Aim: This study aims to analyze the structure of the co-authorship network in viral hepatitis research from 2000 to 2023 using data from the Web of Science (WoS) Core Collection. The objective is to identify key researchers, evaluate the collaborative dynamics, and understand the evolution of scientific contributions in this field. Method: This study utilized network analysis techniques to evaluate 60,720 publications related to viral hepatitis research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: The findings reveal that the viral hepatitis research network is characterized by low network density, indicating sparse overall collaboration. However, the clustering coefficient is high, suggesting strong collaborations within small, cohesive groups. Over the years, researchers such as Stefan Zeuzem, Maria Buti, and Fabien Zoulim have played pivotal roles, serving as central figures in the network. A noticeable increase in network density and clustering from 2020-2023 suggests growing collaboration in recent years.Conclusion: This study underscores the importance of international collaboration in advancing viral hepatitis research. Key researchers have emerged as influential contributors, facilitating global research activities. Network analysis provides valuable insight into the structure of these collaborations and helps identify potential areas for future research and partnerships to combat viral hepatitis globally. The results of this study should be used to reduce global healthcare disparities, promote research collaboration, and address viral hepatitis as a global public health problem.

Aim: This study aims to analyze the collaborative networks and identify key players in autoimmune pancreatitis (AIP) research from 2000 to 2023. Using data from the Web of Science (WoS) Core Collection, I assess the structure and evolution of co-authorship networks to understand collaboration trends and influential researchers in the field.Method: I conducted a network analysis of co-authorship patterns in AIP research using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The analysis included macro-level indicators: network density, clustering coefficient, components, and average distance, as well as micro-level indicators: degree centrality, closeness centrality, and betweenness centrality. These metrics were used to evaluate the connectivity, clustering, and key nodes within the network across three distinct periods: 2000-2009, 2010-2019, and 2020-2023.Result: The analysis revealed that the co-authorship network in AIP research evolved from a fragmented structure with limited collaboration in the early 2000s to a more interconnected but still dispersed network in recent years. Despite an increase in network density and a decrease in the number of disconnected components over time, the overall structure remains highly clustered, with many researchers operating within isolated groups. Key figures, such as Kazuichi Okazaki, Terumi Kamisawa, and Shigeyuki Kawa from Japan, consistently ranked high in centrality measures, highlighting their significant influence and leadership in the field. The findings suggest that while local collaborations are strong, broader international connections are still developing.Conclusion: This study provides a comprehensive overview of the collaborative landscape in AIP research, identifying central researchers and highlighting persistent fragmentation within the network. The prominent role of Japanese researchers in shaping the field underscores the importance of fostering greater international collaboration to bridge gaps between research clusters. Enhancing global partnerships could lead to more integrated and impactful research outcomes, ultimately advancing the understanding and management of autoimmune pancreatitis.

A mass mortality event of Asian seabass Lates calcarifer juveniles occurred in Zhuhai, the main Asian seabass cultured area in mainland China. The fish samples were pooled for pathogen identification and both high viral loads of ISKNV and NNV were detected by real-time microfluidic quantitative PCR. Immunohistochemistry and immunofluorescence showed that strong ISKNV signals were examined in spleen and liver, while strong NNV signals were detected in brain and eye. The multi-tissue homogenates were inoculated into MFF-1 cell and SSN-1 cell, respectively. After several viral passages, both ISKNV and NNV were purely isolated from each other, and designated as ASB-ISKNV-23 and ASB-NNV-23, respectively. The whole genome sequences of ASB-ISKNV-23 and ASB-NNV-23 were determined and annotated. The result showed that ASB-ISKNV-23 and ASB-NNV-23 are composed of 112,236 bp and 4,538 bp, respectively. Phylogeny analysis showed that ASB-ISKNV-23 belongs to ISKNV-II sub-genotype and ASB-NNV-23 belongs to RGNNV genotype. Collectedly, coinfection of ISKNV-II and RGNNV were firstly documented in mass mortality of Asian seabass in mainland China. Importantly, both ISKNV-II and RGNNV were purely isolated using two different permissive cell lines. Our study provides useful information for better understanding the complex pathogenesis regarding the coinfection with ISKNV and NNV in farmed fish.

