tailored to the characteristics of soil salinization in farming areas and incorporates an ecological greenness index based on the Normalized Difference Vegetation Index (NDVI), an ecological humidity index derived from the K-T transform (WET), an ecological dryness index synthesized from the bare soil index and the built-up index (NDBSI), and an ecological heat index represented by the Land Surface Temperature (LST) calculated from atmospheric parameter models. These five indices are integrated into the ecological assessment system. The experimental results visually demonstrate the development and changes of ecological impact factors in the farm research area over the past decade, as well as the spatiotemporal variations in the quality of the farm's ecological environment. The findings indicate that between 2010 and 2019, the overall trend of IRSEI first declined, then rose, and subsequently experienced a slight decrease. Through differential analysis, regions and areas with declining ecological quality were identified, providing a data reference for the formulation and implementation of future ecological protection and management measures for the farm. The proposed IRSEI method offers a rapid and effective new monitoring approach for agricultural planting areas with a tendency towards soil salinization.

We investigate the behavior of the partial derivative approach to the change of scale formula and prove relationships among the analytic Wiener integral and the analytic Feynman integral of the partial derivative for the function space integral.

Ultra Low Temperature Process (ULTP) involve the material cooling in temperatures close to the liquid nitrogen (-196 °C), which is different from the cold-treatment (CT) made in temperatures close to -80 °C. ULTP treatments could raise the tool steel wear resistance through microstructural change that occurs on the material, enhancing, that way, the tools and dies lifetime. To investigate the impact on the wear resistance of tool steel AISI D2, micro abrasive wear tests were carried out and an analysis based on the Archard’s law was considered, evaluating specimen mass loss by laser interferometry. Micro hardness tests, X-ray diffractometry, scanning and optical microscopy and quantitative evaluation of carbides with image analysis were carried out aiming material characterization. Micro-scale abrasion tests shown a wear coefficient k about 1.73E-7 e 2.61E-7 mm3/N.mm to the specimens that received the ULTP phase and 3.12E-7 mm3/N.mm to the conventional thermal treatment, representing a wear resistance increase of 16.3 – 44.5% to cryogenically treated specimens. The results demonstrated a micro hardness improvement, ranging from 0.9 - 4.7% for the cryogenically treated specimens, when compared to the bulk material. This effect is related, mainly, to the retained austenite transformation in martensite and to the increase in the amount of fine secondary carbides dispersed in the martensitic matrixes of cryogenically treated specimens with ULTP. The best wear resistance improvements, on micro-scale, were achieved when the ULTP step is performed immediately after tempering.

The increasing use of energy resources recovered from the subsurface environments and the resulting carbon imbalance in the environment has motivated the need to develop thermodynamically downhill pathways to convert and store CO₂ as water insoluble calcium or magnesium carbonates. While previous studies extensively explored aqueous routes to produce calcium and magnesium carbonates from CO₂, there has been a limited scientific understanding of the phase evolution and textural changes during the direct gas-solid conversion routes to produce calcium carbonate from calcium hydroxide, which is one of the abundant constituents of alkaline industrial residues. With increasing interest in developing integrated pathways for capturing, converting and storing CO₂ from dilute flue gases, understanding the compositions of the product phases as they evolve is essential for evaluating the efficacy of a given processing route. Therefore, in this study, we investigate the phase evolution and the corresponding textural changes as calcium hydroxide is converted to calcium carbonate under the continuous flow of CO₂ at an ambient pressure of 1 atm and on heating continuously from 30 °C to 500 °C using in-operando wide angle X-ray scattering (WAXS), small angle X-ray scattering (SAXS), and ultra-small angle X-ray scattering (USAXS) measurements.

Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations, which generate a Premature Termination Codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ribosome’s capacity to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We investigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2’-O-methyltransferase.

As the global transition towards renewable energy accelerates, the integration of grid-scale energy storage systems has become increasingly critical for stabilizing energy supply and enhancing grid reliability. Among various storage technologies, lithium-ion batteries stand out for their high energy density, scalability, and relatively low environmental impact. This study investigates the performance and longevity of lithium-ion batteries in grid-scale applications, focusing on the impact of operational parameters such as cycling frequency, depth of discharge, temperature fluctuations, and charging/discharging rates. Employing a mixed-methods approach, we combined quantitative analysis of performance metrics (cycle life, capacity fade, efficiency) with qualitative assessments from case studies of existing grid-scale projects. Our findings reveal that while lithium-ion batteries exhibit robust performance in grid-scale storage, their longevity and efficiency are significantly influenced by operational conditions. Specifically, temperature management and optimized cycling strategies were identified as key factors in mitigating degradation and extending battery life. This research provides a comprehensive understanding of lithium-ion battery behavior in grid-scale environments, offering valuable insights for the design, optimization, and management of energy storage systems. By addressing the challenges of battery performance and longevity, our study contributes to the development of more sustainable and reliable grid storage solutions, facilitating the broader adoption of renewable energy sources.

Аnalysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that holds potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from both human and other species, including bacteria, fungi, and viruses, poses one of the most formidable challenges in the analysis of small RNA sequencing data, currently lacking satisfactory solutions. This study introduces sRNAflow, a user-friendly bioinformatic tool with a web interface designed for the analysis of small RNAs obtained from biological fluids. Tailored to the unique requirements of such samples, the proposed pipeline addresses various challenges, including filtering potential RNAs from reagents and environment, classifying small RNA types, managing small RNA annotation overlap, conducting differential expression assays, analysing isomiRs, and presenting an approach to identify the sources of small RNAs within samples. sRNAflow also encompasses an alternative alignment-free analysis of RNA-seq data, featuring clustering and initial RNA source identification using BLAST. This comprehensive approach facilitates meaningful comparisons of results between different analytical methods. The source code can be accessed at https://github.com/zajakin/sRNAflow under the GPL3 licence.

