Background: United Nations Sustainable Development Goals state that by 2030, the Global maternal mortality rate (MMR) should be lower than 70 per 100,000 live births. MMR is still one of Africa's leading causes of death among women. This research aims to study regional trends in maternal mortality in Africa. Methods: We extracted data for Maternal mortality rates per 100,000 births from the World Bank database from 1990-2015. Joinpoint regression was used to study the trends and estimate the annual percent change (APC). Results: Maternal mortality has decreased in Africa over the study period by an average APC of -2.6%. All regions showed significant downward trends, with the sharpest decreases in East Africa. Only the North African region is close to the United Nations' sustainable development goals for Maternal mortality. The remaining sub-Saharan African regions are still far from achieving the goals. Conclusions: maternal mortality has decreased in Africa, especially in East Africa. The only region closed to the United Nations target is North Africa. The remaining sub-Saharan African regions are still far from achieving the goals. These results could be used for the development of Regional Policies.

The paper aims to investigate on the determinants of the capital structure of the Italian SMEs and it is based on a large panel of Italian manufacturing SMEs observed in the years 2001-2013. The analysis achieves a comparative investigation between the capital structure of the firms belonging in the Southern region, the so-called Italian Mezzogiorno that is the slow growing area of the country, and the firms of the Center-northern region of Italy, that is the more developed area of the country. Fixed effect panel techniques applied to the several standard leverage models allows to reaffirm some distinctive features showing differences of the financial behavior of regional firms.

Estimation of the worth of continuity of electricity supply is of interest of industry, authorities and research society. There are numerous methods to calculate the Customer Interruption Costs (CICs). Each method has its advantages and disadvantages. This paper approaches the problem from Distribution System Operators’ (DSOs) point of view and adopts two existing analytical models. One model is used by the Finnish Energy Market Authority and the second one was proposed by the authors at a previous study. The model suggested by the authors as an alternative to the one used by the Finnish Energy Market Authority proposes a simple and straightforward methodology which will provide credible and objective estimations by only utilizing publicly available analytical data. We made use of cost and reliability indices data of 78 DSOs in Finland from the year 2016. In addition to cost estimations, this paper highlights regional differences in CIC estimations in different parts of Finland and critically overviews the existing standard customer compensation scheme in Finland.

Synanthropic flora (weeds, spontaneously developed plants) are plants that accompany humans, appearing as a result of anthropopressure as well as after its cessation. The potential of synanthropic flora in shaping green areas usually brings many measurable benefits that depend on land management in cities. The study aimed to determine the preferences and attitudes of adults towards synanthropic flora in settlement units. The article presents survey results from 447 city residents. The obtained results were statistically analyzed using the k-means clustering method to identify segments of respondents with similar attitudes and preferences toward synanthropic flora. Mann-Whitney U tests were employed to determine statistical differences in the demographic variables among the analyzed clusters of respondents. Additionally, multiple regression analysis was performed to identify the opinions and attitudes towards synanthropic flora, that may influence their greater acceptance in the vicinity of residential areas. The results obtained in multiple regression allow for the statement that the respondent’s evaluation of the level of support for the introduction of more synanthropic vegetation into urban greenery (Yw) grows with the increase of acceptance of synanthropic plants occurrence in surroundings. Respondents’ opinions on the subject of the presence of synanthropic plants were studied using such variables concerning: synanthropic vegetation found in turfgrasses has a positive impact on the visual attractiveness of a site (X1), synanthropic plant communities present themselves better than others (X2), presence of synanthropic vegetation in an estate improves the quality of life in that location (X3), introduction of synanthropic flora into estate arrangements is a positive (X4), support for the use of synanthropic flora for educational purposes - as elements of playgrounds or in the form of environmental workshops (X5). Residents’ acceptance of synanthropic flora in green areas is at a relatively high level.

The orbital elactronic structure of Rare Earth Elements (REEs) contains many unpaired electrons which render them capable of storing large amount of magnetic energy in addition to being critical for hitech applications. Geological deposits are their conventional sources, and the current supply chain relies on production from these deposits. However, given their critical roles in the anticipated global energy transition, there is the need to explore other viable sources to supplement current and future supplies chains. REEs occur in coal as accessory minerals and their concentration in coal ash to levels that rival those of geological deposits has been estab;ished by sophisticated analytical chemical methods. Conmventional hydrometallurgical processes rely on acid leaching, using tioxic mineral acids. Meanwhile, organosulfonic acids have pKa values that rival those of conventional minerals acid and can, therefore, be used in hydrometallurgy but their uses in this regard are not well documented in the literature. In this extensive review, we have covered geological sources of REEs exaustively in addition to showing the potential of organosulfonic acids as environmentally benign lixiviants for REEs extraction from coal ash. We have also shown how process optimization can be achieved using advance technologies while using organisulfonic acids. Moreover, we have shown current and future global market trends regarding the production of select organosulfonic acids, and the anticipated global increase in their production motivates the use of organosulfonic acids as viable lixiviants for REEs extraction from caol ash deposits.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

The central nervous system (CNS) controls movements and regulates joint stiffness with muscle coactivation, but until now few studies have examined muscle pairs during running. This study aims to investigate differences in lower limb muscle coactivation during gait at different speeds from walking to running. Nineteen healthy runners walked and ran at speeds ranging from 0.8 km/h to 9.3 km/h. Twelve lower limb muscles' coactivation was calculated using the time-varying multi-muscle coactivation function (TMCf) with global, flexor-extension, and rostro-caudal approaches. Spatiotemporal and kinematic parameters were also measured. We found that TMCf, spatiotemporal and kinematic parameters were significantly affected by gait speed for all approaches. Significant differences were observed in the main parameters of each coactivation approach, and in the spatiotemporal, and kinematic parameters at the transition between walking and running. Positive and negative strong correlations were found between global coactivation parameters and center of mass displacements, as well as some spatiotemporal parameters, regardless of gait speed. Our findings suggest that walking and running have different coactivation patterns and kinematic characteristics, with the whole-limb stiffness exerted more synchronously and stably in running. The coactivation indexes and kinematic parameters could be the result of global coactivation, which is a sensory-control integration process used by the CNS to deal with more demanding and potentially unstable tasks like running.

(1) Background: Stereological estimations significantly contributed to our anatomical and physiological understanding of the lung by providing an average distribution of measured parameters over the entire lung parenchyma. However, most structural lung diseases show a very inhomogeneous pattern of alterations. (2) Methods: We developed a novel protocol for the analysis of all pulmonary airspaces. Our pipeline starts with high-resolution synchrotron radiation-based X-ray tomographic microscopy (SRXTM) and consists of (i) image segmentation with the combination of the free machine-learning tool Ilastik and ImageJ and (ii) calculation of the airspace diameter distribution of an entire lung using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (ENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas-exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with μCT, suggesting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distributed structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD.

The evolution of the H5 highly pathogenic avian influenza (HPAI) viruses has led to the emergence of distinct groups with genetically similar clusters of hemagglutinin (HA) sequences. In this study, a consensus H5 HA sequence was cloned into the baculovirus expression system. The HA protein was expressed in baculovirus-infected insect cells and utilized as the antigen for the production of an oil emulsion-based H5 avian influenza vaccine (rBacH5Con5Mut). 21-day old SPF chickens were immunized with this vaccine and then challenged at 21 days post-vaccination (dpv) with clade 2.3.2.1, clade 2.3.4.4 and clade 7.2 of H5 HPAI virus, respectively. The chicken sera of vaccinated chickens exhibited high hemagglutination inhibition (HI) titers against the rBacH5 vaccine antigen, while lower HI titers were observed against the different challenge virus H5 hemagglutinins. Furthermore, the rBacH5Con5Mut vaccine provided 100% protection from mortality and clinical signs. Virus isolation results showed that oropharyngeal and cloacal shedding was prevented in 100% of the vaccinated chickens when challenged with clade 2.3.2.1 and clade 2.3.4.4 H5 viruses. When the rBacH5Con5Mut vaccine candidate was administrated at one day of age, 100% protection was demonstrated against challenge of clade 2.3.4.4 virus at 3 weeks of age, indicating the potential of this vaccine for hatchery vaccination. Overall, the rBacH5Con5Mut vaccine candidate with a consensus HA antigen and a single dose can protect chickens against different clades of H5 HPAI viruses throughout the rearing period of broiler chickens without a boost, thus fulfilling the criteria for an efficacious broad-spectrum H5 avian influenza vaccine.

Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Brazil, Russia, China, India, and the Republic of South Africa (BRICS) represent developing economies facing different energy and economic development challenges. The current study aims to forecast energy consumption in BRICS at aggregate and disaggregate levels using the annual time series data set from 1992 to 2019 and to compare results obtained from a set of models. The time-series data are from the British Petroleum (BP-2019) Statistical Review of World Energy. The forecasting methodology bases on a novel Fractional-order Grey Model (FGM) with different order parameters. This study contributes to the literature by comparing the forecasting accuracy and the forecasting ability of the FGM(1,1) with traditional ones, like standard GM(1,1) and ARIMA(1,1,1) models. Also, it illustrates the view of BRICS's nexus of energy consumption at aggregate and disaggregates levels using the latest available data set, which will provide a reliable and broader perspective. The Diebold-Mariano test results confirmed the equal predictive ability of FGM(1,1) for a specific range of order parameters and the ARIMA(1,1,1) model and the usefulness of both approaches for energy consumption efficient forecasting.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

This study investigates the energy profile of a regional hospital in North America using an ASHRAE Level 2 Energy Audit. The audit aimed to assess the efficiency of existing systems, identify areas for improvement, and recommend cost-effective measures to reduce energy consumption and environmental impact. The analysis revealed a well-maintained heating system with efficient boilers. However, a critical concern emerged regarding operational risks due to the lack of redundancy in the cooling system. To address this vulnerability, the study recommends installing an air-cooled chiller for increased operational resilience. The economic feasibility of proposed improvements was evaluated, highlighting the balance between initial investment and long-term savings in energy costs and reduced greenhouse gas emissions. The findings contribute to the discourse on sustainable healthcare practices, emphasizing the importance of energy audits, strategic planning, and redundancy measures for optimized performance and environmental responsibility in hospitals.

South rear-edge populations of widely distributed temperate and boreal tree species such as birches (Betula pubescens and B. pendula) are considered particularly vulnerable to climate warming, and at the same time they constitute genetic reservoirs of drought-adapted ecotypes. Here, we compared radial growth patterns and responses to climate, river or dam flows and a drought index of rear-edge (southernmost) populations (Toledo Mountains, central-southern Spain) with populations located in northern Spain of B. pubescens and B. pendula. Then, we per-formed a comparative analysis across Europe of B. pendula populations. The main climatic con-straint of birch growth was high summer water deficit, although the effect of local hydrological conditions was particularly important in rear-edge populations. We found declining growth trends in rear-edge stands since the early 21st century, related to decreasing water availability and increasing aridity. Our results also suggested distinct growth patterns and climate-growth associations of B. pendula across Europe that show how populations further south and in warmer locations were more sensitive to the drought. In conclusion, drought-induced growth decline can be exacerbated by local human land uses leading to reduced river inflow, thus endangering birch populations at their southern distribution limit. Protection of endangered rear-edge birch populations requires adequate management of local water resources.