Off-grid electrification planning increasingly recognizes the importance of productive use of electricity (PUE) to promote community value creation and (financial) project sustainability. To ensure a sustainable and efficient integration in the community and energy system, PUE assets must carefully be evaluated to match both the community needs and the residential electricity demand patterns. We propose a novel methodology interlinking qualitative interviews, statistical analysis, and energy system modelling to optimize decision-making for PUE integration in off-grid energy systems in rural Madagascar by aligning relevant PUE effectively with anticipated residential electricity demand patterns based on socio-economic determinants of the community. We find that a possible contribution of the PUE to reducing the electricity costs depends signifi-cantly on three factors: 1. the residential electricity consumption patterns that are influenced by the socio-economic composition of the community, 2. the degree of flexibility of i) PUE assets and ii) operational preferences of the PUE user, and 3. the capacity of community members to finance and operate PUE assets. Our study demonstrates that significant cost reductions for PUE-integrated off-grid energy systems can be achieved by applying our proposed methodology. When matching PUE and residential consumption patterns, the integration of PUE assets in residential community energy system can reduce the financial risk of operators, provided the PUE enterprise operates reliably and sustainably. We highlight that the consideration of local value chains and co-creation approaches are essential to ensure the energy system is addressing the community’s needs, creates value for the community, enhances the project´s financial sustainability, and is achieving the overall objectives of decentralized energy system planning.

The phenomenon of pathogens co-infection detected in the half fed on humans I. persulcatus tick in the south of the Far East was studied. Researchs were carried out on PEK, Vero, Vero-E6 cell lines, outbred mice, chicken embryos, using ELISA, PCR, IMFA, plaque formation, and electron microscopy. The tick contained an antigen and a genetic marker of the tick-borne encephalitis virus (TBEV). The patient had post-vaccination antibodies in a titer of 1:200, as a result of which, obviously, an antibody-dependent elimination of TBEV occurred. The tick-borne co-isolate also contained an unknown pathogen (Kiparisovo-144 virus), which, in our opinion, was a trigger for the activation of chronic infection in suckling white mice. In the laboratory coisolate, ectromelia virus was present, as evidenced by paw edema during intradermal infection of mice, characteristic rashes on the chorion-allantoic envilope of chicken embryos, and typical plaques on Vero-E6. The Kiparisovo-144 virus was not pathogenic for white mice and chicken embryos, but successfully multiplied in the PEK, Vero, and Vero-E6 lines. Viral co-infection was confirmed by electron microscopy. Passaging on mice contributed to an increase in the virulence of the co-isolate, whose titer increased by 10,000 times by the 5th passage, which poses a serious epidemiological danger.

Abstract: This paper outlines the methodology and results for a two species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA) ) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two species (free-drug and bound-drug) mass transport setup including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of drug between the free and bound-drug states. The model is solved by a 2-D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over our previously developed model using the finite-difference method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 hours (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.

Loyalty is one of the greatest intangible assets that any organization can possess and improving client loyalty is a primary marketing goal that can have a significant financial impact on any business. This quantitative study examined the mediating role of communication on the relationship between satisfaction and loyalty (attitudinal and behavioral) in veterinary clinics, along with the moderating roles of trust, commitment, perceived value, and relational characteristics. Responses collected from 351 pet-owners through social media were analyzed using descriptive and inferential statistics. The results show that attitudinal loyalty (AL) has a strong positive relationship with communication at multiple points in a veterinary clinic whereas the relationship with behavioral loyalty was not as clear. Additional findings suggest that AL, which is influenced by trust in the veterinarian, communication from staff members and commitment, has a strong positive relationship with behavioral intentions, increases the number of products and services that a pet-owner consumes at his or her primary veterinary clinic, and attenuates the role of cost in receiving veterinary care. These findings can help veterinary clinic owners and managers in developing and implementing relationship strategies that improve pet-owner loyalty. The article that follows is a synopsis of the author’s dissertation.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.

: The present paper tackles the important issue of tensile ultimate strength of ceramic matrix composites, using a multiscale approach. The ultimate strength is investigated at the successive increasing length scales inherent to 2D woven SiC/SiC composites, i.e. single filaments, fiber tow, minicomposites reinforced with a single tow, and 2D woven composite. First experimental results on tensile behavior under strain-controlled conditions are summarized for tows, minicomposites and composites. Then, models of tow ultimate failure under controlled force and strain are presented. A criterion of tow failure is developed for filament fracture initiation and then propagation based on applied stress and on filament strength gradient. The model of ultimate failure of minicomposite under strain-controlled condition is based on the strength of filaments in the presence of matrix cracks and the overstress induced by interactions of broken filaments and the matrix. The variability of ultimate strengths of filaments, minicomposites and composites at various gauge lengths is described by linear p-quantile diagrams which indicates that the data follow normal distribution function. The contribution of structural effects to variability of composite and minicomposite strength under strain-controlled loading is analyzed. Their dependence on specimen size is related to reproducibility of critical flaw population and structural effects.

