The ongoing COVID-19 pandemic still threatens human health around the world. The methyltransferases (MTases) of SARS-CoV-2, specifically nsp14 and nsp16, play crucial roles in the methylation of the N7 and 2′-O positions of viral RNA, making them promising targets for the development of antiviral drugs. In this work, we performed structure-based virtual screening for nsp14 and nsp16 using the screening workflow (HTVS, SP, XP) of Schrödinger 2019 software, and we carried out biochemical assays and molecular dynamics simulation for the identification of potential MTase inhibitors. For nsp14, we screened 239,000 molecules, leading to the identification of three hits A1–A3 showing N7-MTase inhibition rates greater than 60% under a concentration of 50 µM. For the SAM binding and nsp10-16 interface sites of nsp16, the screening of 210,000 and 237,000 molecules, respectively, from ZINC15 led to the discovery of three hit compounds B1–B3 exhibiting more than 45% of 2′-O-MTase inhibition under 50 µM. These six compounds with moderate MTase inhibitory activities could be used as novel candidates for the further development of anti-SARS-CoV-2 drugs. Full article

The universal newborn hearing screening (NHS) program was implemented in Russia in 2008 to replace the high-risk newborn hearing screening. More than 95% coverage and significant improvement in early detection and intervention is achieved. Meanwhile, it was shown that current OAE-based hearing screening missed 13% of newborns with genetically ascertained hereditary sensorineural hearing loss (SNHL). The aim of the study is to assess the results of genetic investigation and NHS in a large cohort of Russian children with bilateral SNHL and to study the feasibility of implementation of combined hearing and genetic screening in Russia. Genetic, audiological and NHS data of 1292 pediatric patients with bilateral SNHL born in 2008–2021 were analyzed. GJB2 sequencing was performed for all subjects, 644 patients had pathological GJB2 genotype, 406 of them were homozygous for c.35delG variant. The group of 155 GJB2-negative patients were searched for other SNHL genes, The pathological genotypes were identified at 87 patients. The most frequent genes were STRC (21.8%), USH2A (16.1%), OTOF (8%) and SLC26A4 (6.9%). Children with confirmed genetic etiology passed NHS in 21% of cases. The perspectives of implementation of national comprehensive newborn hearing and genetic screening including whole exome sequencing technologies are discussed. Full article

The purpose of this study was to investigate nutrition perspectives, basic nutrition knowledge, and preferred sources of nutrition information among students at a southwestern university in the US. An original online survey was used to evaluate common sources of nutrition information, factors viewed as comprising a healthy dietary pattern, and attitudes toward nutrition information and recommendations. A total of 316 participants completed the survey. Prioritizing fruits and vegetables was the most common response (97%) for characterizing healthy eating. When asked which factors characterize a non-healthy pattern of eating, eating sweets was the top response (83%). The most common sources of nutrition information reported were word of mouth/friends and family (56%), followed by social media (45%). The majority felt that nutrition recommendations are constantly changing (78%) and that nutrition information is confusing (55%). Our data indicate that most students rely primarily on informal sources of nutrition information. However, our preliminary data also suggest that many students have a fair understanding of basic principles of healthy eating. More research in a broader and more diverse sample is needed to validate these findings. Full article

The use of artificial water points for wildlife in African savannah ecosystems has been widely criticised for affecting the distribution of wildlife and initiating changes in the heterogeneity of natural landscapes. We examined the spatiotemporal variations in the landscape before and after the installation of an artificial water point by integrating the analysis of vegetation and soil spectral response patterns with a supervised learning random forest model between 2002 and 2022 in Chobe Enclave, Northern Botswana. Our results revealed that the study area is characterised by animal species such as Equus quagga, Aepyceros melampus, and Loxodonta africana. The findings also showed that the main vegetation species in the study area landscape include Combretum elaeagnoides, Vachellia luederitzii, and Combretum hereroense. The artificial water point induced disturbances on a drought-vulnerable landscape which affected vegetation heterogeneity by degrading the historically dominant vegetation cover types such as Colophospermum mopane, Dichrostachys cinerea, and Cynodon dactylon. The immediate years following the artificial water point installation demonstrated the highest spectral response patterns by vegetation and soil features attributed to intense landscape disturbances due to abrupt high-density aggregation of wildlife around the water point. Landscapes were strongly homogenised in later years (2022), as shown by overly overlapping spectral patterns owing to an increase in dead plant-based material and senescent foliage due to vegetation toppling and trampling. The landscape disturbances disproportionately affected mopane-dominated woodlands compared to other vegetation species as indicated by statistically significant land cover change obtained from a random forest classification. The woodlands declined significantly (p < 0.05) within 0–0.5 km, 0.5–1 km, 1–5 km, and 5–10 km distances after the installation of the water point. The results of this study indicate that continuous nonstrategic and uninformed use of artificial water points for wildlife will trigger ecological alterations in savannah ecosystems. Full article