High PM10 concentrations are still a significant problem in many parts of the world. In many countries, including Poland, 50μg/m3 is the permissible threshold for a daily averaged PM10 concentration. The number of people affected by this threshold’s exceedance is challenging to estimate and requires high-resolution concentration maps. This paper presents an application of random forests for downscaling regional model air quality results. As policymakers and other end users are eager to receive a detailed resolution PM10 concentration maps, we propose a technique which utilizes the results of regional CTM (GEM-AQ, with 2.5km resolution) and local Gaussian plume model. As a result, we receive a detailed, 250-meter resolution PM10 distribution, which resembles the complex emission pattern in a foothill area in southern Poland. The random forest results are highly consistent with the GEM-AQ and observed concentration. We also discuss different strategies of data training random forest - using additional features and selecting target variables.

An increasing number of aircraft is equipped with wing tip devices, which either are installed by the aircraft manufacturer at the production line or are retrofitted after the delivery of the aircraft to its operator. Installation of wing tip devices has not been a popular choice for regional turboprop aircraft and the novelty of the current study is to investigate the feasibility of retrofitting the British Aerospace (BAe) Jetstream 31 with an appropriate wing tip device (or winglet) to increase its cruise range performance, taking also into account the aerodynamic and structural impact of the implementation. To the best of the knowledge of the authors, no previous study exists which has attempted to assess the winglet retrofit of an existing aircraft type of similar size and operating profile. The optimal winglet design achieved a 2.38% increase of the maximum range by reducing the total drag by 1.19% at a mass penalty of 3.25%, as compared with the baseline aircraft configuration. Other designs were found to be more effective in reducing the total drag, but the structural reinforcement required for their implementation outweighed the achieved performance improvements. Since successful winglet retrofit programs for typical short to medium range narrow body aircraft report even more than 3% of block fuel improvements, undertaking the project of installing an optimal winglet design to the BAe Jetstream 31, should also consider a Direct Operating Cost (DOC) assessment on top of the aerodynamic and structural aspects of the retrofit.

We review the state of dynamical downscaling with scale-constrained regional and global models. The methodology, in particular spectral nudging, has become a routine and well-researched tool for hindcasting climatologies of sub-synoptic atmospheric disturbances in coastal regions. At present, the spectrum of applications is expanding to other phenomena, but also to ocean dynamics and to extended forecasting. Also new diagnostic challenges are appearing such as spatial characteristics of small-scale phenomena such as Low Level Jets.

Currently it was theoritized that cave paintings have meaning more than human and animal interactions. Based on an example from Lascaux cave, a figure of a bull is believed representing Taurus constellation together with the Pleiades. In here this study aims to assess the connections of paleolithic art works in the forms of cave paintings and zoomorphic figures resemble to bovid with possible ancient astronomy and constellation depictions in South East Asia. The study caves were Jeriji Saleh in Kalimantan and Leang Leang and Sumpang Bita caves in Sulawesi where ancient cave paintings and zoomorphic figures date to 40000 years old have been found. The results show that cave paintings in Jeriji Saleh, Leang Leang and Sumpang Bita caves were comparable to the current findings. Those paintings were having bovid like figures with Leang Leang has figure identified as extant Bubalus depressicornis. In Sumpang Bita, this species was depicted in pregnant condition similar to pregnant horse figure in Lascaux cave. Depiction of pregnant figures in cave paintings indicates the use of ancient calendar to determine season based on the animal mating season. Bovid figure in Jeriji Saleh was illustrated in the same posture like auroch bovid in Lascaux cave and this indicates that cave paintings in Jeriji Saleh have been used to visualize Taurus constellation. The postures of bovid paintings in Leang Leang were different and it is interpreted to visualize Capricorn constellation. Another significant similarity between Lascaux and Leang Leang caves can be seen in paintings depicting a shaft scene with the presences of 3 similar figures include dying man, speared bovid and small zoomorphic figures. This concludes that the caves with their wall painting were not merely functioned as media for ancient art works, whereas it has functioned as paleolithic planetarium and this knowledge was globally widespread.

Patients with predominantly antibody deficiencies (PAD) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate their possible contribution to PAD clinical phenotype. Eight CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474) which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD, in order to identify patients with a higher risk for liver disease.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

During HIV-1 virus assembly the genomic RNA (vRNA) is selected for packaging by the viral protein Gag because it contains a specific packaging signal, Psi. While there have been numerous studies of Gag-Psi interactions, there is almost no information on kinetic aspects of this interaction. We have investigated the kinetics of Gag binding to different RNAs using switchSENSE DRX2 technology. We measured the association rate of Gag binding to monomeric Psi, to a “Multiple Binding Site Mutant” Psi that is inactive for genome packaging in vivo, and to a scrambled Psi. We discovered that Gag binds more rapidly to Psi RNA than to the mutant or scrambled RNAs. Furthermore, rapid Gag association kinetics are retained within sub-regions of Psi: Gag associates more rapidly with RNA containing only the 3’ two of the three Psi stem-loops than with monomeric RNA containing the 5’ two stem-loops or a scrambled RNA. No differences were detectable with individual Psi stem-loops. Interestingly, the rate of binding of Gag molecules to Psi increases with increasing Gag concentration, suggesting cooperativity in binding. The results are consistent with the hypothesis that selectivity in packaging derives from kinetic differences in initiation of particle assembly.

Chronic Myeloid Leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a Tyrosine Kinase Inhibitor (TKI), can be effectively used as therapy for CML. However, imatinib can affect bone turnover, thus having clinical implications on the bones of CML patients undergoing long-term imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving imatinib still need further study. A combination of imaging techniques such as Bone Mineral Density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and Osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving imatinib. This article explains the rationale for using BMD, CTX-1, and Osteocalcin as monitoring parameters of bone remodeling in CML patients receiving imatinib. First, the physiological process of bone turnover will be explained. Then, we describe the role of tyrosine kinase in bone metabolism. Next, the impact of imatinib on BMD, CTX-1, and Osteocalcin will be explained. In conclusion, the assessment of bone health of CML patients on Imatinib should include both BMD tests and bone turnover marker assays such as CTX-1 and Osteocalcin.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

Historic expeditions are events that are flavored by exploratory, scientific, military or geographic characteristics. Such events are often documented in literature, journey notes or personal diaries. A typical historic expedition involves multiple site visits and their descriptions contain spatiotemporal and attributive contexts. Expeditions involve movements in space that can be represented by triplet features (location, time and description). However, such features are implicit and innate parts of textual documents. Extracting the geospatial information from these documents requires understanding the contextualized entities in the text. To this end, we developed a semi-automated framework that has multiple Information Retrieval and Natural Language Processing components to extract the spatiotemporal information from a two-volumes historic expedition gazetteer. Our framework has three basic components, namely, the Text Preprocessor, the Gazetteer Processing Machine and the JAPE (Java Annotation Pattern Engine) Transducer. We used the Brazilian Ornithological Gazetteer as an experimental dataset and extracted the spatial and temporal entities from entries that refer to three expeditioners’ site visits and mapped the trajectory of each expedition using the extracted information. Finally, one of the mapped trajectories was manually compared with a historical reference map of that expedition to assess the reliability of our framework. The reference map was manually prepared in previous research work by others.

Biodiversity monitoring is a seminal key for understanding the delivery of ecosystem functions and services. Mediterranean forests and woodlands harbor the vast majority of regional vascular plant diversity, and hence, they are a good surrogate for detecting changes in biodiversity linked to global change. In this work, we present a database resulting from the study of vascular plant diversity in multi-scale plots of 0.1 ha, measured around the first decade of this century and located in Mediterranean forest environments. Diversity profiles are calculated from Hill numbers (0, 1 and 2) for local (α) and regional (ϒ) diversity, as well as multiplicative calculation of differential diversity (β). Main Mediterranean forests sampled had a medium coverage of 51 % and stand dominant height of 10.6 m being monospecific in two thirds of the cases. Local diversity reaches its highest values ​​(around 78 species per 0.1 ha) in Holm oak dehesas, with values ​​below 50 species for the set of the most productive forest stands dominated by species of the genus Pinus. As regards the contribution to regional diversity, it is the broadleaf formations that contribute the most, with stone pine forests and dehesas in an intermediate position, and pine forests contributing the lowest in species richness terms.

Ammonium sulfate has been utilized in agriculture; however, there is a dearth of research on its application in maize cultivation subsequent to the implementation of nitrification inhibitors or coating. This study aims to analyze the impacts of various combinations of ammonium sulfate fertilizers on soil nutrients, plant nutrient uptake, yield, and fertilizer utilization efficiency in maize cultivation to ascertain the optimal and stabilized disposal method for ammonium sulfate. A completely randomized design was employed with five treatments (AU, the control using urea; AS, treatment using ammonium sulfate; ASN, treatment using ammonium sulfate with a nitrification inhibitor; ASG, treatment using oil-coated ammonium sulfate; ASD, treatment using oil-humic acid-coated ammonium sulfate). Results showed that: (1) Compared with AU and AS, ASN, ASG and ASD decreased the leaching rates of TN, NH4+-N and NO3-N to the 10-20 cm soil layer, and more residual N was obtained in 0-10 cm soil layer. The first-order kinetic equation Nt=N0(1-e-kt) can better fit the process of nitrogen accumulation and release, and the N release rate constant is AU>CK>AS>ASH>ASN>ASD; (2) Compared with AU and AS treatments, the plant dry weight, grain dry weight, spike width, spike length, and yields of maize increased by 8.85-11.08%, 12.98-14.15%, 2.95-3.52%, 5.50-5.65%, and 43.21-51.10% under ASG treatment respectively. The impact of effective spike number on maize yield was found to be significant, as demonstrated by the path analysis conducted in this study. Furthermore, the accumulation levels of nitrogen, phosphorus, and potassium within above-ground plants significantly increased under the ASG treatment compared to the AU and AS treatments. The partial productivity of nitrogen, phosphorus, and potassium increased by 1.43-1.51-fold under ASG treatment, while grain nitrogen balance, grain phosphorus balance, and grain potassium balance increased by 1.41-1.58-fold, 1.51-1.95-fold, and 1.15-l.96-fold respectively. The oil-coated ammonium sulfate, therefore, exhibited the optimal slow-release effect of nutrients, thereby achieving superior performance in enhancing maize production and efficiency.

The effective utilization of medium-high temperature geothermal energy is pivotal in reducing carbon emissions and plays a crucial role in developing clean energy technologies. The MiDu ge-othermal field, situated in the southeastern region of Dali Prefecture, Yunnan Province, lies within the Mediterranean-Himalayan high-temperature geothermal belt and is characterized by abundant geothermal resources. However, due to its considerable depth, exploration poses significant risks, resulting in a total utilization rate of less than 0.5% of the total reserves. This study employs natural seismic data to perform a tomographic analysis of the geothermal system in the Midu basin. By examining the P-wave velocity (Vp) and velocity ratio of P-wave and S-wave (Vp/Vs) at various depths, the findings reveal that the basin comprises two distinct structural layers: the thrust basement of the Mesozoic and Paleozoic eras and the strike-slip extensional sedimentary layer of the Cenozoic era. A low-velocity anomaly in the central basin corresponds to the loose Cenozoic sedimentary layer. In contrast, high-velocity anomalies at the basin edges correlate with boundary faults and the Mesozoic-Paleozoic strata. Below a depth of 4 km, the Red River Fault and MiDu Fault continue to dominate the basin's structure, whereas the influence of the Malipo Fault dimin-ishes. The MiDu Fault exhibits higher thermal conductivity than the Yinjie Fault. It interfaces with multiple carbonate and basalt formations characterized by well-developed pores and fractures, making it a crucial conduit for water and a control point for geothermal storage. Consequently, the existence of high temperature geothermal resources for power generation should be concentrated around the Midu fault on the western side of the basin, while the Yinjie fault area is more favorable for advancements in heating and wellness.