This paper examined the chemoselectivity and diastereoslectivity of silyl nitronate alkenyn-nitroethers in Intramolecular Silyl Nitronate Cycloadditions (ISNC) to produce isoxazole derivatives with interesting medicinal properties. These reactions resulted in the formation of either dihydrofuro[3,4-c]isoxazolines/isoxazolidines and/or alkynyl moieties attached to 2,5-dihydrofuryl carbonyls. It also discerned the diastereoselectivity of the resulting cyclic adducts and compared those to previous findings. The reactions were also investigated with Spartan molecular modeling computations to aide in the understanding of any displayed chemo- and/or stereoselectivity. These [3+2]-cycloaddition reactions demonstrated excellent to complete chemospecificity. The cycloadditions also demonstrated remarkable diastereospecificity in that each diastereomer of the nitroethers resulted in the formation of only one of four possible diastereomeric outcomes. The stereochemistry of the major diastereomers did not agree with previously published findings.

Clinical microbiology studies and systematic reviews have largely concluded that SARS-CoV-2 RNA is rarely present in the urine of COVID-19 patients. Thus, wastewater surveillance has largely focused on human stool and defecation as the relevant matrix and behavior. But, the over-performance of wastewater testing during near-source surveillance, especially in settings where on-site defecation is presumed to be de minimis such as aircraft and non-residential schools, suggests the possibility of SARS-CoV-2 RNA input from a non-fecal source. To revisit the possibility of urine as an explanation, data was compiled from 45 studies reporting on SARS-CoV-2 RNA in the urine of 1,924 COVID-19 patients. In general, the reporting quality was low with most studies (86.7%) failing to report even basic details such as the volume of urine collected. Only 11 reported quantitative data and of these only a single study reported its experiments to the standards established for publication of quantitative PCR data. Taking the data at its face value, the pooled prevalence of urinary SARS-CoV-2 RNA shedding was 11.3% (95%CI: 8.4 - 14.3), which roughly agrees with previous analyses. However, the percentage of variability in the estimate attributable to heterogeneity between studies (I² = 93.66%) warrants careful consideration. Notably, for the 8 studies reporting sufficient workflow information, the observed urinary RNA shedding prevalence was normally distributed (r² = 1.00) as a function of the volume of urine being assayed in a single PCR reaction (i.e., the equivalent sample volume, ESV). The study achieving the highest ESV (83.3 µL of urine) detected SARS-CoV-2 RNA in urine sediments of 95.5% of COVID-19 patients. Conversely, during two studies achieving ESVs of only 2 µL and 11.7 µL of urine, SARS-CoV-2 RNA was not detected in the urine of 72 and 132 patients, respectively. For wastewater surveillance of COVID-19, these observations suggest the rarity of SARS-CoV-2 RNA in urine may be a methodological artifact. Further, the data on which rarity is presumed are of low quality. Beyond COVID-19, the findings demonstrate that clinical studies, by virtue of their design to answer clinically relevant questions, could produce datasets subject to large biases that make them less useful when assessing the feasibility of wastewater surveillance of infectious agents. Wastewater surveillance practitioners must carefully consider the appropriateness and limitations of clinical data considering the important differences between the methods and aims of the two disciplines. Given the great potential of wastewater testing, clinical and environmental microbiologist should collaborate to produce robust quantitative datasets for reliable feasibility assessments for both community and near-source public health surveillance.

Detection and quantification of disease-related biomarkers in wastewater samples, denominated Wastewater Based Surveillance (WBS), has proven a valuable strategy for studying the prevalence of infectious diseases within populations in a time and resource-efficient manner, as wastewater samples are representative of all cases within the catchment area, whether they are clinically reported or not. However, analysis and interpretation of WBS datasets for decision-making during public health emergencies, such as the COVID-19 pandemic, remains an area of opportunity. In this article, a database obtained from wastewater sampling at wastewater treatment plants (WWTPs) and university campuses in Monterrey and Mexico City between 2021 and 2022 was used to train simple clustering and regression-based risk assessment models to allow for informed prevention and control measures in high-affluence facilities, even if working with low-dimensionality datasets and a limited number of observations. When dividing weekly data points based on whether the seven-day average daily new COVID-19 cases were above a certain threshold, the resulting clustering model could differentiate between weeks with surges in clinical reports and periods between them with an 83.3% accuracy rate. Moreover, the clustering model provided satisfactory forecasts one week (79.2% accuracy) and two weeks (72.9%) into the future. However, the prediction of the weekly average of new daily cases was limited (R2 = 0.452, MAPE = 180.2%), likely because of insufficient dimensionality in the database. Overall, while simple, WBS-supported models can provide relevant insights for decision-makers during epidemiological outbreaks, regression algorithms for prediction using low-dimensionality datasets can still be improved.