The residual content of the only carbon source increases at the end of the exponential growth phase when P. putida BS3701 cells are cultured under nitrogen deficiency. Moreover, the mRNA quantity of some genes involved in carbon catabolism decreases. There are no available data on regulators capable of stimulating the target mRNA degradation in pseudomonads under nitrogen deficiency in the literature. We have applied both comparative genomics methods and a number of biomolecular ones to identify new small P. putida BS3701 RNAs. This is due to the fact that the formation of ncRNA-mRNA duplexes, recognized by RNases, is one of the main mechanisms for reducing the number of transcripts in a cell. We have used the following selection criteria: 1) the presence of the interest gene of the NtrC binding site and a sigma54-dependent promoter in the upstream area, 2) the conservative location of the interest gene in the P. putida and P. aeruginosa genomes, 3) increase in the product quantity of the interest gene in a cell under nitrogen deficiency on two different carbon sources (succinate and naphthalene), 4) the product detection of the interest gene in a fraction enriched with small RNAs. The expression of two new small RNAs has increased twice or more times under nitrogen deficiency on both succinate and naphthalene: expression of ng171 and ng379. ng379 contains narK RNA motif.

The two-scale method (TSM) is an effective approach to simulate electromagnetic (EM) scattering from rough sea surface, to interpret physical interaction of EM wave with rough sea surfaces. The sea surface roughness spectrum and the cutoff wavenumber are two key factors affecting the accuracy of TSM simulation. This paper takes the geophysical model functions (GMFs) of different band as reference, and quantitatively studies the two factors based on the numerical simulation of different polarization backscattering coefficients. The numerical simulation demonstrates that Apel spectrum is more suitable for the backscattering simulation in C/X/Ku-band, and the optimal cutoff wavenumbers are also derived for TSM simulation of EM scattering in C/X/Ku-band. Then an empirical model function of optimal cutoff wavenumbers with respect to frequency, incident angle and wind speed are obtained with regression method. Finally, the simulation results with the new model function of cutoff wavenumber are compared with the GMF and measured data in different bands and they are all consistent. Moreover, a physical explanation for the optimal cutoff wavenumber is also given.

The local climate effects of utility-scale photovoltaic (PV) plants have also attracted more and more attention with the rapid development of PV industry. Turbulent fluxes and intensity characteristics for the PV plant and the adjacent reference site are investigated in the gobi area in Wujianqu in Xinjiang. Results indicate that near surface boundary layer is more unstable during the daytime while is more stable at the night in the PV plant than the reference site. The average roughness is 0.089m and 0.041m for the PV plant and the reference site respectively. The turbulence intensity in the vertical direction (I_w) of the PV plant is higher than the reference site especially during the daytime. The turbulent kinetic energy of the PV plant during the daytime is lower than the reference site.The momentum in the PV plant is higher than the reference site, especially during the daytime. Compared to the reference site, the PV plant has higher sensible heat flux and less latent heat flux. Site specific turbulent intensity relationships were developed for the PV plant and the reference site by analyzing wind components as a function of stability parameter (z/L). The turbulent components of wind followed 1/3 power law in the unstable conditions and stable conditions in the PV plant and the reference site.

Postpartum depression (PPD) has serious effects on maternal and infant morbidity and mortality. This study aimed to determine the prevalence of postpartum depression in mothers of under-twos in military barracks in Lagos. The Edinburgh Postnatal Depression Scale (EPDS) and a modified version of the General Help-Seeking questionnaire (GHSQ) were administered to 316 mothers of under-twos in 3 of 12 military barracks in Lagos, Nigeria to determine PPD and major depressive events (MDE). Risk of PPD was established at EPDS scores of >12. Good help-seeking practices were ascribed to scores of 20 or more on the GHSQ. Risk of PPD was found in 15.5% of respondents, and good help-seeking in 3.8% and 11.4% for personal/emotional and harming self/baby respectively. Bivariate analysis using Chi square showed statistically significant positive associations between lower scores for EPDS and higher educational levels of respondents, perception of partner support and being in lower wealth quintiles (p<0.05). Use of the EPDS was accepted among mothers of children aged under two years. Opportunities to educate pregnant women and new mothers about PPD using existing social networks, perinatal and infant screening programmes in the barracks can be leveraged upon to improve mental health delivery as part of maternity care.

This study investigated the removal characteristics of N-nitrosamines and their precursors at three pilot-scale water reclamation plants. These plants applies different integrated membrane systems: (1) microfiltration (MF) / nanofiltration (NF) / RO; (2) sand filtration/three-step RO; and (3) ultrafiltration (UF) / NF and UF / RO. Variable removal of N-nitrosodimethylamine (NDMA) by the RO membrane processes could be attributable to membrane fouling and feed water temperature. The effect of membrane fouling on N-nitrosamines removal was extensively evaluated at one of the plants by conducting one month of operation and chemical cleaning of the RO membrane element. Membrane fouling enhanced N-nitrosamines removal by the pilot-scale RO membrane process. This finding contributes to better understanding of variable removal of NDMA by RO membrane processes. This study also investigated the removal characteristics of N-nitrosamines precursors. The NF and RO membrane processes greatly reduced NDMA formation potential (FP), but the UF process had little effect. The contributions of MF, NF, and RO membrane processes for reducing FPs of NDMA, N-nitrosopyrrolidine (NPYR) and N-nitrosodiethylamine (NDEA) were different, suggesting different size distributions of their precursors.