Unmanned aerial vehicles (UAVs), commonly known as drones, present a cost-effective solution for the swift collection of data from vast and remote areas that are otherwise difficult to access. The Mediterranean Basin, known for being a hot spot for plant biodiversity, hosts several habitats and taxa of significant naturalistic value. However, many of these areas are often inaccessible to botanists, making exploration and research challenging. The aim of this paper is to involve the utilization of drone surveys and open-source software for botanical research. Our primary goal is to show the effectiveness of these tools in the field and demonstrate their practical application in Natura 2000 sites. The protected area chosen for this research is Rocca di Novara, situated in northeastern Sicily. Thanks to our drone investigations, we were able to capture images of the mountain’s side that is inaccessible to humans. This allowed us to observe the habitat of some species in detail. One of the most fascinating discoveries was the reappearance of Saxifraga callosa subsp. australis, which had not been confirmed in this area for over 140 years. Using drones for botanical research can boost field research, making monitoring easier and more cost-effective over time, especially in Natura 2000 sites.

The BRAFV600E mutation, found in approximately 50% of melanoma cases, is associated with aggressive tumor behavior and poor prognosis. This study aimed to assess its impact on immunogenic cell death (ICD), a pivotal cytotoxic process triggering anti-tumor immune responses. Through comprehensive in silico analysis of The Cancer Genome Atlas data, we explored the association between the BRAFV600E mutation, immune subtype dynamics, and tumor mutation burden (TMB). Our findings revealed that the mutation correlated with a lower TMB, indicating a reduced generation of immunogenic neoantigens. Investigation into immune subtypes reveals an exacerbation of immunosuppression mechanisms in BRAFV600E-mutated tumors. To assess the response to ICD inducers, including doxorubicin and Me-ALA-based photodynamic therapy (PDT), compared to the non-ICD inducer cisplatin, we used distinct melanoma cell lines with wild-type BRAF (SK-MEL-2) and BRAFV600E mutation (SK-MEL-28, A375). We demonstrated a differential response to PDT between the WT and BRAFV600E cell lines. Further transcriptomic analysis revealed upregulation of IFNAR1, IFNAR2, and CXCL10 genes associated with the BRAFV600E mutation, suggesting their involvement in ICD. Using a gene reporter assay, we showed that PDT robustly activated the IFN-1 pathway through cGAS-STING signaling. Collectively, our results underscore the complex interplay between the BRAFV600E mutation and immune responses, emphasizing a putative correlation between tumors carrying the mutation and their responsiveness to therapies inducing the IFN-1 pathway, such as the ICD inducer PDT, possibly mediated by the elevated expression of IFNAR1/2 receptors.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "Classic" BPD, as per the original description, is less common now. "New BPD," which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving due to medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36) and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 have been observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening the infection control measures.

(1) Background: This study evaluated the spatial position and anatomical characteristics related to impacted third molars by map-reading strategy using cone beam computed tomography (CBCT). (2) Methods: To determine the positioning of impacted third molars on CBCT it was used Winter's and Pell &amp; Gregory's classifications, and the presence of external root resorption in mandibular second molars were based on Herman´s classification. The relationship between the mandibular third molar root apex and the mandibular canal was also analyzed. Fisher’s exact test was used to comparative statistical analysis. The significance level considered was 5%. (3) Results: The results showed that according to Winter's classification, 48.06 % of impacted teeth were in the mesioangular position. Using Pell &amp; Gregory's classification, 43.22% of the impacted molars were in the position B and C, and 54.2% of the teeth were class II. 69.7% of teeth showed an absence of contact between the root apex and the mandibular canal and there was no occurrence of external root resorption in the distal of second molar in 88.7%. (4) Conclusions: The map-reading strategy using CBCT scans for anatomical positions and characteristics of impacted third molars increases professional confidence and establishes a parameter of quality and safety in the surgical procedure for the patient.

TThe following three objectives were tested in this study: (1) investigate the utility of low-altitude remote sensing using UAS technology to compare the effects of different N application systems in rice production; (2) use spatial extrapolation to scale up plot-level generated to farmer field rice yield data based on crop spectral signatures, and (3) predict and map out rice productivity as a function of N placement systems. Images were captured on a UAV platform at midseason of the rice crop. Orthomosaics were developed for selected fields in rice-producing zones. Grain yields were assessed from low, medium, and high crop health plots delineated based on NDVI values. On the plot scale, UDP outyielded non-UDP by 0.84%. Individual plot yield data were scaled up to the farmer field level through Jenks natural breaks classification and es-tablishing an empirical relationship between OSAVI and plot yields. Assessment of the scaled-up field levelfield-level data also confirmed the superiority of UDP N man-agement over the non-UDP systems in promoting rice yields. Scaling up plot scale da-ta to whole field levels also facilitated generating and mapping expected yield maps for individual farmer fields in the three zones studied. This study has established a tangible simple but tangible protocol protocol for predicting and mapping rice yields in small-scale farmer fields using UAS data.

The rural road landscape is crucial in forming rural areas' landscape character (LC). As a platform for portraying the rural landscape, the rural roads demonstrate the area's unique natural and cultural characteristics to the visitors. However, with the continuous development of rural areas, the rural LC has been severely impacted, thus impacting visitors' visual experience. In order to preserve and protect the rural landscape, this study aims to assess the visual quality of rural road landscapes based on public preference and heatmap analysis. The results indicated that most of the participants had a higher level of preference for rural landscapes with open horizontal views represented by agricultural areas such as paddy fields. It was also found that different paddy field characters based on their planting stages can also positively affect the visual quality of rural road landscapes. The study also revealed that rural LCs with roadside settlements, commercial structures, mixed agricultural crops, and vegetation received low preference ratings. These characters negatively impact the visual quality of the rural road landscape. These findings provide significant insight for planners and decision-makers regarding protecting and preserving the essential rural road landscapes for the rural tourism experience.

An increasing number of studies have shown that safety culture factors have a substantial influence on safety performance in a variety of industrial sectors. These factors' impact on safety performance is unclear, especially at the public service and statutory authorities. On the other hand, the understanding of indicators for safety performance in every working sector in Malaysia is on the continuing progress. Hence, this study's contribution is to explore the influence of safety culture factors (i.e., management commitment and supervision in safety, safety system) and safety competence on safety performance in government paramedic training institutes. IPMA (importance-performance map analysis) is a technique used in Smart PLS to determine the significance and performance of each of these factors. The study was conducted via an online survey and involved 258 safety and health committee members in Ministry of Health paramedic training institute. As a matter of relevance, the IPMA's empirical data study revealed that management commitment and supervision in safety were the predominant factors in determining safety performance. Meanwhile, for performance, the findings showed that worker involvement, safety system, and safety competence perform well in determining the safety performance.

The current study investigated the use of two-dimensional spatial distribution mapping representing the chlorophyll-a level in a river generated via an unmanned aerial vehicle (UAV) and an unmanned surface vehicle (USV). A domestically developed UAV (Remo-M, Uconsystem Inc., Korea) and a USV developed by our research team were used to collect data from the Nae Seong stream in Korea. An adaptation of the “Data Cleaner” tool was developed and used for USV data processing and analysis. The operation of the autonomous USV was successful. Four previously described indices for quantifying algal blooms in rivers were utilized to create chlorophyll-a images, the normalized difference vegetation index (NDVI), the normalized green red difference index, the green normalized difference vegetation index (GNDVI), and the normalized difference red edge index. The suitability of the linear regression analysis of the correlation between the spectral indices obtained using the UAV and the in situ chlorophyll-a data obtained using the USV was evaluated with the coefficient of determination (R2) at a significance level of p &lt; 0.001. In field application and correlational analysis the NDVI was strongly correlated with chlorophyll-a (R2 = 0.88, p < 0.001), and the GNDVI was moderately correlated with chlorophyll-a (R2 = 0.74, p < 0.001). The map of chlorophyll-a was successfully quantified using the UAV and USV hybrid platforms.

I examine national environmental security policy cultures to assess the opportunities for increasing global environmental security. The question is whether the difficulties in modeling the state's ecological security are a consequence of limitations in the coherence of the four dogmas: ecological security, sustainable development, social responsibility and environmental management. The presented fragments of theoretical research explain the question by presenting the logic of the constructive value of the national culture of ecological safety policy. I conducted empirical research based on 18 development strategies of regional cities in Poland. The multi-criteria method made it possible to identify and describe a micro-community reflecting the macroscopic observation of regional cities as an emerging whole of the state’s development. Assumption: ownership of the environmental aspects of cities is a natural quantity influencing the ecological security of the state in the contemporary global civilization system. I have formulated new definitions: ecological security of the state, culture of ecological security policy, sustainable development and socially responsible and sustainable development of the city. I have developed 13 catalogues of elements of the structure of the development strategy of regional cities in Poland, containing 1 390 public services. I have shown when there is a lack of culture of the state's ecological security policy in the global ecological security system according to the cause-effect principle. I have been conducting research since 2019.

The research paper comprehensively and consistently addresses all relevant theoretical areas related to the topic and includes an extensive empirical analysis of the absorption of EU funds and their impact on the sustainable development of Croatia, Slovenia, Hungary, and Poland. The analysis aims to investigate the efficiency of the absorption of funds from the EU, the impact of these funds on regional development of countries, as well as the reasons for such impacts. The "Regional Development Model Based on EU Funds" was tested with the aim of applying the model to the Republic of Croatia, countries in the region, and other European countries to achieve a higher level of absorption of financial resources from the available EU funds. Data for the empirical analysis were collected using a highly structured survey questionnaire on a sample of 244 respondents involved in the preparation and implementation of EU-funded projects. The contribution of economic science in theoretical terms arises from the development of scientific knowledge and ideas about the importance of increasing the number of development projects that will increase the absorption of funds from the European Union, thereby increasing economic activities in Croatia and the region. The expected contribution of economic science in the applied sense is based on the formulation of the "Regional Development Model Based on EU Funds," which is based on the application of knowledge, good practices, and stakeholder experiences, considering relevant indicators from available sources. The greatest contribution is demonstrated through testing the "Regional Development Model Based on EU Funds," which is applicable to the Republic of Croatia, countries in the region, and other European countries over a longer period. Finally, research of the impact of EU funds on the regional development of recipient countries is considerably less represented and very modest, only in the "upswing" of systematic scientific research. The research aims to fill the gaps in research and encourage thinking of key stakeholders responsible for regional development, who should eventually realize the importance of defining a regional policy aimed at EU funds as a key to regional development and reducing regional disparities within countries.

The paper is devoted to the investigation of regional observability with constraints on the state of semilinear parabolic systems. The purpose is to reconstruct the initial state between two prescribed functions only on an internal subregion $\omega$ of the system evolution domain $\Omega$. The proofs use two approaches, the subdifferential and HUM approach. Finally, a numerical example is provided to verify the effectiveness of our theory results.