While Paul Holloway’s scholarship on Philippians has been important, his classification of Philippians as a letter of consolation has gained relatively little traction. Interestingly, however, Holloway follows Karl Barth in labelling a large section of the letter, Phil 1:27–2:16, a ‘hortatory digression’, which could be seen to diminish the extent of consolation in this part of the letter. In this article, I seek to develop Holloway’s work to argue that the Christ encomium in Phil 2:6–11 has elements of consolatory discourse that relates to other parts of the letter. Phil 2:6–11 illustrates and exemplifies how comfort (παράκλησις), consolation (παραμύθιον), and joy (χαρά) can be derived by individuals and communities in the face of opposition or destitution (cf. Phil 1:27–2:4). I propose that Christ undergoes a form of voluntary desolation in 2:6–8 but then receives something different from consolation in his glorious exaltation and the bestowal of the divine name. Although Paul and the Philippians will not receive universal worship like Christ, they can imitate him by following in this trajectory of becoming like God, thus receiving divine consolation and transformation. Full article

This paper presents an experimental investigation conducted to determine the influence of parameters such as the ambient temperature, pollution level, and substrate material on the formation of dry bands on polluted layers. To investigate these parameters, we applied a simplified insulator geometry, developed in our previous work, to experimentally control the complex process of dry band formation on a polluted surface. The simple geometry of the experimental model enabled the use of Plexiglas, RTV, and glass as construction substrate materials. RTV and glass were used to simulate a composite and ceramic insulator surface, respectively. Moreover, an electrooptic (EO) probe enabled the measurement of the axial E-field evolution at the surface of the dry band during dry band formation. The results indicated that the substrate material, ambient temperature, and pollution level substantially influence dry band formation. The effects of the first two parameters are directly associated with heat transfer phenomena in the substrate material and at the ambient air/substrate interface. The effect of the third parameter is associated with absorption and evaporation of the pollution layer. In addition, the appearance of the dry band can be clearly identified by a rapid increase in both the pollution layer resistance and the axial E-field in the dry band area. The value of the axial E-field is influenced primarily by the width of the dry band and by the pollution layer resistance, which is directly dependent on the humidification duration. Finally, because most of the results obtained herein were in accordance with those in the literature, we conclude that the proposed experimental model may provide an effective and inexpensive testing method for developing new materials and solutions for improving the dielectric performance of insulators used in polluted environments. Similarly, the simple geometry of the experimental model and the ability to easily control the experimental parameters may enable this tool to validate the results of various numerical models in studies of the thermoelectrical behavior of polluted insulators. Full article

Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus Plasmodium and is transmitted by female Anopheles mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by Plasmodium falciparum, followed by P. vivax. Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city. Full article

Unidirectional porous hydroxyapatite (UDPHAp) was developed as a remarkable scaffold characterized by a distinct structure with unidirectional pores oriented in the horizontal direction and connected through interposes. We evaluated the radiographic changes, clinical outcomes, and complications following UDPHAp implantation for the treatment of bone tumors. Excellent bone formation within and around the implant was observed in all patients treated with intralesional resection and UDPHAp implantation for benign bone tumors. The absorption of UDPHAp and remodeling of the bone marrow space was observed in 45% of the patients at a mean of 17 months postoperatively and was significantly more common in younger patients. Preoperative cortical thinning was completely regenerated in 84% of patients at a mean of 10 months postoperatively. No complications related to the implanted UDPHAp were observed. In a pediatric patient with bone sarcoma, when the defect after fibular resection was filled with UDPHAp implants, radiography showed complete resorption of the implant and clear formation of cortex and marrow in the resected part of the fibula. The patient could walk well without crutches and participate in sports activities. UDPHAp is a useful bone graft substitute for the treatment of benign bone tumors, and the use of this material has a low complication rate. We also review and discuss the potential of UDPHAp as a bone graft substitute in the clinical setting of orthopedic surgery. Full article