The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

The study is aimed at developing a resilient benchmarking system for small hotels in Ukraine, designed to ensure their survival and growth amid global disruptions and local crises. Given the severe challenges associated with the COVID-19 pandemic and military actions, the resilience of the regional tourism business becomes particularly relevant. The methods used in the study, including factor and cluster analysis, the method of taxonomy, and dendrograms, have enabled the development of development programs for two clusters of hotels: those located in areas with increased military risk and those in relatively safe territories. The taxonomic analysis revealed significant differences in managerial practices and operational efficiency, largely determined by the geographic location of the hotels. Hotels in active combat zones experience a 40% reduction in tourist flow and financial instability, while hotels in safe areas demonstrate a 30% higher level of customer satisfaction. The application of advanced security systems and modern marketing techniques has led to a 40% reduction in incidents.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

Detecting rotational objects in remote sensing imagery is a significant challenge. These images typically encompass a broad field of view, featuring diverse and intricate backgrounds, with ground objects of various sizes densely scattered. As a result, identifying objects of interest within these images is a daunting task. While the integration of Convolutional Neural Networks (CNN) and Transformer networks leads to some advancements in rotational object detection, there is still room for improvement, particularly in enhancing the extraction and utilization of information related to smaller objects. To address this, our paper presents a multi-scale feature fusion module and a global feature context aggregation module. Initially, we fuse original, shallow, and deep features to reduce the loss of shallow feature information, thereby improving the detection performance of small objects in complex backgrounds. Subsequently, we compute the correlation of contextual information within feature maps to extract valuable insights. We name the newly proposed model the "Multiscale Feature Context Aggregation Module" (MFCA). We evaluate our proposed methodology on three challenging remote sensing datasets: DIOR-R, HRSC, and MAR20. Comprehensive experimental results show that our approach surpasses baseline models by 2.07\% mAP, 1.02\% mAP, and 1.98\% mAP on the DIOR-R, HRSC2016, and MAR20 datasets, respectively.

The images captured by UAVs during inspection often contain numerous small targets related to transmission lines, which are critical and vulnerable elements for ensuring the safe operation of these lines. However, due to various factors such as the small size of the targets, low resolution, complex background, and potential line aggregation, achieving accurate and real-time detection becomes challenging. To address these issues, this paper proposes a detection algorithm called P2-ECA-EIOU-YOLOv5 (P2E-YOLOv5). Firstly, in order to address the challenges posed by the complex background and environmental interference that impact small targets, an ECA attention module is integrated into the network. This module effectively enhances the network's focus on small targets while concurrently mitigating the influence of environmental interference. Secondly, considering the characteristics of small target size and low resolution, a new high-resolution detection head is introduced, which is more sensitive to small targets. Lastly, the network utilizes the EIOU-Loss as the regression Loss function to improve the positioning accuracy of small targets, as they tend to aggregate. Experimental results demonstrate that the proposed P2E-YOLOv5 detection algorithm achieves an accuracy P of 96.0% and an average accuracy (mAP) of 97.0% for small target detection in transmission lines.

Infrared detection plays an important role in the military, aerospace, and other fields, which has the advantages of all-weather, high stealth, and strong anti-interference. However, infrared dim small target detection suffers from complex backgrounds, low signal-to-noise ratio, blurred targets with small area percentages, and other challenges. In this paper, we proposed a multiscale YOLOv5-AFAM algorithm to realize high-accuracy and real-time detection. Aiming at the problem of target intra-class feature difference and inter-class feature similarity, the Adaptive Fusion Attention Module - AFAM was proposed to generate feature maps that are calculated to weigh the features in the network and make the network focus on small targets. This paper proposed a multiscale fusion structure to solve the problem of small and variable detection scales in infrared vehicle targets. In addition, the downsampling layer is improved by combining Maxpool and convolutional downsampling to reduce the number of model parameters and retain the texture information. For multiple scenarios, we constructed an infrared dim and small vehicle target detection dataset, ISVD. The multiscale YOLOv5-AFAM was conducted on the ISVD dataset, compared to YOLOv7, [email protected] achieves a small improvement while the parameters are only 17.98% of it. By contrast with the YOLOv5s model, [email protected] was improved by 4.3% with a 6.6% reduction in the parameters. Experiments results demonstrate that the multiscale YOLOv5-AFAM has a higher detection accuracy and detection speed on infrared dim and small vehicles.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Human cytomegalovirus (HCMV) is a leading cause of severe diseases in immunocompromised individuals, including AIDS and transplanted patients, and in congenitally infected newborns. The utility of available drugs is limited by poor bioavailability, toxicity, and emergence of resistant strains. Therefore, it is crucial to identify new targets of therapeutic intervention. Among the latter, viral protein-protein interactions are becoming increasingly attractive. Since dimerization of HCMV DNA polymerase processivity factor ppUL44 plays an essential role in the viral life cycle being required for oriLyt-dependent DNA replication, we performed an in silico screening and selected 18 small molecules (SMs) potentially interfering with ppUL44 homodimerization. Antiviral assays using recombinant HCMV TB40-UL83-YFP in the presence of the selected SMs led to the identification of four active compounds. The most active one, B3, also efficiently inhibited AD169 in plaque reduction assays and impaired replication of an AD169-GFP reporter virus and its ganciclovir-resistant counterpart to a similar extent. As assessed by Western blotting experiments, treatment of infected cells with B3 specifically reduced viral gene expression starting from 48 h post infection, consistent with activity on viral DNA synthesis. Therefore, inhibition of ppUL44 dimerization could represent a new class of HCMV inhibitors, complementary to those targeting the DNA polymerase catalytic subunit or the viral terminase complex.