The Surface Water and Ocean Topography (SWOT) mission, to be launched in 2021, will provide water surface elevations, slopes, and river width measurements for rivers wider than 100 m. In this study, synthetic SWOT data are assimilated in a regional hydrometeorological model in order to improve the dynamics of continental waters over the Garonne catchment, one of the major French catchments. The aim of this paper is to demonstrate that the sequential assimilation of SWOT-like river depths allows the correction of river bed roughness coefficients and thus simulated river depths. An extended Kalman Filter is implemented and the data assimilation strategy was applied to four experiments of gradually increasing complexity regarding observation and model error over the 1995-2000 period. With respect to a “true” river state, assimilating river depths allows the proper retrieval of constant and spatially distributed roughness coefficients with a root mean square error of 1 m1/3 s-1, and the estimation of associated river depths. It was also shown that river depth differences can be assimilated, resulting in a higher root mean square error for roughness coefficients with respect to the true river state. The last study shows how one can take into account more realistic sources of SWOT error measurements, in particular the importance of the estimation of the tropospheric water content in the process.

The bioindicator potential of seagrass ecosystems in coastal trace metal monitoring is low for tropical island ecosystems. This study evaluated the bioindicator potential of six seagrass species exposed to anthropogenic trace metal pollution in the Andaman and Nicobar Islands (ANI) of India. Sediment and seagrass biomass, samples were analyzed for trace metals (Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Zn) from four locations of ANI exposed to anthropogenic contamination. Geo accumulation Index values indicated moderate trace metal contamination in seagrass sediment. Seagrass trace metal accumulation from sediment was both species-specific and location- specific for ANI. Small seagrass species such as H. ovalis, H. beccarii and H. uninervis accumulated the maximum concentration of six trace metals (Cr, Cu, Fe, Ni, Pb, Zn) in their tissues compared to big seagrass species like T. hemprichii and E. acoroides of ANI. This study indicates leaves of small seagrass and roots of big seagrass species can serve as short- and long-term bioindicators respectively, of coastal trace metal contamination in tropical islands of ANI.

This study explores the potential of Eisenia fetida (Savigny) in vermicompost production within vermipits during winter months in the Rampur region of Uttar Pradesh, India. The vermipits were inoculated with 0.33 kg of E. fetida per pit, against the recommended rate of inoculation for assessment of real-time potential of earthworm on seasonal and regional grounds. The results revealed a significant increase in earthworm population, with three times production (4.1 kg) of the inoculated number (1.0 kg). The productivity dynamics of compost vs E. feida revealed a notable threefold and fourfold effectiveness, respectively. This dual advantage signifies the success of composting process, with the increased worm population indicating enhanced decomposition. The study attributes the combination of regional and edaphic factors viz., sandy loam soil with high humus content and good water passage, facilitating earthworm survival, reproduction and decomposition of agricultural waste. The loose and perforated soil structure allowed easy penetration of earthworms, transforming the soil into fertile compost. The research emphasizes the importance of soil moisture of semi-arid ecosystems thus highlighting the seasonal significance governing earthworm activity. The study provides insights into the mechanical ability of earthworms, its sensitivity to soil compaction and the influence of high hydration of the region. Inoculation during the winter period indicates increased earthworm activity setting the stage for enhanced compost production in the upcoming hot periods of summer months. The findings suggest that optimizing vermicomposting practices with altered feeding stocks, could further improvise compost and earthworm production and productivity in subsequent seasons. The study contributes for sustainable utilization of E. fetida in composting, its regional and seasonal efficacy turns trash to treasure for enhanced agricultural efficacy.

Cultural routes are a composite set of heritage, referring to any ancient routes of human communication. As one of the key products of cultural tourism, they providing visitors with a rich cultural experience across regions. We systematically review reports and studies related to the tourism development of 38 cultural routes cases around the world, with a special focus on their distribution, typology, planning patterns and tools for cultural tourism. We summarized eight tools, there are some differences in how often these eight tools are used by the different types of routes and different planning patterns for routes tourism. The study also made an evaluation system based on the conservation principles of cultural routes to find out how different tools of tourism affect the conservation and development of the historical region. It was found that although many efforts have been made by tourism decision-makers to protect and develop cultural routes there are still many problems and challenges in the process of tourism development along cultural routes. We close the paper by making a few recommendations for decision makers and researchers concerning future routes’ tourism planning and study.

Youth is the essential entrepreneurial force for every country's social, political, and economic development. Urban youth make up about 34.27 percent of the population in Ethiopia. The youth unemployment crisis is one of the serious challenges that Ethiopia is facing nowadays, and it should be mentioned in the nation's public discourse. Therefore, the main objective of this study is to specify the socioeconomic and demographic factors that influence urban youth unemployment in the Somali Regional State, specifically in Jigjiga, Degahbour, Kebridahar, Gode, and Dollo Ado towns. Both primary and secondary data sources were employed. A multi-stage sampling technique has been used to select 385 sample respondents from the total population of the study. This study found that almost 63% of youth in the study area were unemployed, and a large number of unemployed youths live in Jigjiga and Dollo Ado Towns as compared to other city administrations. The econometric model's findings indicate that factors like gender, education level, work experience, access to credit, access to information, time applied for job vacancy, active job seeker, social network (network with clan elders, government officials, businessmen, and other friends), and residence in Jigjiga and Gode town have a significant association with the likelihood of youth unemployment in the Somali regional state. Therefore, this study recommends that the regional government and local city administration should develop effective policies and strategies to address the underlying causes of gender inequality, improving access and quality of education, supporting freshman graduates to find jobs, providing access to credit and job vacancies, ensuring fair and free job competition, and managing youth migration for job seeking.

The COVID-19 pandemic made it harder to communicate accurate information about vaccines because of the spread of misinformation. The European Medicines Agency (EMA) tried to reas-sure the public by communicating about the development and approval of COVID-19 vaccines. They surveyed patients/consumers, healthcare professional organizations, and individual stake-holders to see if their core information materials were informative and well understood. They also asked about the public's preferred communication channels. The surveys showed that indi-vidual patients/consumers generally prefer to get information about COVID-19 vaccines from the internet or mass media. Organizations and individual healthcare professionals prefer to get in-formation from national and international health authorities' sources. This supports EMA's ap-proach of using media, stakeholder engagement, and web-based formats to communicate about COVID-19 vaccines. Both at the EU and local levels, participants had a good understanding of the key messages from regulators and found the materials useful and relevant. However, some im-provements were recommended to the visuals, texts, and dissemination formats. These recom-mendations were generally consistent in both contexts. User-testing of proactive communication materials aimed at prebunking misinformation during a public health crisis helps to ensure that users understand the development and safety safeguards of novel vaccine technologies. This in-formation can then be used as a basis for evidence-based communication activities by regulators and public health bodies in an emergency context.

Background: Intradialytic hypotension (IDH) is a critical pathological condition associated with all−cause mortality in patients undergoing hemodialysis (HD). However, few studies have investigated IDH-related changes in hepatic and cerebral regional tissue oxygen saturation (rSO2). This study investigated IDH-induced changes in hepatic and cerebral rSO2. Methods: Hepatic and cerebral rSO2 during HD were measured using an INVOS 5100C oxygen saturation monitor, and their percentage (%) changes during IDH development were analyzed. Ninety-one patients undergoing HD were investigated, including 20 with IDH development. Results: In patients with IDH, % changes in hepatic and cerebral rSO2 decreased at IDH onset. Additionally, the % change in hepatic rSO2 was significantly larger than those in cerebral rSO2 (P < 0.001). In patients without IDH, no significant differences were found between the % changes in hepatic and cerebral rSO2 at time of the lowest systolic blood pressure during HD. Multivariable linear regression analysis showed that the difference between the % change in cerebral and hepatic rSO2 was significantly associated with IDH development (P < 0.001) and ultrafiltration rate (P = 0.010). Conclusion: Hepatic and cerebral rSO2 significantly decreased in IDH development and hepatic rSO2 was more largely decreased than cerebral rSO2 at IDH onset.

This paper provides an optimization strategy for flexible operation at the system level, so as to guide the real-time flexible ramping of the power grid. Firstly, the concept of regional power grid flexibility was clarified, and the ramping factor is proposed as a flexibility metric. On this basis, taking the output priority of each node as the objective function and considering constraints such as line flow, power balance, and system flexibility, a mathematical model for regional power grid transmitting flexible power externally is proposed. Compare with the traditional models, this model focuses more on flexibility rather than economy. The case analysis based on the improved IEEE 30-Bus System verifies the feasibility and effectiveness of the proposed strategy and its advantages over the traditional models.

The administration of regional neuraxial analgesia for pain relief during labor is widely recognized as a safe and effective method involving medication delivery into the epidural or subarachnoid space in the lower back. This study proposes an innovative semantic image segmentation methodology emphasizing enhanced interpretability using convolutional Random Fourier Features and layer-wise weighted class-activation maps tailored explicitly for foot segmentation in regional analgesia monitoring. Namely, our contribution is twofold: i) a novel Random Fourier Features layer is introduced to deal with image data to enhance three well-known architectures (FCN, UNet, and ResUNet); ii) three novel quantitive measures are presented to evaluate the interpretability of a given deep learning model devoted to segmentation tasks. Our approach is rigorously evaluated on a demanding dataset of foot thermal images from pregnant women who received epidural anesthesia. Its small size and considerable variability characterize the dataset. Our validation results demonstrate that the proposed methodology not only achieves competitive foot segmentation performance but also significantly enhances the explainability of the process, rendering it well-suited for applications such as epidural insertion during labor.

This study used a two-stage network data envelopment analysis model to measure the water use efficiency of 108 cities in the Yangtze River Economic Belt in the initial water use and wastewater treatment phases from 2009 to 2019. We used the Dagum Gini coefficient to decompose the urban water use efficiency of six major urban clusters in the Yangtze River Economic Belt. We also used σ convergence and β convergence types to test the convergence characteristics of urban water use efficiency of six major urban clusters in the Yangtze River Economic Belt. This study found that the overall low level of water use efficiency in cities in the Yangtze River Economic Zone mainly stems from the low level of water use efficiency in the wastewater treatment stage. The 108 cities in the Yangtze River Economic Zone are divided into four types based on the average values of water use efficiency in the initial use and wastewater treatment phases; the highest number of cities are in the double-low category, with low average values of water use efficiency in the initial use and wastewater treatment phases. During the study period, spatial differences in urban water use efficiency in the Yangtze River Economic Zone narrowed, with the differences stemming mainly from hyperdensity, followed by intra- and inter-regional differences. Meanwhile, there is convergence in urban water use efficiency in the Yangtze River Economic Belt; significant β convergence in the urban agglomerations of the Yangtze River Delta, Jianghuai, middle reaches of the Yangtze River, Chengdu–Chongqing, and Central Yunnan; and insignificant β convergence in the Central Qian urban agglomeration. After considering control factors, such as industrial structure, financial development level, environmental regulation, economic development level, and science and education development level, the water use efficiency of the six major urban clusters in the Yangtze River Economic Belt converges faster, but the influence of these control factors on the water use efficiency of each urban cluster is heterogeneous. Research results have reference value for the development of improvement strategies on differentiated urban water use efficiency in the Yangtze River Economic Belt.

The interaction between different regions normally is reflected by the form of the stream. For example, the interaction of the flow of people and flow of information between different regions can reflect the structure of cities’ network, and also can reflect how the cities function and connect to each other. Since big data has become increasingly popular, it is much easier to acquire flow data for various types of individuals. Currently, it is a hot research topic to apply the regional interaction model, which is based on the summary level of individual flow data mining. So far, previous research on spatial interaction methods focused on point-to-point and area-to-area interaction patterns. However, there are a few scholars who study the hotspot interaction pattern between two regional groups with some predefined neighborhood relationship by starting with two regions. In this paper, a method for identifying a similar hotspot interaction pattern between two regional groups has been proposed, and the Geo-Information-Tupu methods are applied to visualize the interaction patterns. For an example of an empirical analysis, we discuss China’s air traffic flow data, so this method can be used to find and analyze any hotspot interaction patterns between regional groups with adjoining relationships across China. Our research results indicate that this method is efficient in identifying hotspot interaction flow patterns between regional groups. Moreover, it can be applied to any analysis of flow space that is used to excavate regional group hotspot interaction patterns.