Many plant materials in nature have the ability to change their shape to respond to external stimuli, such as humidity or moisture, to ensure their survival or safe seed release. A well-known example for this phenomenon is the pinecone, which is able to open its scales at low humidity due to the specific bilayer structures of the scale. Inspired by this, we developed a novel humidity-driven actuator based on paper. This was realized by the lamination of untreated paper made from eucalyptus fibers to a paper–carboxymethyl cellulose (CMC) composite. As observed, the hygroexpansion of the composite can be easily controlled by the amount of CMC in the impregnated paper sheet, which, thus, controls the morphologic deformation of the paper bilayer. For a more detailed understanding of these novel paper soft robots, we also studied the dynamic water vapor adsorption, polymer distribution and hygroexpansion of the paper–polymer composites. Finally, we applied a geometrically nonlinear finite element model to predict the bending behavior of paper bilayers and compared the results to experimental data. From this, we conclude that due to the complexity of structure of the paper composite, a universal prediction of the hygromorphic behavior is not a trivial matter. Full article

This research paper investigates the potential of FinTech solutions in promoting sustainable finance in Mongolia, an emerging market economy with a burgeoning FinTech landscape. This study explores how Mongolia leverages FinTech innovations to advance sustainable development goals. Utilizing secondary data sourced from Mongolian government agencies, global financial organizations, academic institutions, market research firms, and industry associations, we conducted an integrated SWOT-MLP analysis of Mongolia’s FinTech industry, which includes the FinTech business models, ecosystem, regulatory frameworks, traditional financial institutions, and stakeholders. This study presents a comprehensive analysis of the opportunities and challenges facing Mongolia in integrating FinTech into its sustainable finance agenda, and SWOT-based strategies. Full article

Due to low susceptibility of coronavirus disease of 2019 (COVID-19) in children, limited studies are available regarding COVID-19 in the pediatric population in Tunisia. The current study evaluated the incidence, clinical characteristics, and outcomes of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection among children hospitalized at Béchir Hamza Children’s Hospital. A retrospective cohort analysis was conducted using the hospital database between March 2020 and February 2022 with children aged ≤15 years with SARS-CoV-2 infection (confirmed by RT-PCR). A total of 327 COVID-19 hospitalized patients with a mean age of 3.3 years were included; the majority were male. Neurological disease (20%) was the most common comorbidity, while fever (95.3%) followed by cough (43.7%) and dyspnea (39.6%) were the most frequent symptoms reported. Severe disease with oxygen requirement occurred in 30% of the patients; 13% were admitted in the Intensive Care Unit. The overall incidence rate of COVID-19 hospitalization (in Tunis governorates) was 77.02 per 100,000 while the inpatient case fatality rate was 5% in the study population. The most prevalent circulating variant during our study period was Delta (48.8%), followed by Omicron (26%). More than 45% of the study population were <6 months and one-fourth (n = 25, 26.5%) had at least one comorbidity. Thus, the study findings highlight the high disease burden of COVID-19 in infants. Full article

The necessity of the typification of the Apocynum L. s.l. (incl. Poacynum Baill. and Trachomitum Woodson) (Apocynaceae) species is crucial for future dogbane diversity estimations. Still, the original material of many taxa of the genus Apocynum s.l. is doubtful or remains to be discovered. This study’s topic is resolving a long-term taxonomic homonymy around the widely used binomial “A. sibiricum”. The misusing of the name “A. sibiricum” became a reason for long-term misunderstanding of the meaning of the binomial Poacynum sarmatiense (Woodson) Mavrodiev, Laktionov & Yu.E.Alexeev (A. sarmatiense (Woodson) Wissjul.; T. sarmatiense Woodson) and therefore for the misestimation of the Apocynum s.l. diversity in Russian and other Eurasian floras. Resolving this issue, here, we designate the lectotype of A. sibiricum Jacq. and the name “A. sibiricum Pall.” was validated within Poacynum as P. pallasianum Mavrodiev, Sytin, Laktionov & Vasjukov nom. nov. (Apocynum sibiricum auct., non Jacq.) with the lectotype selected from the original collections of Peter Simon Pallas. Full article