Importance: The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation: We present expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, and attenuate the immunocompromising effects of lung cancer therapies. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance: The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

Small non-coding RNAs (sRNAs) are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing, and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting), are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3’ UTR, 5’ UTR, CDS-binding). These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting). While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved, and how sRNAs integrate with complex regulatory networks.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

Airworthiness certification requires proof of structure strength, which is performed generally through building block approach. To achieve this, representative intermediate scale experiments generated by test benches are in general needed, additionally to material characterization at coupons scale and structure testing at large scale. The VERTEX test bench can generate combined loading of tension/compression-shear-pressure on structural elements and was modelled with Finite Elements to perform virtual testing representative of its intermediate-scale specificity. The numerous bolted joints of the bench were modelled and their behavior identified in previous tests, so the model could quantitatively estimate the transfer function of the bench, which is the relation between the displacements imposed by the jacks and the resulting loads on a given sample. The VERTEX model was identified to represent load shapes and amplitudes on a training set, and was later confronted to a validation set of tests of tension and shear. A model with ideal boundary conditions was also developed for comparison but it failed to predict some load shape specificities and did not give any indication of loading amplitude. Application cases of the developed model are shown to assess a range of virtual testing possibilities.

The study purpose was to train and validate a deep-learning approach to detect micro-scale streetscape features related to pedestrian physical activity. This work innovates by combining computer vision techniques with Google Street View (GSV) images to overcome impediments to conducting audits (e.g., time, safety, and expert labor cost). The EfficientNETB5 architecture was used to build deep-learning models for eight micro-scale features guided by the Microscale Audit of Pedestrian Streetscapes-Mini tool: sidewalks, sidewalk buffers, curb cuts, zebra and line crosswalks, walk signals, bike symbols, and streetlights. We used a train--correct loop, whereby images were trained on a training dataset, evaluated using a separate validation dataset, and trained further until acceptable performance metrics were achieved. Further, we used trained models to audit participant (N=512) neighborhoods in the WalkIT Arizona trial. Correlations were explored between micro-scale features and GIS-measured- and participant reported-macro-scale walkability. Classifier precision, recall, and overall accuracy were all >84%. Total micro-scale was associated with overall macro-scale walkability (r=0.300,p<.001). Positive associations were found between model-detected and self-reported sidewalks (r=0.41,p<.001) and sidewalk buffers (r=0.26,p<.001). Computer vision model results suggest an alternative to trained human raters, allowing for audits of hundreds or thousands of neighborhoods for population surveillance or hypothesis testing.

Turbulent flows over and within forest canopies have recently been modeled with success using Large Eddy Simulations (LES). Validation exercises against experimental data suggest that models can be applied with a high degree of confidence for many applications, mechanical and physiological plant/atmosphere interaction analysis, seed or pollen dispersal, wildfire spread and firebrand transport, or investigation of causes of eddy-covariance technique bias. Long distances required for shear-induced turbulence to equilibrate, result in the widespread use of cyclic boundary conditions in LES atmospheric boundary layer studies. Vegetation drag dissipates air momentum in the atmosphere, but equilibrium is often achieved through compensatory momentum source, supplied by macro-scale pressure gradient forcing. Unfortunately, both classical Ekman balance or simple spatially-constant pressure gradient techniques for implementing this forcing have major drawbacks in the context of cyclic boundary conditions for the applications listed above. Among them, it is difficult to specify aspects of the mean velocity profile such as a specific desired wind velocity and direction at a reference height. In the present paper, we propose a new technique for capturing the effects of a large-scale pressure gradient force (LSPGF) that can be used at stand scale and enables simulation of realistic and specifiable wind fields. Several variants of this LSPGF are developed and analyzed here and validated against experimental data. Although this LSPGF technique is developed in the context of HIGRAD/FIRETEC wildfire simulations, LSPGF can be used for any LES wind modeling application aimed at generating detailed stand-scale wind fields with resolved turbulence and shear profiles consistent with vegetation structure in the boundary layer.

The ecological background condition of the semi-arid steppe region (SASR) is extremely fragile. It is recognized that the development of coal and electricity power is a kind of strong human interference behavior for regional landscape ecology. Landscape ecological classification (LEC) is the premise of landscape ecology research of the mining area. The current research on the SASR and grassland LEC of coal-power base is relatively less, but still remains uncertainty concerning how to stratify and classify urban mining landscapes into units of ecological significance at spatial scales appropriate for management. This study is based on hierarchy theory, scale theory, landscape process, the patch-corridor-matrix model, the network, the theory of multiple planning integration and the principle of remote sensing. According to the comprehensive principle, principles of the combining of structure and function, principle of the combining human-ominated and natural landscape, principle of emphasis, and principle of combining qualitative analysis with quantitative research of LEC in large-scale coal-power base(LSCPB). On the basis of occurrence method land classification, fully consider the ecological attributes of the land, integration pattern, processes and function theory of the landscape ecology, the LEC system of the LSCPB in the SASR has been constructed by using top-down decomposition classification method. Empirical research of the Victory and Mindong No.1 mining areas of Shenhua Group shows that the classification system constructed in this paper can meet the requirements of LEC and fully reflect the status of landscape ecology of LSCPB in SASR. This study can provide theoretical guidance for the landscape ecology of LSCPB, while also supporting a theoretical reference for the LEC research.

Urban wind energy has emerged as an attractive source of distributed generation in cities to achieve sustainable development goals. The advance in technologies for the use of urban wind energy has turned this source into an attractive alternative for the decarbonization of cities and the energy transition. The objectives of this work are (1) to identify the potential of wind energy through numerical weather prediction (NWP) data tools and (2) to identify the roles and responsibilities of the stakeholders involved in the decision-making process. A methodology was developed in two phases and applied to a case study in the Dominican Republic. The first phase consisted of estimating the wind energy potential for the 32 provinces at a height of 10 m using open-access geographic reference systems tools provided by NASA. In the second phase, 28 stakeholders were identified through snowball sampling. The Responsible, Accountable, Consult, and Informed (RACI) matrix tool was applied to identify the roles of the 28 institutions addressed at the country level as relevant in the decision-making process for the energy sector. The annual average wind speed and energy potential for each province were determined. It was found 24 provinces have poor potential, below &lt;4.5 m/s. In the northwest and east is where there is the greatest potential, between 4.83 - 6.63 m/s. The population density was established and was observed that the provinces with greater potential are less densely populated. Through 59 interviews 28 institutions were identified and evaluated due to their relevance in decision-making for the implementation of energy projects. The MEM has strongly categorized as “A”, electricity distribution companies as “R”, energy associations and universities as “C”, and educational and justice institutions as “I”.