This paper proposes a new non-radial biennial Luenberger energy and environmental performance index (EEPI) to measure the EEP change in various Chinese cities. The sources of EEP change, in terms of technical efficiency change and technological change, are examined by Luenberger EEPI. The contributions from specific undesirable outputs and energy inputs to the EEP change are identified by means of the non-radial efficiency measure. The proposed approach is applied to evaluate the EEP of the industrial sector in 283 cities in China over 2010-2014. Factors influencing the emission abatement potential are investigated by employing geographically weighted regression (GWR) model. We find that 1) changes in EEP can be attributed to technological progress but that technological progress slows down across the study period; 2) the soot emission performance experiences a downtrend among four specific sub-performances in line with the truth that severe haze happened frequently in China; 3) the best performers begin to move from the coastal to inland cities with the less resource consumption and higher ecological equality; 4) cities with the strongest positive effect in regards to pollution intensity on emission abatement potential are located in the areas around the Bohai Gulf, where air pollution is particularly severe.

Widespread poverty is the most serious threat and social problem that Bangladesh faces. Regional vulnerability to climate change threatens to escalate the magnitude of this poverty. It is essential that projections of poverty be made while bearing in mind the effects of climate change. The main purpose of this paper is to investigate the agrarian sub-national regional analysis of climate change vulnerability in Bangladesh under various climate change scenarios and its potential impact on poverty. This study is relevant to socio-economic research on climate change vulnerability and agriculture risk management and has the potential to contribute new insights to the complex interactions in household income and climate change risks to agricultural communities in Bangladesh and South Asia. The current study uses analysis of variance, cluster analysis, decomposition of variance and log-normal distribution to estimate the parameters of income variability that ascertain vulnerability levels and help us to understand the poverty levels that climate change could potentially incur. It is found that the income share in income sources revealed that income category shares across the various regions of Bangladesh are far from uniform. The variance decomposition of income showed that agricultural income in Mymensingh and Rangpur is the main cause of income difference. Moreover, large variance of agricultural income in the regions is induced by gross income from rice production. Additionally, constant reduction of rice yield due to climate change in Bangladesh is not such a severe problem for farmers, however, the extreme events like flood, flash flood, drought, sea level rise, and greenhouse gas emission based on RCPs could increase the poverty rates in Mymensingh, Rajshahi, Barisal, and Khulna regions that would be highly affected by unexpected yield loss due to extreme climatic events. Therefore, research and development of adaptation measures to climate change for regions where farmers are largely dependent on agricultural income is important.

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

The research presented in the article is devoted to the study of the influence of phase compounds on the friability of the Fe-Si-Mn-Al complex alloy. The urgency of the problem lies in the development of technology for producing a non-scatterable alloy from manganese-containing ores and high-ash coals. The main goal of the work is to determine the range of alloy compositions and the resulting phases that affect the dispersibility of the alloy, which is critically important for its industrial implementation. Research methods include thermodynamic diagram analysis (TDA) using data on the standard enthalpy of formation of intermetallic compounds, as well as experimental tests in an ore-thermal electric furnace with a capacity of 200 kV*A. The results show that Fe-Si-Mn-Al complex alloys form a variety of silicide and aluminide phases, including intermetallic compounds and ternary systems, which is critical for understanding and controlling their physicochemical properties. When smelting a complex alloy, the content of leboite (Fe3Si7) in the Fe-Si-Mn-Al system plays a significant role. The development of smelting technology will be aimed at avoiding the FeSi2-Fe3Si7-F2(FeAl3Si2)-Mn11Si19 tetrahedron area. This approach to controlling the composition of a complex alloy is critical to ensuring its consistent friability properties in industrial applications. Thus, this work represents an important step in understanding the physical properties and stability of Fe-Si-Mn-Al complex alloys, which have potential for widespread use in metallurgical and other industrial applications.

Ceratonia siliqua L. is a medicinal plant that has long been used in traditional Moroccan medicine to treat many diseases. This study aimed to assess the impact of the stages of the immature phase of carob pulp (M1, M2, M3, M4, and M5) on phytochemical composition, antioxidant activity, and antidiabetic activity of Ceratonia siliqua L. The identification of the phenolic profile by HPLC-UV/MS-MS and the study of the antidiabetic effect by in silico, in vitro, and in vivo studies were carried out for extracts with a high content of phenolic compounds from immature wild carob pulp from the communes of Timoulit (TM), Bin Elouidane (AW), and Ouaouizerth (TG) in the province of Azilal in the Beni Mellal-Khenifra region. The results revealed a gradual increase in total sugar content over the pulp's ripening period, reaching a value of 2134 ±56.23 mg GE/100 g fresh matter (FM) for TG. The three locations showed peak values for total polyphenol content (TPC), total flavonoid content (TFC), and total condensed tannin (TCT) at the M2 stage. AW has the highest concentrations of TPC (3819 ± 226.4 mg GAE/100 g FM), TFC (1034 ± 57.08 mg QE/100 g FM), and TCT (1472 ± 28.46 mg CE/100 g FM). The DPPH assay (7892 ± 296.1 mg TE/100 g FM) and the FRAP assay (278.2 ± 7.85 mg TE/100 g FM) both demonstrate that the TG zone is a highly potent antioxidant zone. In contrast, the AW site exhibits a markedly elevated value of 725.4 ± 103.6 mg TE/100 g FM in the ABTS assay. HPLC-UV-MS/MS analysis showed that the methanolic extracts of immature carob pulp (MEICP) from the three areas contained several different chemical compounds. The most prevalent were 3-O-p-coumaroyl-5-O-caffeoylquinic acid, quercetin 3-methyl ether, gallic acid, and galloylquinic acid. Immature carob pulp extract. (ICPE) from AW showed the strongest in vitro inhibition of pancreatic α-amylase (IC50 = 0.405 µg/mL) and TG extracts were most potent against intestinal α-glucosidase (IC50 = 0.063 µg/mL). In vivo, AW, TG, and TM extracts significantly reduced postprandial glycemia in rats, with AW having the greatest effect. These results highlight the antidiabetic potential of ICPE. The 3-O-p-Coumaroyl-5-O-caffeoylquinic acid showed a better affinity for α-amylase compared to acarbose and interacted significantly with several amino acid residues of the enzyme. Similarly, this molecule and 3,4-Dicaffeoylquinic acid demonstrated a strong affinity for α-glucosidase, suggesting their potential as natural inhibitors of enzymes involved in carbohydrate metabolism. Most of the compounds are not substrates of P-glycoprotein and exhibit high intestinal absorption. Furthermore, the majority of these compounds do not act as inhibitors or substrates of CYP450 enzymes, reinforcing their suitability for development as oral medications. These results underscore the potential of immature carob pulp as a promising antidiabetic agent.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol and proteins. In re-sponse to cell stimulation or injury, metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahex-aenoic acid from the sn-2 position of glycerol moiety by the action of phospholipases A2. Ara-chidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotri-enes, and thromboxane are also involved in cell proliferation, differentiation, and blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called as specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell pro-tective effects. Sphingolipid derived-metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hy-droxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

Glutamate transporter-1 (GLT-1) dynamics are implicated in excitotoxicity and Alzheimer's disease (AD) progression. Early stages of AD are often marked by hyperactivity and increased epileptiform activity preceding cognitive decline. Previously, we identified a direct interaction between GLT-1 and Presenilin 1 (PS1) in the brain, highlighting GLT-1 as a promising target in AD research. This study reports the significance of this interaction and uncovers a novel role of GLT-1 in modulating amyloid-beta (Aβ) production. Overexpression of GLT-1 in cells reduces the levels of Aβ40 and Aβ42 by decreasing γ-secretase activity pertinent to APP processing and induces a more "open" PS1 conformation, resulting in decreased Aβ42/40 ratio. Inhibition of the GLT-1/PS1 interaction using cell-permeable peptides produced an opposing effect on Aβ, highlighting the pivotal role of this interaction in regulating Aβ levels. These findings emphasize the potential of targeting GLT-1/PS1 interaction as a novel therapeutic strategy for AD.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development, and addresses some of the major limitations that previously hindered the development of therapies for rare diseases.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

Geological disposal facilities for radioactive waste pose significant challenges for robust monitoring of environmental conditions within the engineered barriers that surround the waste canister. Temperatures are elevated, due to the presence of heat generating waste, relative humidity varies from 20% to 100%, and swelling pressures within the bentonite barrier can typically be 2-10 MPa. Here, we test the robustness of a bespoke design MEMS sensor-based monitoring system, which we encapsulate in polyurethane resin. We place the sensor within an oedometer cell and show that despite a rise in swelling pressure to 2 MPa, our relative humidity (RH) measurements are unaffected. We then test the sensing system against a traditional RH sensor, using saturated bentonite with a range of RH values between 50% and 100%. Measurements differ, on average, by 2.87% RH, and are particularly far apart for values of RH greater than 98%. However, bespoke calibration of the MEMS sensing system using saturated solutions of known RH, reduces the measurement difference to an average of 1.97% RH, greatly increasing the accuracy for RH values close to 100%.

Aeromagnetic data coupled with Landsat ETM+ data and SRTM DEM have been processed in order to map regional hydrogeological structures in the basement complex region of Paiko, north-central Nigeria. Lineaments were extracted from derivative maps from aeromagnetic, Landsat ETM+ and SRTM DEM datasets. Ground geophysical investigation utilizing Radial Vertical Electrical Sounding (RVES) was established in nine transects comprising of four sounding stations which are oriented in three azimuths. Source Parameter Imaging (SPI) was employed to map the average depths structures from aeromagnetic dataset. Selected thematic layers which included lineaments density, lithologic, slope, drainage density and geomorphologic maps were integrated and modelled using ArcGIS to generate groundwater potential map of the area. Groundwater zones were classified into four categories: very good, good, moderate and poor according to their potential to yield sustainable water to drilled wells. Results from RVES survey reveal a close correlation to lineaments delineated from surface structural mapping and remotely sensed datasets. Hydrogeological significance of these orientations suggest that aeromagnetic data can be used to map relatively deep-seated fractures which are likely to be open groundwater conduits while remotely sensed lineaments and orientations delineated from the RVES survey may indicate areas of recharge. Regions with high lineament density have relatively better groundwater potential. This is attributable to areas having deep weathering profiles associated with intrusive bodies that have resulted in intense fracturing in the area. Drill depths in this area should target a minimum of 80 m to ensure sufficient and sustainable supplies to drilled wells. The outcome of this study should act as information framework that would guide the siting of productive water wells and while providing needed information for relevant agencies in need of data for the development of groundwater resources.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in people with HIV (PWH). Since lamivudine remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure. ART guidelines do not recommend the use of drugs impacted by resistance-associated mutations as they have been confirmed to comprise a risk factor for virological failure. However, previous authors suggest that 3TC/FTC can remain active even in the presence of M184V. Obtaining the viral resistance profile for each individual both treated or ART-naïve is a key challenge for lifelong treatment management.Given the potential benefits of lamivudine in the ART combinations, the investigation of M184V remains of high interest for clinicians and researchers. This is a review of literature for the challenges in treating both naïve and experienced individuals carrying the M184V resistance mutation, including virological failure, virological suppression, and resistance to ART.