Insurance pricing is the process of determining the premiums that policyholders pay in exchange for insurance coverage. In order to estimate premiums, actuaries use statistical based methods, assessing various factors such as the probability of certain events occurring (like accidents or damages), where the Generalized Linear Models (GLMs) are the industry standard method. Traditional GLM approaches face limitations due to non-differentiable loss functions and expansive variable spaces, including both main and interaction terms. In this study, we address the challenge of selecting relevant variables for GLMs used in non-life insurance pricing both for frequency or severity analyses, amidst an increasing volume of data and variables. We propose a novel application of the Genetic Algorithm (GA) to efficiently identify pertinent main and interaction effects in GLMs, even in scenarios with a high variable count and diverse loss functions. Our approach uniquely aligns GLM predictions with those of black box machine learning models, enhancing their interpretability and reliability. Using a publicly available non-life motor data set, we demonstrate the GA’s effectiveness by comparing its selected GLM with a Gradient Boosted Machine (GBM) model. The results show a strong consistency between the main and interaction terms identified by GA for the GLM and those revealed in the GBM analysis, highlighting the potential of our method to refine and improve pricing models in the insurance sector. Full article

Background: Janus kinase (JAK) inhibitors represent a novel class of oral therapies showing efficacy in treating ulcerative colitis (UC) and Crohn’s disease (CD), challenging conventional treatment paradigms. Summary: This review provides an overview of the potential novel uses of JAK inhibitors, focusing on their current approved indications and exploring possibilities beyond these indications. Tofacitinib and filgotinib are approved for UC, while upadacitinib is approved for both UC and CD. Additionally, their potential in acute severe UC, as steroid alternatives, and in managing fistulizing CD or extraintestinal manifestations are discussed. Key Message: JAK inhibitors play an important role in IBD (inflammatory bowel disease) treatment; however, clinicians must balance their promising efficacy with safety concerns. Individualized care and vigilance are essential for optimizing therapeutic benefits while mitigating potential adverse effects. Further research is necessary to clarify their efficacy, safety, and potential applications. Full article

This work aimed to improve the oxygen transfer mass coefficient (k_La) in mixing reactors, first evaluating the effect of agitation and aeration and then evaluating the influence of the size and concentration of silica microparticles. Silicon dioxide synthesized via the sol-gel technique, commercial sand, and beach sand were characterized by particle size distribution, scanning electron microscopy, XRD, EDS, FTIR, TG/DTA, and BET. The particles presented average values of approximately 9.2, 76.9, 165.1, and 364.4 µm, with irregular surfaces and different roughness. Silica sol-gel is amorphous while beach and commercial sand have a crystalline structure consisting of silicon, oxygen, and carbon residues. Silica sol-gel presents a higher loss of mass and surface area than other silica microparticles, with a shallow mass loss and a smaller surface. Increasing aeration and agitation improves the k_La, as well as adding silica microparticles. The best k_La was found using silica microparticles with approximately 75 µm concentrations of 1.0 g L⁻¹ (silica sol-gel) and 2.0 g L⁻¹ (commercial and treated beach sand). All silica microparticles used in this work improve mass transfer performance in mixing bioreactors. Full article

Supramolecular hydrogels based on low-molecular-weight compounds are a unique class of so-called “soft” materials, formed by weak non-covalent interactions between precursors at their millimolar concentrations. Due to the variety of structures that can be formed using different low-molecular-weight gelators, they are widely used in various fields of technology and medicine. In this study, we report for the first time an unusual self-assembly process of mixing a hydrosol obtained from L-cysteine and silver nitrate (cysteine–silver sol—CSS) with sodium halides. Modern instrumental techniques such as viscosimetry, UV spectroscopy, dynamic light scattering, zeta potential measurements, SEM and EDS identified that adding fluoride anions to CSS is able to form stable hydrogels of a thixotropic nature, while Cl⁻, Br⁻ and I⁻ lead to precipitation. The self-assembly process proceeds using a narrow concentration range of F⁻. An increase in the fluoride anion content in the system leads to a change in the gel network morphology from elongated structures to spherical ones. This fact is reflected in a decrease in the gel viscosity and a number of gel–sol–gel transition cycles. The mechanism of F⁻’s interaction with hydrosol includes the condensation of anions on the positive surface of the CSS nanoparticles, their binding via electrostatic forces and the formation of a resulting gel carcass. In vitro analysis showed that the hydrogels suppressed human squamous carcinoma cells at a micromolar sample concentration. The obtained soft gels could have potential applications against cutaneous malignancy and as carriers for fluoride anion and other bioactive substance delivery. Full article