Abstract Kidney transplant recipients, because of a weak immune response due to the assumption of immunosuppressant are exposed to the risk of COVID-19 infection. This fact realize the problem on how to treat the severe infection without carrying the risk of acute rejection due to the reduction of the immunosuppressive drugs. The best are the prophylactic measures to be taken before transplantation as vaccination. If the patient is already transplanted, three measures may be undertaken: Vaccination, use of monoclonal antibodies, use of therapeutic antiviral small molecules. Concerning vaccination is still debated which one is the best and how many doses should be given. The surge of new virus variant is the major problem and invites to find new active vaccines. In addition, not all the transplanted patients develop antibodies. The other measure is the use of monoclonal antibodies. They may be used as prophylaxis or in the early stage of the disease. Finally, the antiviral small molecules may be used again as prophylaxis or treatment. Their major drawback are the interference with the immunosuppressive drugs and the fact that some of them cannot be administered to patients with low eGFR.

Unification point of view, quantum cosmology must be given a priority and one should make a note that, Spin is a basic property of quantum physics and rotation is a very common experience. In this context, we have developed a quantum model of cosmology associated with Machian universe having Planck scale origin, total dark matter, light speed rotation and equality of gravitational self energy density and thermal energy density. We would like to appeal that, observed cosmic radius and age seem to be shortened by 146.3 times their actual magnitudes.

As gravitation and electromagnetism are closely analogous long-range interactions, and gravitation is formulated in terms of geometry in general relativity (GR), we expect the latter also to appear through the geometry. This unification has however remained an unfulfilled goal. The goal is achieved here in a new theory, which results from the principles of equivalence and Mach supplemented with a novel insight that the field tensors in a geometric theory of gravitation and electromagnetism must be traceless, since these long-range interactions are mediated by virtual exchange of massless particles whose mass is expected to be related to the trace of the field tensors. Hence the Riemann tensor, like the analogous electromagnetic field tensor, must be traceless. Thence emerges a scale- invariant, Machian theory of gravitation and electrodynamics unified, wherein the vanishing of the Ricci tensor appears as a boundary condition. While the field equations of the theory are given by the vanishing divergence of the respective field tensors and their duals, the matter and charge emerge from the spacetime. A quantitative formulation of the emergent fields embodied in ‘energymomentum super tensors’ follows from the respective Bianchi identities for the two fields. The resulting theory is valid at all scales and explains the observations without invoking the non-baryonic dark matter, dark energy or inflation. Moreover, it answers the questions that the GR-based standard paradigm could not address.

The open-bundle structure of cytochrome c’ as an unfolding intermediate was determined by small-angle neutron scattering experiment (SANS). The four-α-helix bundle structure of Cyt c’ at neutral pH was transited to an open-bundle structure (at pD ~13), which is a joint-clubs consisting of four clubs (α-helices) connected by short loops. The compactly folded structure of Cyt c’ (radius of gyration, Rg = 18 Å for the Cyt c’ dimer) at neutral or mildly alkaline pD transitioned to a remarkably larger “open-bundle” structure at pD ~13 (Rg = 25 Å for the Cyt c’ monomer). Cyt c’ adopts an unstructured random coil structure at pD = 1.7 (Rg = 25 Å for the Cyt c’ monomer). Numerical partial scattering function analysis (joint-clubs) and ab initio modelling gave structures similar to the “open-bundle”, which retains the α-helices but loses the bundle structure.

The conversion of native habitats into anthropogenic ones compromises the original composition and configuration of the landscapes, influencing ecological dynamics and affecting biodiversity. Increasingly, landscape ecology has shown that these effects can only be understood if accessed at adequate spatial scales, as the scale which landscape structure is evaluated influences species responses. Here, we investigated how three variables of landscape composition (proportion of forest, coffee crop and pasture) and two of configuration (number of fragments and mean nearest neighbor distance) interfere in the richness and composition of medium and large-sized mammals considering a multiscale approach. We recorded medium and large-sized mammal species in 13 landscapes with predominantly matrices of coffee and pasture in Minas Gerais, Brazil. Then, we built distance-based linear models to identify the scale of effect of each landscape variable for both response variables considering eight scales (from 250 m to 2000 m). Finally, we verified the influence of the landscape on the richness and composition of mammals, considering the landscape variables in their respective scales of effect. We found 67% of the probable species occurring in the region. The scales of effect varied among landscape variables probably due to the different variables affect different aspects of organisms' ecological requirements. The proportion of pasture in the landscape explained the variation in species richness, while the proportion of forest explained the variation in species composition. In addition, the proportion of pasture in the landscape had a positive influence on species richness, indicating that this matrix may favor the presence of generalist species of habitat and/or this result is due to the higher concentration of species in the fragments immersed in this matrix. These results suggest that considering different responses to biodiversity is important to understand different aspects of the landscape's influence on biodiversity. In addition, the composition of the landscape is fundamental for the perpetuation of species and, therefore, both forest cover and types of matrices in the landscape must be considered to improve species conservation strategies. Finally, generalizing a spatial scale can lead to misinterpretations about the influence of the landscape on biodiversity.