Clinical academics experience dual workplaces; the clinical and the research environment. However, working in two workplaces leads to difficulty in forming an integrated identity, and hence affects a person’s work environment and well-being. The aim was to explore how clinical academics experience the psychosocial work environment and their suggestions for improving and changing work well-being. A multicenter qualitative approach with group interviews inspired by participatory action de-sign was used. A purposeful criterion sampling strategy was used, selecting researchers affiliat-ed with the university's research network (n=12). Data were analyzed by thematic analysis and the consolidated criteria for reporting qualitative research was applied. The main finding “lack of integration of research in clinical practice”, revealed how clinical academics balanced between the two practices, how their need for belonging in both work environments were established by fellowship, and how motivational factors and role models could be enhanced through a joint commitment of responsibility in research units and clinical practice. This study provides a contemporary understanding of the challenges that clinical academics en-counter and what solutions they would offer. This study adds to knowledge on psychological work well-being and provides solutions on how clinical academics can achieve integration of research in clinical practice.

Objective: This prospective study investigated the feasibility performing laparoscopic pelvic surgery in spinal anesthesia and analyzed their intraoperative side effects like pain and nausea and vomitus of 915 patients. Methods: Implementation and performance of laparoscopic surgery under local anes-thesia of 915 patients out of a total of 3212, who underwent laparoscopic pelvic surgery in spinal anesthesia, were analyzed in relation to BMI (Body Mass Index), obesity, pain during surgery and amount of intraperitoneal mmHg CO2 gas pressure and surgical complications. Results: BMI > 30, intraabdominal adhesions, increased duration of the operation, bleeding and increased intraperitoneal CO2 pressure were statistically significant as the main causes of pain during laparoscopic surgery in spinal anesthesia. Under-weight patients, on the other hand, had less pain when intra-abdominal pressure in-creased compared to those of normal weight. The appearance of pain, nausea and vomitus occurred in 10,3% and was easy to manage and treat. It did not affect the sur-geon's work and the course of the operation. Conclusion: In view of these observations, we are proposing spinal anesthesia for lap-aroscopic surgery as the first choice in those patients, who have no contraindications. In our knowledge this clinical study constitutes the largest clinical observations and dataset that applies spinal anesthesia in laparoscopic pelvic surgery.

The objectives of the study were to determine the spatial rate of CO₂ flux (Net Ecosystem Exchange) and soil moisture in a wetland ecosystem applying Sentinel-1 IW (Interferometric Wide) data of VH (Vertical Transmit/Horizontal Receive—cross polarization) and VV (Vertical Transmit/Vertical Receive—like polarization) polarization. In-situ measurements of carbon flux, soil moisture, and LAI (Leaf Area Index) were carried out over the Biebrza Wetland in north-eastern Poland. The impact of soil moisture and LAI on backscattering coefficient (σ°) calculated from Sentinel-1 data showed that LAI dominates the influence on σ° when soil moisture is low. The models for soil moisture have been derived for wetland vegetation habitat types applying VH polarization (R² = 0.70 to 0.76). The vegetation habitats: reeds, sedge-moss, sedges, grass-herbs, and grass were classified using combined one Landsat 8 OLI (Operational Land Imager) and three TerraSAR-X (TSX) ScanSAR VV data. The model for the assessment of Net Ecosystem Exchange (NEE) has been developed based on the assumption that soil moisture and biomass represented by LAI have an influence on it. The σ° VH and σ° VV describe soil moisture and LAI, and have been the input to the NEE model. The model, created for classified habitats, is as follows: NEE = f (σ° Sentinel-1 VH, σ° Sentinel-1 VV). Reasonably good predictions of NEE have been achieved for classified habitats (R² = 0.51 to 0.58). The developed model has been used for mapping spatial and temporal distribution of NEE over Biebrza wetland habitat types. Eventually, emissions of CO₂ to the atmosphere (NEE positive) has been noted when soil moisture (SM) and biomass were low. This study demonstrates the importance of the capability of Sentinel-1 microwave data to calculate soil moisture and estimate NEE with all-weather acquisition conditions, offering an important advantage for frequent wetlands monitoring.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, is significantly underreported in Mongolia due to geographical remoteness, lack of early diagnostics, and poor clinical management. This study aimed to provide a more accurate estimate of CE in Mongolia by comparing data of surgical (reported) and diagnosed (unreported) cases, and assessing the challenges faced by rural doctors in disease management and surveillance. We collected data on surgical cases hospitalized between 2006-2016 and newly diagnosed CE cases in 2016 from eight provinces. Using a quasi-Poisson regression model of the collected data, we used extrapolation to estimate the number of diagnosed cases for the entire country. Additionally, fourty health professionals from all 21 provinces rated local clinical management for CE through a questionnaire. Results reveal that surgical cases (2.2 per year) represent only one-eighth of diagnosed cases (15.9 per year). The laboratory facilities, disease reporting, and cyst classification usage scored below 2. These results highlight the significant underreporting of CE in Mongolia and urges human and animal health experts, along with policymakers, to invest into combating CE, particularly in remote provincial areas. It also emphasizes the need for standard clinical management involving cyst classification according to WHO-IWGE, seamless integration of CE reporting and monitoring mechanisms, which can significantly contribute to the national and global burden estimation of CE.

Glucagon-like peptide-1 (GLP-1) agonists are gaining attention as a potential treatment for obesity. While studies have shown that these medications greatly impact dietary habits, their relationship to consumer food waste is unexplored. We analyzed data from 505 U.S. consumers who self-report GLP-1 medication use and found that 25% agree that they waste more food since beginning the medication with 61% disagreeing with this statement. Respondents are less likely to agree with this statement if they have been on the medication a longer time and more likely to agree if they report experiencing nausea since beginning the medication. Several dietary changes are also significantly associated with self-reported changes in food waste since starting the medication. With previous literature finding GLP-1’s significant impact on individual food consumption and dietary choices, our findings suggest that the effects of this novel class of anti-obesity medications may cast a significant impact on food waste patterns. With the potential for widespread adoption of these medications, and given that approximately one-third of food in the United States is wasted by consumers, understanding the interaction of these two consumer trends is critical for projecting their joint impact on the food system.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. The Random Forest algorithm correctly identified 83% of polygon pixels reserved for testing. The developed workflow relied solely on open source software and acquired ground observations. Space organization was directed by the altitude as shown by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 demonstrates some trends of vegetation cover evolution in response to climate change in the considered area. The potential applications in terms of permafrost modeling (hiperborea.omp.eu) are finally discussed.

Gastrotricha are microscopic benthic animals found in almost all water bodies. To date, about 870 species distributed in 71 genera, 18 families, and two orders are known. Known freshwater species are 359, several of which found also in Italy; however, a compendium of the studies carried out so far and a georeferenced distribution of the species still needs to be provided. This project aims to summarize information about Italian gastrotrichs' diversity and geographic distribution. Diversity data, acquired over 239 years, were reviewed and corrected based on taxonomic and nomenclatural updates and, in addition to distribution information, were organized into a data matrix useful for statistical analysis and to be feed to a Geographic Information System software to easily understand the overall figures. Results indicate Italy as one best-known country regarding freshwater gastrotrich, with 88 species in 16 genera and 3 families from 59 investigated localities; the Nation counts 16 type localities and 19 endemic species. Despite its censed biodiversity, many Italian regions remain still poorly or not investigated where future research should focus. Implementing a web mapping plugin enabled the creation of interactive maps for an easy and modern sharing of the work done and information acquired.

The aim of this study is to analyse problems related to thermal mapping obtained from thermal data acquired from Unmanned Aerial Systems (UAS) equipped with thermal cameras. We focused on an accurate analysis of uncertainties introduced by the PIX4D Mapper software used to obtain the surface temperature maps of thermal images acquired by the UAS. To achieve this aim, we used artificial thermal reference during the surveys, as well as natural hot targets, i.e. thermal anomalies in the Pisciarelli hydrothermal system in Campi Flegrei caldera (CFc). Artificial thermal targets, expressly created and designed for this goal, are a prototype here called “developed thermal target” (DTT) made by the drone Laboratory at Istituto Nazionale di Geofisica e Vulcanologia - Osservatorio Vesuviano (INGV-OV). We show the results obtained by three surveys during which thermal targets were positioned on land at different flight heights of the UAS. Different heights were also necessary to test spatial resolution of the DTT with the used thermal camera as well as possible temperature differences between the raw images acquired by UAS with the thermal mapping obtained from the PIX4D Mapper software. In this work we have estimated the uncertainty that may be introduced by the mosaic procedure and furthermore we find an attenuation of the measured temperatures introduced by the different distances between the thermal anomaly and sensor. These results appear to be of great importance for the subsequent calibration phase of the thermal maps especially in cases where these methodologies are applied for monitoring purposes of volcanic/geothermal areas.

This communication is to summarize our single center experience on applications of anti-IL-1 biologic response modifiers on autoimmune and autoinflammatory conditions in children. We present our rationale for off-label utilization of Anakinra and discuss evolving treatment paradigms that warrants further research and validation. Based on our observations and successful treatment outcomes, we advocate future multilateral efforts to liberate access to anti-IL-1 medications to control inordinate and detrimental inflammation in children.

In contemporary narratives, the rural and regional identities of a place, as judged by its inhabitants’ sense of belonging, continue to be important points that need to be (re)considered when discussing places as instruments for local development. This paper pushes forward these debated and explores the construction of rural and regional identity in Romania with the help of a case study that focuses on two rural communities situated on opposite sides of the river Mureș. Based on participant and ethnographic observation and making use of a qualitative analysis, this paper highlights the most significant features of the local cultural identities expressed by the two sets of people, which often coincide with the most important characteristics attributed to the regions separated by the river Mureș. The results of this study underline the dividing role of a river in the preservation of rural and regional identity. They also demonstrate that rural identity construction along the river has generated both rural development opportunities and various risks.

(1) Background: With the United Nations Sustainable Development Goals (SDG) (2015-2030) fo-cusing on reducing maternal mortality, monitoring and forecasting Maternal Mortality Rates (MMR) in regions like Africa become crucial for health strategy planning by policymakers, in-ternational organizations, and NGOs. (2) Methods: We collected maternal mortality rates per 100,000 births from the World Bank database between 1990 and 2015. Join Point regression was applied to assess trends, and the autoregressive integrated moving average (ARIMA) model was used on 1990-2015 data to forecast the MMR for the next 15 years. (3) Results: The study found a decline in MMR in Africa with an average annual percentage change (APC) of -2.6% (95% CI -2.7; -2.5). North Africa reported the lowest MMR, while East Africa experienced the sharpest decline. The region-specific ARIMA models predict that the maternal mortality rate (MMR) in 2030 will vary across regions, ranging from 65 deaths per 100,000 births in North Africa to 249 deaths per 100,000 births in Central Africa., averaging 197 per 100,000 births for the continent. (4) Conclusions: Despite the observed decreasing trend in maternal mortality rate (MMR), the MMR in Africa remains relatively high. The results indicate that MMR in Africa will continue to decrease by 2030. However, only North and South Africa will likely reach the SDG target.