With the rapid development of artificial intelligence, computer vision techniques have been successfully applied to concrete defect diagnosis in bridge structural health monitoring. To enhance the accuracy of identifying the location and type of concrete defects (cracks, exposed bars, spalling, efflorescence and voids), this paper proposes improvements to the existing Mask Region Convolution Neural Network (Mask R-CNN). The improvements are as follows: (i) The residual network (ResNet101), the backbone network of Mask R-CNN which has too many convolution layers, is replaced by the lightweight network MobileNetV2. This can solve the problem that the large number of parameters leads to a slow training speed of the model, and improve the ability to extract features of smaller targets. (ii) Embedding attention mechanism modules in Feature Pyramid Networks (FPNs) to better extract the target features. (iii) A path aggregation network (PANet) is added to solve the problem that the model Mask R-CNN lacks the ability to extract shallow layer feature information. To validate the superiority of the proposed improved Mask R-CNN, the multi-class concrete defect image dataset was constructed, and using the K-means clustering algorithm to determine the aspect ratio of the most suitable prior bounding box for the dataset. Following, the identification results of improved Mask-RCNN, original Mask-RCNN and other mainstream deep learning networks on five types of concrete defects (cracks, exposed bars, spalling, efflorescence and voids) in the dataset were compared. Finally, the intelligent identification system for concrete defects has been established by innovatively combining images taken by unmanned aerial vehicles (UAVs) with our improved defect identification model. The reinforced concrete bridge defects images collected by UAVs were used as test set for testing. The result is the improved Mask R-CNN with superior accuracy, and the identification accuracy is higher than the original Mask-RCNN and other deep learning networks. The improved Mask-RCNN can identify the new untrained concrete defects images taken by UAVs, and the identification accuracy can meet the requirements of bridge structural health monitoring. Full article

This work reports the study of metal fragments from Roman pipes excavated from the archaeological site of Pompeii and currently preserved in the deposits of the National Archaeological Museum of Naples (MANN). The Roman pipe, called the tibia, is a reed wind musical instrument similar to the Greek aulos. It can be made of wood, bone, and/or metal. Materials consisting of metal Cu-based alloys were excavated from archaeological burial environments. This research aims to identify the composition of the alloys, characterize the corrosion patinas, and identify any ancient surface treatments on the fragments. Non-invasive and micro-invasive techniques were used to achieve this aim, i.e., optical microscopy, Raman spectroscopy, attenuated total reflectance Fourier-transform infrared spectrophotometry, scanning electron microscopy, and energy dispersive spectrometry. This research contributes to a deeper understanding of the materials and manufacturing techniques used for these instruments, as well as the degradation processes occurring over the centuries. Full article

The pathogenesis of systemic lupus erythematosus (SLE) is linked to the differential roles of toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. TLR7 overexpression or gene duplication, as seen with the Y-linked autoimmune accelerator (Yaa) locus or TLR7 agonist imiquimod, correlates with increased SLE severity, and specific TLR7 polymorphisms and gain-of-function variants are associated with enhanced SLE susceptibility and severity. In addition, the X-chromosome location of TLR7 and its escape from X-chromosome inactivation provide a genetic basis for female predominance in SLE. The absence of TLR8 and TLR9 have been shown to exacerbate the detrimental effects of TLR7, leading to upregulated TLR7 activity and increased disease severity in mouse models of SLE. The regulatory functions of TLR8 and TLR9 have been proposed to involve competition for the endosomal trafficking chaperone UNC93B1. However, recent evidence implies more direct, regulatory functions of TLR9 on TLR7 activity. The association between age-associated B cells (ABCs) and autoantibody production positions these cells as potential targets for treatment in SLE, but the lack of specific markers necessitates further research for precise therapeutic intervention. Therapeutically, targeting TLRs is a promising strategy for SLE treatment, with drugs like hydroxychloroquine already in clinical use. Full article

In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and morphological development in cortical cell culture. Acute buprenorphine treatment had no effect on the excitatory synapse number in astrocyte-free neuron cultures. In conditions where neurons shared culture media with astrocytes, buprenorphine attenuated the synaptogenic capabilities of astrocyte-secreted factors. Neurons cultured from drug-naïve mice showed no change in synapses when treated with factors secreted by astrocytes from POE mice. However, this same treatment was synaptogenic when applied to neurons from POE mice, indicating a complex neuroadaptive response in the event of impaired astrocyte signaling. In addition to promoting morphological and connectivity changes in neurons, POE exerted a strong influence on astrocyte development, disrupting their structural maturation and promoting the accumulation of lipid droplets (LDs), suggestive of a maladaptive stress response in the developing CNS. Full article