Dynamic crossflow filtration (DCF) is the state-of-the-art technology for solid-liquid separation from viscous and sensitive feed streams in the food and biopharma industry. Up to now, the potential of industrial processes is often not fully exploited because fixed recipes are usually applied to run the processes. Therefore, a digital twin has been developed to optimize an industrial brownfield DCF plant. The core of the digital twin is a mechanistic-empirical process model combining fundamental filtration laws with process expert knowledge. The effect of variation of selected process and model parameters on plant productivity has been assessed using a model-based design-of-experiments approach and a regression metamodel has been trained with the data. A cyclic program that bidirectionally communicates with the DCF asset serves as frame of the digital twin. It monitors the process dynamics membrane torque and transmembrane pressure and feeds back the optimum permeate flow rate setpoint to the physical asset in almost real-time during process runs. The presented digital twin framework is a simple example how an industrial established process can be controlled by a hybrid model-based algorithm. With a digital process dynamics model at hand, the presented metamodel optimization approach can be easily transferred to other (bio)chemical processes.

In this study, the distribution patterns of southern horse mackerel are examined using commercial fine-scale resolution data. Using landings by size category and VMS data from the Portuguese commercial bottom trawl fishery, which consistently targets horse mackerel, this study provides a comprehensive analysis of horse mackerel age distributions spanning a decade (2010-2020). Importantly, the study addresses potential biases in commercial effort data and establishes the usefulness of commercial bottom-trawl gear as a suitable method for sampling and evaluate southern horse mackerel stock dynamics. Ordered regression models were applied to allow for the modelling of the distribution of multiple age categories and investigate spatio-temporal migrations off the Portuguese coast. Southern horse mackerel shows a widespread age distribution range and stable abundance with indications of seasonal and spatial patterns in the distribution of specific age groups. The insights derived from this research contribute valuable knowledge for understanding the dynamics and distribution patterns of fish populations.

Deep networks-based hashing has gained significant popularity in recent years, particularly in the field of image retrieval. However, most existing methods only focus on extracting semantic information from the final layer, disregarding valuable structural information that contains important semantic details crucial for effective hash learning. To address this limitation and improve image retrieval accuracy, we propose a novel deep hashing method called Deep Supervised Hashing by Fusing Multiscale Deep Features (DSHFMDF). Our approach involves extracting multiscale features from multiple convolutional layers and fusing them to generate more robust representations for efficient image retrieval. Experimental results on CIFAR10 and NUS-WIDE datasets demonstrate that our method surpasses the performance of state-of-the-art hashing techniques.

To address the challenges of climate change and food security, the establishment of smart farm complexes is necessary. While there have been numerous studies on the productivity and environmental control of individual greenhouses, research on greenhouse complexes is considerably limited. Conducting environmental studies during the design phase of these complexes poses financial constraints and practical limitations in terms of on-site experiments. To identify potential issues that may arise when developing large-scale greenhouse complexes, it is possible to utilize modeling techniques using Computational Fluid Dynamics (CFD) to assess environmental concerns and location issues before constructing the facilities. Consequently, simulating large-scale CFD models that incorporate multiple greenhouses and atmospheric conditions simultaneously presents significant numerical challenges. The objective of this study was to develop a guideline for verifying CFD models for a large-scale Venlo greenhouse, where acquiring field data before construction is not feasible for designing a greenhouse complex. The verification processes of the CFD models were conducted using 2D and 3D iterative simulations of a 2-hectare greenhouse model, using the improved Grid Independence Test (GIT) and wall Y+ approaches. Subsequently, the aerodynamic characteristics were analyzed in a 3D greenhouse model to access its performance when the wind direction was 90° in summer season. The findings revealed that a grid resolution of 0.8 meters and a first layer height of 0.04 meters were suitable for developing large-scale greenhouse models, resulting in a low Root Mean Square Error (RMSE) of 3.9% and a high coefficient of determination (R2) of 0.968. This process led to a significant reduction of 38% in the number of grid cells. These results will serve as design standards for large-scale greenhouses.

When undertaking wind assessment around buildings using large eddy simulation (LES), the implementation of the integral length scale at the inlet for inflow generation is controversial, as real atmospheric length scales require huge computational domains. While length scales significantly influence inflow generation in the domain, their effect on the downstream flow field has not yet, been investigated. In this paper, we validate the effectiveness and accuracy of implementing a reduced turbulence integral length scale for inflow generation in LES results at the rooftop of low-rise buildings and develop a technique to estimate the real local length scales using simulation results. We measure the wind locally and calculate the turbulence length scales from the energy spectrum of the wind data and simulation data. According to these results, there is an excellent agreement between the length scale from simulation and measurement when they are scaled with their corresponding freestream/inlet value. These results indicate that a reduced integral length scale can be safely used for LES to provide a reliable prediction of the energy spectrum as well as the length scales around complex geometries. The simulation results were confidently employed to obtain the best location for a wind turbine installation on low-rise buildings.

Cerebrovascular and airway structures are tubular structures used for transporting blood and gases, respectively, providing essential support for the normal activities of the human body. Accurately segmenting these tubular structures is the basis of morphology research and patho-logical detection. Nevertheless, accurately segmenting these structures from images presents great challenges due to their complex morphological and topological characteristics. To address this challenge, this paper proposes a framework UARAI based on the U-Net multi-scale reverse at-tention network and sparse convolution network. The framework utilizes a multi-scale structure to effectively extract the global and deep detail features of vessels and airways. Further, it enhances the extraction ability of fine-edge features by a joint reverse attention module. In addition, the sparse convolution structure is introduced to improve the features' expression ability without increasing the model's complexity. Finally, the proposed training sample cropping strategy re-duces the influence of block boundaries on the accuracy of tubular structure segmentation. The experimental findings demonstrate that the UARAI-based metrics, namely Dice and IoU, achieve impressive scores of 90.31% and 82.33% for cerebrovascular segmentation and 93.34% and 87.51% for airway segmentation, respectively. Compared to commonly employed segmentation tech-niques, the proposed method exhibits remarkable accuracy and robustness in delineating tubular structures such as cerebrovascular and airway. These results hold significant promise in facilitating medical image analysis and clinical diagnosis, offering invaluable support to healthcare profes-sionals.