Multisource meteorological re-analyses are the most reliable forcing data for driving hydrological models to simulate streamflow. We aimed to assess the different hydrological responses through hydrological modeling in the upper Lancang-Mekong River Basin (LMRB) using the two gridded meteorological datasets, climate forecast system reanalysis (CFSR) and the China Meteorological Assimilation Driving Datasets for the SWAT model (CMADS). We selected the Pearson’s correlation coefficient (R), percent bias (PBIAS), and root mean square error (RMSE) indices to compare the six meteorological variables of the two datasets. The spatial distributions of the statistical indicators in the CFSR and CMADS, namely, the R, PBIAS, and RMSE values, were different. Furthermore, the soil and water assessment tool plus (SWAT+) model was used to do hydrological modeling based on CFSR and CMADS meteorological re-analyses in the upper LMRB. Different meteorological datasets resulted in significant differences of hydrological responses, which reflected by different sensitive parameters and their optimal value. These different calibrated optimal values of sensitive parameters further lead to the different simulated water balance components between CFSR- and CMADS-based SWAT+ model. These findings can help in a better understanding of the strengths and weaknesses of different meteorological re-analysis datasets and the roles on the hydrological modeling.

It is important for enterprises to decide their environmental policies after carefully examining their future paths based on the relationship between the environment and the economy. This study focused on Japanese minimum administrative divisions (municipalities) and attempted to quantify the annual environmental efficiency of production activities within each division according to the theory of life-cycle impact assessment (LCIA). This study leverages the assessment theory LIME2, which is an endpoint-type LCIA method developed in 2010 that integrates environmental loads for certain impact categories, such as global warming and land use into a simple indicator by monetary unit. First, annual environmental impact assessments were conducted for all Japanese municipalities based on statistical information that was reliable, verifiable, and comparable. Next, the environmental efficiency of productivity for each division was conceptualized by dividing the gross domestic product by the environmental damage amounts as calculated above. Assessment results for each municipality were placed on a map of Japan in order to visualize the regionality of each indicator. The findings revealed in this study will aid public administrators in their decision-making process with respect to environmental policies.

The quantile estimation of extreme wind speed is needed in various environmental fields such as climatology, design of structures, renewable energy sources and agricultural operations. These calculations are crucial for the coding of wind speed. In this study, the required wind speed series of 16 stations in Khyber Pakhtunkhwa, Pakistan, was obtained from the NASA official website and measured in meters per second (m/s) at a 10-meter distance. A Regional Frequency Analysis of 16 AMWS stations was performed using L-moments. The quantile estimates of extreme wind speed are needed for various areas of interest using Regional Frequency Analysis (RFA) and extreme value theory. These calculations are crucial for the coding of wind speed. The data was taken from the NASA official website at a 10-meter distance and measured in meter per second (m/s). A Regional Frequency Analysis of AMWS using L-moments is performed utilizing wind speed data from sixteen sites (16) in Pakistan's Khyber Pakhtunkhwa province. There are no sites that are found to be discordant. The wards method is used to construct a homogenous region and make two homogenous regions from 16 sites. The heterogeneity test justifies that both clusters are homogeneous. The most appropriate probability distribution from the Generalized Normal (GNO), Generalized Logistic (GLO), Pearson Type-3 (P3), Generalized Pareto (GPA), and Generalized Extreme Value (GEV) distributions are chosen to calculate regional quantiles. According to the L-moments diagram and Z statistics, GEV for Cluster- Ι and GLO for Cluster- ΙΙ are the best suggestions from the others. Both clusters’ robustness is measured utilizing Relative Bias (RB) and Relative Root Mean Square Error (RRMSE). Overall, GEV distribution is fit for cluster-Ι, and the GLO distribution is fit for cluster-ΙΙ. Utilizing the site mean and median as index parameters, we can also find at-site quantiles from regional quantiles. The study’s quantile estimates can be employed in codified structural designs with policy consequences.

This study proposed a spatially and temporally improving methodology adopting the Regional Frequency Analysis with L-moments approach to estimate rainfall quantiles from 22787 grids of radar rainfall in Taiwan for a 24-hour duration. Due to limited radar coverage in the eastern region, significant discordant grids were found in the coastal area of the eastern region. A K-means cluster analysis using scaled at-site characteristics was used to group the QPESUMS grids in Taiwan into 22 clusters/sub-regions based on their characteristics. Spatially, homogeneous subregions with QPESUMS data produce more detailed homogeneous subregions with clear and continuous boundaries, especially in the mountain range area where the number of rain stations is still very limited. According to the results of z-values and L-moment ratio diagrams, the Wakeby (WAK), Generalized Extreme Value (GEV), and Generalized Pareto (GPA) distributions of rainfall extremes fitted well for the majority of subregions. The Wakeby distribution was the dominant best-fitted distribution, especially in the central and eastern regions. The east of the northern part and southern part of Taiwan had the highest extreme rainfall for each return period. Both areas were frequently struck by typhoons. By using grid-based (at-site) as the basis for assessing regional frequency analysis, the results show that the regional approach in determining extreme rainfall is very suitable for large-scale applications and even better for smaller scales such as watershed areas. The spatial investigation was performed by establishing regions of interest in small subregions across the northern part. It showed that regionalization was correct and consistent.

Ombrian curves, i.e. curves linking rainfall intensity to return period and time-scale, are well-established engineering tools, crucial to the design against storm waters and floods. Whereas at-site construction of such curves is considered a standard hydrological task, it is a rather challenging one when large regions are of interest. Regional modelling of ombrian curves is particularly complex due to the need to account for spatial dependence together with the increased variability of rainfall extremes in space. We develop a framework for the parsimonious modelling of the extreme rainfall properties at any point in a given area. This is achieved by assuming a common ombrian model structure except for a spatially varying scale parameter which is itself modelled by a spatial smoothing model for the 24 h average rainfall maxima that employs elevation as an additional explanatory variable. The fitting is performed on the pooled all-stations data using an advanced estimation procedure (K-moments) that allows both for reliable high-order moment estimation and simultaneous handling of space-dependence bias. The methodology is applied in the Thessaly region, a 13 700 km2 water district of Greece characterized by varying topography and hydrometeorological properties.

The desert locust remains a major threat to global food security. Control operations are a crucial tool to manage crisis; this research investigated the nature of control operations conducted between 2019-2021. Historical data on desert locust and control operations were obtained from the survey reports at the FAO Locust Hub and analysed with respect to survey reports, land cover types, cropland/rangeland extent and crop productivity data. We found that 16.1% of the grid cells with locust presence and 14.9% of the grid cells with control operations had a proportion of rangeland higher than 0.75; while 13.3% of the grid cells with locust presence and 13.2% of the grid cells with control operations had a proportion of croplands higher than 0.75, highlighting that locust presence and control operations were reported in both rangeland and cropland. Control operations continue to be used both to reduce overall locust numbers and to protect crops. Furthermore, through identifying which crops were most at risk, our analyses indicate that wheat production was under the highest strain during periods of increased locust infestations.

Based on the theory that certain geological fault zones surpass the influence of other abiotic and biotic site factors for mound-building red wood ants (Formica rufa group), an area northwest of Tuttlingen with extremely high ant density was systematically surveyed, taking into account official geological maps. Indicators of active fault zones were recorded. These were additionally examined in a model area using a high-resolution digital terrain model (DTM 1-meter). The study area is located in the Swabian Jura at the western edge of the Albstadt shear zone, where recent seismic activity is documented by frequent earthquakes. The earthquakes are considered to be the cause of gas permeability in the strike-slip faults, around which the clustered nesting sites were mapped. More than 2900 nests of the Formica rufa group were mapped and their site conditions analysed in different geomorphological positions. In addition to recording forestry site conditions, a geological classification was carried out, as well as an analysis of soil gases/mofettes in areas with the highest nest densities. The correlation between forestry data and nest sites did not reveal a consistent pattern. In contrast, the relationships with gas-permeable strike-slip faults, though predominantly covered with Quaternary sediments, could be identified through CO₂- and CH₄-rich gas emissions, mofettes, and doline features. The interpretations were complicated due to different mapping ages and signatures of the geological maps. Fortunately, this issue could be analysed and evaluated in a sub-area with mappings from 1936/71 and 1995 regarding presumed or confirmed fault trajectories. New insights were gained regarding the relationships between Formica nest sites, gas-permeable faults, and groundwater levels on narrow mountain ridges with steep relief. Here, the lateral emission of CO₂ depends on the groundwater level and does not occur vertically directly above the fault. C- and H-isotope data of CO₂ and CH₄ do not show a consistent source. While methane is mainly derived from biological production by Archaea in the upper crust and in swamp areas, CO₂ mostly originates from the mantle. The results of the investigations revealed that a multitude of geological and ecological factors must be considered for the interpretation of the occurrences of Formica sites northwest of Tuttlingen. These factors confer a distinct originality to this region, contributing not only to an enhanced understanding of site conditions but also furnishing information regarding environmentally relevant gas emissions.

Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Long COVID-19 affects a significant percentage of survivors and is characterized by a wide range of symptoms, including weariness and mental fog as well as emotional symptoms like worry and sadness. COVID-19 is closely linked to the autoimmune disorders that are becoming more prevalent worldwide and are linked to the immune system hyperactivation, neutrophil extracellular trap (NET) development, and molecular mimicry pathways. Long-term COVID-related autoimmune responses include a watchful immune system, altered innate and adaptive immune cells, autoantigens secreted by living or dead neutrophils, and high concentrations of autoantibodies directed against different proteins. The microbiome, which consists of billions of bacteria living in the human body, is essential for controlling immune responses and supporting overall health. The microbiome can affect the course of long-term COVID-associated autoimmunity, including the degree of illness, the rate of recovery, and the onset of autoimmune reactions. Although the precise role of the microbiome in long COVID autoimmunity is still being investigated, new studies indicate that probiotics, prebiotics, and dietary changes—interventions that target the microbiome—may be able to reduce autoimmune reactions and enhance long-term outcomes for COVID-19 survivors. It is clear that more research is required to precisely understand how the microbiome affects COVID-19-related autoimmunity and to create tailored treatment plans.

The organic material present at the same depth in the reservoir has the potential for conversion, as indicated by analyses conducted before and after combustion in the development of heavy oil. This paper examines the oxidation and pyrolysis reaction pathways of hydrocarbons, specifically benzaldehyde (C₇H₆O) and naphthalene (C₁₀H₈), before and after combustion using molecular dynamics simulations. The primary products formed under various temperature conditions include H₂O, HO₂, CO, and CO₂. The discussion includes the number of molecules, such as HO and H, as well as their temperature variations. The activating group functions as an electron donor, while the inactivating group serves as an electron acceptor. The oxidation and pyrolysis reactions of naphthalene and the synthesis pathway of benzaldehyde are also explored. The C-C dissociation pathway in the early stages of combustion and the process of C-C bond synthesis in the later stages of the reactions are investigated through dynamic simulations at different temperatures: 3000 K, 3500 K, and 4000 K, with a particular focus on the reaction network at 4000 K. The application of the molecular reaction dynamics method to heavy oil combustion research is the primary objective of this work. This study aims to provide a novel approach to investigating hydrocarbon conversion at high temperatures and offers recommendations for enhanced oil recovery.

This study examines the relationship between Gross Domestic Product (GDP) and income inequality in Greece across three key periods: the pre-crisis period (2003-2008), the crisis and memoranda period (2009-2014), and the post-crisis period (2015-2020). Using data from the World Bank Open Data database, the study employs correlation analysis, and linear regression models to analyze how economic changes influence income distribution. The findings reveal that during the pre-crisis period, economic growth was moderately correlated with increasing inequality, although this relationship was not statistically significant, indicating uneven distribution of growth benefits. In the crisis period, a strong and statistically significant negative relationship between GDP and the Gini coefficient was identified, highlighting the sharp rise in inequality as the economy contracted due to austerity measures. In the post-crisis period, the relationship between GDP and inequality weakened, showing a statistically insignificant correlation, suggesting that economic recovery alone did not significantly reduce inequality. The study concludes that economic growth is insufficient to address income inequality without targeted policy interventions, particularly during periods of crisis. These findings underscore the importance of comprehensive social policies to mitigate inequality and suggest areas for future research on the impact of specific interventions on income distribution.

Prosthechea karwinskii is an orchid endemic to Mexico, threatened by the destruction of its habitat and the extraction of specimens to meet its demand for ornamental and religious use. Most of its populations, and the most locally abundant ones, are found in Oaxaca state. Variations in some floral traits have been observed in these populations. We implemented a morphometric analysis to assess their floral variation and identify the most significant characters in the morphological patterns of this orchid. Floral samples were collected from 17 populations of P. karwinskii in Oaxaca, as well as from specimens used as ornaments during Easter in a Oaxacan community (Zaachila), whose origin is unknown. Sampling of natural populations covered the environmental, geographic and morphological variation of the species. We performed an analysis of variance (ANOVA), principal component analysis (PCA), and canonical variate analysis (CVA), and cluster analysis including 185 individuals and 45 variables (13 of them were discarded in the multivariate analyzes due to high correlation). Characters of the column, lateral sepal, and labellum were most informative about the observed morphological patterns. Albarradas showed the greatest morphological differentiation, mainly due to the column. In general, individuals from the same locality tended to overlap more, especially the populations of Jaltianguis and Yahuiche, which were different from the geographically close population of Etla. Teposcolula presented the highest values in perianth characters, unlike Sola_Rancho Viejo. The specimens recovered from religious ornaments were morphologically more similar to those from the Mixtec region and surroundings of Etla. Our work encourages working on collaborative conservation strategies to ensure the long-term permanence of both the species and its traditional uses.

Dendritic cells (DCs) are the most specialized antigen-presenting cells and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs) i.e. immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature- and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumor, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumor and metastatic LNs compared to non-metastatic LNs. Cases which showed a high infiltration of S100-DCs in metastatic LNs appeared to show a favorable prognosis although statistical significance was not reached. In the RT/CRT group, infiltration of CD1a-DCs and S100-DCs were fewer in the primary tumor and metastatic LNs compared to the treatment naive group. Conversely, the RT/CRT group showed higher CD1a-DCs and S100-DCs numbers in non-metastatic LNs compared to the treatment naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.

Understanding the distribution of rock glaciers provides key information for investigating and recognizing the status and changes of the periglacial environment. Deep learning algorithms and red-green-blue (RGB) bands from high-resolution satellite images have been extensively employed to map rock glaciers. However, the near-infrared (NIR) band offers rich spectral information and sharp edge features that could significantly contribute to semantic segmentation tasks, but it is rarely utilized in constructing rock glacier identification models due to the limitation of three input bands for classical semantic segmentation networks, like DeeplabV3+. In this study, a dual-encoder DeeplabV3+ network (DEDNet) was designed to overcome the flaws of classical DeeplabV3+ network (CDNet) when identifying rock glaciers using multispectral remote sensing images by extracting spatial and spectral features from RGB and NIR bands, respectively. This network, trained with manually labeled rock glacier samples from QiLian Mountains, established a model with accuracy, precision, recall, specificity, and mIoU (Mean Intersection over Union) of 0.9131, 0.9130, 0.9270, 0.9195, and 0.8601, respectively. The well-trained model was applied to identify new rock glaciers in a test region, achieving a producer's accuracy of 93.68% and a user's accuracy of 94.18%. Furthermore, the model was employed to two study areas in northern Tien Shan (Kazakhstan) and Daxue Shan (Hengduan Shan, China) with high accuracy, which proved that the DEDNet offers an innovative solution to more accurately map rock glaciers on a larger scale due to its robustness across diverse geographic regions.

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at King Khalid hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii has occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019 the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high resistant proportion of ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.

Pigeon paramyxovirus serotype 1 (PPMV-1), primarily originating from racing pigeons, has become a global panzootic, spreading to poultry and wild birds, thus posing a threat to the poultry industry. Egypt uses both inactivated pigeon paramyxovirus (PPMV-1) and conventional Newcastle disease virus (NDV) vaccines to protect pigeons. However, the impact of prevalent strains and the effectiveness of available vaccines in pigeons in Egypt are unclear. This study investigates the virulence of PPMV-1 isolated from vaccinated pigeons in Sharkia, Egypt (Pigeon/ Egypt/Sharkia-19/2015/KX580988). Ten-day-old specific-pathogen-free embryonated chicken eggs infected with this strain exhibited a mean death time (MDT) of 86.4±5.88 hours. The intracerebral pathogenicity index (ICPI) in day-old chicks was 0.8, while pigeons experienced an ICPI of 0.96 and an intravenous pathogenicity index (IVPI) of 2.11. These findings classify the strain as virulent and velogenic. Experimental infection with this PPMV-1 strain at 106 EID50/0.1 ml resulted in a 62.5% mortality rate in pigeons, displaying nervous and enteric distress. The virus caused extensive lesions in visceral organs, with strong immunohistochemistry signals in all examined organs, indicating the systemic spread of the virus concurrent to its neurotropic and viscerotropic tropism. Furthermore, vaccination using inactivated PPMV-1 and live NDV LaSota vaccine regimen protected 100% of pigeons against mortality, while a single NDV LaSota vaccine provided 62.5% protection. The PPMV alone or combined with NDV LaSota induced protective levels of hemagglutination inhibition antibody titers and reduced virus shedding from buccal and cloacal cavities. These findings suggest that using both inactivated PPMV-1 (G-VI) and live attenuated NDV (LaSota) vaccines is an effective prophylactic regimen for preventing and controlling PPMV-1 and NDV in pigeons, thereby reducing the risk of interspecies transmission.

Shrimp is the most important aquaculture industry. Therefore, we determined the effect of nitrifying-probiotic bacteria on water quality, growth, survival, immune response and intestinal microbiota of Litopenaeus vannamei cultured without water exchange. In vitro, only B. licheniformis used TAN, nitrites and nitrates since nitrogen bubbles were produced. TAN decreased significantly in the treatments with bacilli and LAB, but no differences were observed in nitrites. Nitrates were significantly higher in the treatments with bacteria. The final weight and survival of shrimp in the bacterial treatments increased significantly and superoxide anion increased significantly only in LAB treatment. The activity of phenoloxidase decreased significantly in the treatment with LAB and with the mixture of bacilli and LAB. Shrimp treated with bacilli in the water showed lower species richness. The gut bacterial community after treatments was significantly different from that of the control. Linoleic acid metabolism was positively correlated with final weight and superoxide anion, whereas quorum sensing was correlated with survival. Thus, bacilli and LAB in the water of hyperintensive culture systems act as nitrifers, modulate the intestinal microbiota and immune response, and improve the growth and survival of shrimp. This is the first report on Pediococcus pentosaceus and Leuconostoc mesenteroides as nitrifying bacteria.

Plant height is significantly correlated with grain traits, which is a component of wheat yield. The purpose of this study is to investigate the main QTLs that control plant height and grain-related traits in multiple environments. In this study, we constructed a high-density genetic linkage map using the Wheat50K SNP Array to map quantitative trait loci (QTLs) for these traits in 198 recombinant inbred lines (RILs). The two ends of the chromosome were identified as re-combination-rich areas in all chromosomes except chromosome 1B. The middle area of the chro-mosomes was identified as the recombination-barren area. Both the genetic map and the physical map showed a significant correlation when p=0.001, with a correlation coefficient between 0.63 and 0.99. However, there was almost no recombination between 1RS and 1BS. In terms of plant height, 1RS contributed to the reduction of plant height by 3.43cm. In terms of grain length, 1RS contributed to the elongation of grain by 0.11mm. A total of 43 QTLs were identified, including 8 QTLs for Plant height(PH), 11 QTLs thousand grain weight(TGW), 15 QTLs for grain length(GL),and 9 QTLs for grain width(GW), which explained 1.36%–33.08% of the phenotypic variation. Seven were environment-stable QTLs, including two loci Qph.nwafu-4B and Qph.nwafu-4D that determined plant height. The explanation rates of phenotypic variation were 7.39%-12.26% and 20.11%-27.08%, respectively. One QTL, Qtgw.nwafu-4B, which influenced TGW, showed an explanation rate of 3.43%-6.85% for phenotypic variation, two co-segregating KASP markers were developed, the physical locations corresponding to KASP_AX-109316968 and KASP_AX-109519968 were 25.888344 MB and 25.847691 MB. Another QTL, Qgw.nwafu-4D, which determined grain width, had an explanation rate of 3.43%-6.85%. Three loci that affected the grain length were Qgl.nwafu-5A, Qgl.nwafu-5D.2 and Qgl.nwafu-6B, illustrating the explana-tion rates of phenotypic variation as 6.72%-9.59%, 5.62%-7.75%, and 6.68%-10.73%, respectively. Two QTL clusters were identified on chromosomes 4B and 4D.

Since the 1960s, the countries of sub-Saharan Africa have been affected by an urban crisis due to the demographic explosion in cities and the resulting land pressures. These have resulted in the proliferation of spontaneous housing areas which question the future of urban vegetation and its degree of inclusion in city planning. To analyze the state of knowledge on the research already carried out on the development of urban landscape, particularly in sub-Saharan Africa, a literature review on urban forestry covering the period 1998-2022 was carried out in order to better orient future research works for a greater consideration to urban forestry and their contributions in combating the adverse effects of climate change. Out of a set of 110 scientific papers selected, 50 were considered relevant because of their direct link with urban forestry. From the analysis of this papers, a classification of the articles according to 05 themes was carried out. These are: management of green spaces in urban areas, functions of trees in an urban environment, development of urban forestry, characterization of urban tree flora and financing of urban forestry. Thus, “function of trees in an urban environment and the characterization of urban tree flora” are the most addressed respectively at 42% and 28%. “Financing urban forestry” is practically not addressed (2%). The analysis of the 50 selected articles reveals a significant geographic concentration of urban forestry research. Countries like South Africa, Kenya, and Ghana are more represented in the literature, while vast regions in Central and Western Africa (e.g., Democratic Republic of Congo, Chad, and Niger) have minimal or no documented research on urban forestry. Future research should address these underrepresented themes, as they are crucial for the long-term sustainability of urban forestry projects. Particularly, research on financing mechanisms is essential to unlock sustainable funding sources for urban forestry, a critical barrier to its expansion.

Levels of trace element pollution in surface soil can be estimated using soil analyses and leaching tests. These methods may reveal different results due to the effect of soil properties, such as grain size and mineral composition, on elemental availability. Therefore, this study advocates an alternative method for monitoring and assessment of trace element pollution in surface soil using terricolous fruticose lichens. Lichens growing at abandoned mine sites and unpolluted areas in southwest Japan and their substrata were analyzed using inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry to clarify the relationships between Cu, Zn, As, and Pb concentrations in lichens and soils, including their absorption properties. Concentrations of these elements in the lichens were positively correlated with those in the soils regardless of lichen species, location, habitat, or conditions of soils. The analyzed lichens had neither competitive nor antagonistic properties in their elemental absorption, which made them good biomonitors of trace element pollution in surface soil. The distribution maps of average Cu, Zn, As, and Pb concentrations at each sampling region detected almost all of the Cu, Zn, and As pollution of the soils. Therefore, lichens could be used in practical applications to monitor Cu, Zn, and As pollution in surface soils.