We present a new family of Bessel solutions of the paraxial equation. Such solutions keep their form during propagation due to a quadratic phase factor that makes them scaled propagation invariant fields. The Bessel beams we introduce have the particularity that the topological phase is twice the order of the Bessel function and the argument varies quadratically with the radius

The temporal evolution of pandemics described by the susceptible-infectious-recovered (SIR)-compartment model is sensitively determined by the time dependence of the infection (a(t)) and recovery (u(t)) rates regulating the transitions from the susceptible to the infected and from the infected to the recovered compartment, respectively. Here approximated SIR-solutions for different time dependencies of the infection and recovery rates are derived which are based on the adiabatic approximation assuming time-dependent ratios k(t)=u(t)/a(t) varying slowly in comparison to the typical time characteristics of the pandemic wave. For such slow variations the available analytical approximations from the KSSIR-model, valid for a stationary value of the ratio k, are used to insert a-posteriori the adopted time-dependent ratio of the two rates. Instead of investigating endless different combinations of the time dependencies of the two rates a(t) and u(t) a suitably parameterized reduced time dependence of the ratio k(tau) is adopted. Together with the definition of the reduced time this parameterized ratio k(tau) allows us to cover a great variety of different time dependencies of the infection and recovery rates. The agreement between the solutions from the adiabatic approximation in its four different studied variants and the exact numerical solutions of the SIR-equations is remarkably good providing strong confidence in the accuracy of the proposed adiabatic approximation.

The late universe contains a wealth of information about fundamental physics and gravity, wrapped up in non-Gaussian fields. To make use of as much information as possible it is necessary to go beyond two-point statistics. Rather than going to higher order N-point correlation functions, we demonstrate that the probability distribution function (PDF) of spheres in the matter field (a one-point function) already contains a significant amount of this non-Gaussian information. The matter PDF dissects different density environments which are lumped together in two-point statistics, making it particularly useful for probing modifications of gravity or expansion history. Our approach in Cataneo et. al. 2021 extends the success of Large Deviation Theory for predicting the matter PDF in ΛCDM in these “extended” cosmologies. A Fisher forecast demonstrates the information content in the matter PDF via constraints for a Euclid-like survey volume combining the 3D matter PDF with the 3D matter power spectrum. Adding the matter PDF halves the uncertainties on parameters in an evolving dark energy model, relative to the power spectrum alone. Additionally, the matter PDF contains enough non-linear information to substantially increase the detection significance of departures from General Relativity, with improvements up to six times the power spectrum alone. This analysis demonstrates that the matter PDF is a promising non-Gaussian statistic for extracting cosmological information, particularly for beyond ΛCDM models.

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100nm) can be used in the treatment of cancer owing to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nano-formulations have created brand new perspectives for cancer treatment. However, a majority of the research is limited to in vivo and in vitro studies, and the number of nano-drugs that are approved has not much amplified over the years. In this review, we discuss numerous types of nanoparticles, targeting mechanisms along with approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

Complex systems can be described as the network of interactions between their components. In directed networks, information, energy and matter flow in dominant directions. Undirected networks, on the other hand, cannot easily capture these asymmetries. The local flow of information depends on the node spin, which is a function of the number of incoming and outgoing links attached to it. And yet, how the heterogeneous association between in-degree and out-degree constraints global dynamics remains poorly understood. Here, we develop a new theoretical model to study the relationship between node directionality and global flow dynamics. Our computational analysis of random and scale-free directed networks indicates that structural diversity constrains the dimensionality of reachable dynamical space. These results suggest how local directionality might be an universal driver of global dynamics in many systems, from social networks, to technological systems to the connectome.

Therapeutic proteins are used to successfully treat hemophilia, Crohn’s Disease, diabetes, and cancer. Recent product recalls have occurred because of sub-visible particle formation resulting from the inherent instability of proteins. It has been suggested that particle formation is associated with late stage processing steps of filling, shipping, and delivery. Previous works demonstrated that cavitation might occur in therapeutic vials subjected to agitation or accidentally dropped, but that mitigation can be achieved with fluid property manipulation. The goal of this research was to (1) assess the risk of cavitation under common pharmaceutical manufacturing conditions (i.e., pipe contraction and pumps), (2) establish a simple threshold criterion for when particulate will form, and (3) suggest a series of mitigation techniques based on these thresholds. To accomplish these tasks, computational fluid dynamic simulations for a variety of pipe contraction and fluid properties were performed. The results of this research show that reducing the turbulence in a fluid system will reduce the likelihood of cavitation. Additionally, threshold bounds were created that establish a definitive transition at which cavitation will occur.

The technique of Faraday tomography is a key tool for the study of magnetised plasmas in the new era of broadband radio polarisation observations. In particular, observations at metre-wavelengths provide significantly better Faraday depth accuracies compared to traditional cm-wavelength observations. However, the effect of Faraday depolarisation makes the polarised signal very challenging to detect at metre wavelengths (MHz frequencies). In this work, Faraday tomography is used to characterise the Faraday rotation properties of polarised sources found in data from the LOFAR Two-Metre Sky Survey (LoTSS). Of the 76 extragalactic polarised sources analysed here, we find that all host a radio-loud AGN. The majority of the sources (∼64%) are large FRII radio galaxies with a median projected linear size of 710 kpc and median radio luminosity at 144 MHz of 4 × 10^26 W/Hz. In several cases, both hotspots are detected in polarisation at an angular resolution of ∼20". One such case allowed a study of intergalactic magnetic fields on scales of 3.4 Mpc. Other detected source types include an FRI radio galaxy and at least 8 blazars. Most sources display simple Faraday spectra, however, we highlight one blazar that displays a complex Faraday spectrum, with two close peaks in the Faraday dispersion function.

Given the cross-scale interactions of agricultural ecosystems, it is important to collect ecosystem service data at the multiple spatial scales they operate at. Mapping of ecosystem services helps to assess their spatial and temporal distribution and is a popular communication tool of their availability and value. For example, maps can be used to quantify distance between areas of available ecosystem services and their beneficiaries and how services fluctuate with changes in land use patterns over time, allowing identification of synergies and trade-offs. However, a lack of local context and too large a resolution can reduce the utility of these maps, whilst masking heterogeneities in access due to equity dynamics. This review identifies and summarizes eight main methods of ESS mapping found in the literature—remote sensing, biophysical modelling, agent based modelling, economic valuation, expert opinion, user preference, participatory mapping, and photo-elicitation. We consider what spatial scales these methods are utilized at and the transferability of data created by each method. The analysis concludes with a methodological framework for mapping ecosystem services, intended to help researchers identify appropriate methods for a multi-scale research design. The framework is exemplified with an overview of a research project in Ethiopia.

This paper evaluates the feasibility of applying Massive MIMO to tackle the uplink mixed-service communication problem. Under the assumption of an available physical narrowband shared channel (PNSCH), devised to exclusively consume data traffic from Machine Type Communications (MTC) devices, the capacity (i:e:, number of connected devices) of MTC networks and, in turn, that of the whole system, can be increased by clustering such devices and letting each cluster share the same time-frequency physical resource blocks. Following this research line, we study the possibility of employing sub-optimal linear detectors to the problem and present a simple and practical channel estimator that works without previous knowledge of the large-scale channel coefficients. Our simulation results suggest that the proposed channel estimator performs asymptotically as well as the MMSE estimator with respect to the number of antennas and the uplink transmission power. Furthermore, the results also indicate that, as the number of antennas is made progressively larger, the performance of sub-optimal linear detection methods approaches the perfect interference-cancellation bound. The findings presented in this paper shed light on and motivate for new and exciting research lines towards a better understanding of the use of massive MIMO in MTC networks.

In recent years, the emergence of spatiotemporal big data has made the transition of functional identification from the physical dimension to socioeconomic or human activities becoming more common. In the identification of urban functional areas, most studies considered only a single data source and a single division scale, the research results have problems such as low update frequency or incomplete information in a single data set, and overfitting or underfitting in a single spatial resolution. Using taxi trajectory data and point of interest (POI) data as the main data source, this study proposes a multi-scale recursive identification method for urban functional areas based on cross-validation. First, used the dynamic time warping (DTW) algorithm generates a time series similarity matrix, the CA-RFM model combines the clustering algorithm and random forest model is constructed, the model uses a clustering algorithm (K-MEDOIDS) to extract sig-nificant feature regions as input, which are imported into the random forest model for UFZ identification. Then, to overcome the shortcomings of single scale in expressing urban structural characteristics, a recursive model of different levels of urban road networks is established to classify multi-scale functional areas. Finally, cross-validation using the CA-RFM model and POI quantitative identification method, obtains the final identification results of urban functional areas. This paper selects Shenzhen as the study area for the case study, the results show that the com-bination of clustering algorithm and random forest model greatly reduces the error of manual selection of training samples. In addition, the research shows the superiority of the multi-scale recursive identification method that fuses multi-source data and performs cross-validation from two aspects, that is, the division speed of urban functional area identification results is accelerated and the accuracy is improved.

Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.

Background: Social Anxiety Disorder (SAD) is among the most common anxiety disorders worldwide with data largely emerging from the Euro-American and Pacific Rim populations. In contrast, there is a dearth of studies among the populations of Arabian Gulf countries including Oman. This study has two interrelated aims: (i) to explore the prevalence of SAD among Omani adults, and (ii) to tease out the links between sociodemographic factors and SAD in Oman. Methods: A cross-sectional study via an online survey was conducted among 1019 adult Omani nationals residing in Oman. The presence of SAD was assessed using the Arabic version of the Liebowitz Social Anxiety Scale (LSAS). Result: Nearly half the participants (45.9%, n=468) endorsed themselves as having features of SAD as defined by LSAS. In the multivariate logistic analysis, participants below 40 years of age were 1.6 times (OR=1.568, p=0.026) more likely to have SAD than those who were 40 and older. Women were 1.3 times (OR=1.348, p=0.038) more likely to endorse SAD than men. Participants who had secondary or undergraduate education were respectively 1.5 times (OR=1.45, p=0.014) and 2.5 times (OR=2.509, p<.001) to have SAD than who were postgraduates. Conclusion: The present data suggest that 45.9% of the participants reached the cut-off for case-ness in LSAS, which is high compared to reports from other populations. As online survey respondents tend to belong to similar demographics, the current results need not be representative of the Omani adult population, which calls for studies that adopt more inclusive survey methods.

Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat®, have failed in Phase III clinical trials. As an alternative strategy, recent efforts have been focussed on the development of more selective inhibitors or targeting other domains than their active sites (e.g., exosites, ectosites) through specific small molecule inhibitors or monoclonal antibodies. Here, we present some examples that aim to better understand the mechanisms of conformational changes/allosteric control of MMPs functions. In addition to MMP inhibitors, we discuss unbiased global approaches such as proteomics and N-terminomics to identify new MMP substrates and achieve a better understanding of the roles of these proteases in diseases.