Background/Objectives: The ongoing COVID-19 pandemic has underscored the need for alternative prophylactic measures, particularly for populations where vaccines may not be effective or accessible. This study aims to evaluate the efficacy of intranasally administered IgY antibodies derived from hen egg yolks as a protective agent against SARS-CoV-2 infection in Syrian golden hamsters, a well-established animal model for COVID-19. Methods: Hens were immunized with the spike protein of SARS-CoV-2 to generate IgY antibodies. These antibodies were extracted from the egg yolks, purified, and their neutralizing activity was tested in vitro. Syrian golden hamsters were then treated with the IgY antibodies before being challenged with SARS-CoV-2. Viral loads were quantified using droplet digital PCR (ddPCR), and lung pathology was assessed through histopathological analysis. Results: The in vitro assays showed that IgY effectively neutralized SARS-CoV-2. In the in vivo hamster model, IgY treatment led to a significant reduction in viral loads and a marked decrease in lung consolidation and inflammation compared to the positive control group. Histopathological findings further supported the protective role of IgY in reducing lung damage caused by SARS-CoV-2. Conclusions: The results demonstrate that IgY antibodies exhibit strong antiviral activity and can significantly reduce SARS-CoV-2 viral loads and associated lung pathology in hamsters. These findings suggest that IgY could be a viable prophylactic option for preventing SARS-CoV-2 infection, particularly for individuals who cannot receive or respond to vaccines. Further studies are warranted to optimize dosage and explore the long-term efficacy of IgY antibodies.

The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

To evaluate new circulating markers related to macrovascular complications (MVC) in type 2 diabetes mellitus (T2DM), we recruited 30 controls (CG), 34 patients with T2DM (DG), and 28 patients with T2DM and vascular complications (DG+C), among them, 22 presented MVC. Pe-ripheral blood was used to determine redox status (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; glucose-6-phosphate dehydrogenase, G6PD) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid pe-roxidation, LPO). Inflammatory markers (IL-1β, IL-6, IL-10, IL-18, MCP-1, TNF-α) and the relative expression of c-miRNAs were analyzed. The real-time PCR results showed that the expressions of miR-155-5p, miR-21-5p, miR-146a-3p, and miR-210-3p were significantly higher in the DG group compared to CG. DG+C group presented statistically relevant differences with CG for four miRs: the increased expression of miR-484-5p, miR-21-5p, and miR-210-3p, and decreased for miR-126a-3p. Moreover, miR-126a-3p was significantly less expressed in DG+C compared to DG. The application of binary logistic regression analysis and construction of receiving operator characteristic curves (ROC) revealed two models with high predictive value for vascular complications presence: 1) HbAc1, creatinine, total cholesterol (TC), LPO, GPx, SOD, miR-126, miR-484. 2) HbAc1, creatinine, TC, IL-6, LPO, miR-126, miR-484. Moreover, our data demonstrated that gender, TC, GPx, CAT, and miR-484 were associated with MVC and exhibited higher predictive values than classical variables. miR-126, miR-484, IL-6, SOD, CAT, and GPx participate in vascular damage development in the studied diabetic population and should be considered for future studies.

Quantifying forest carbon storage to better manage climate change and its effects requires accurate estimation of forest structural parameters such as canopy height. Variables from remote sensing data and machine-learning models are tools that are being increasingly used for this purpose. This study modelled canopy height of forest-savannah mosaics in the Sudano-Guinean zone of Togo. Relative heights were extracted from GEDI and ICESat-2 products, which were combined with optical, radar and topographic variables for canopy height modelling. We tested four methods: Random Forest (RF); Support Vector Machine (SVM); Extreme Gradient Boosting (XGBoost); and Deep Neural Network (DNN). The RF algorithm obtained the best predictions using 98% relative height (RH98). The best performing result was obtained from variables extracted from GEDI data (r = 0.84; RMSE = 4.15 m; MAE = 2.36 m), compared to ICESat-2 (r = 0.65; RMSE = 5.10 m; MAE = 3.80 m). Models that were developed during the study, from the combination of multisource and multisensor data, can be applied over large areas in forest-savannah mosaics, thereby contributing to better monitoring of forest dynamics according to the objectives and requirements of REDD+.

Background: Obesity and Type 2 diabetes (T2D) promote inflammation, increasing the risk of colorectal cancer (CRC). High-fat diet (HFD)-induced obesity plays a key role in these diseases through biological mechanisms. This study examined the effect of genetic background on the multimorbidity of intestinal cancer, T2D, and inflammation due to HFD-induced obesity. Methods: A cohort of 357 Collaborative Cross (CC) mice from 15 lines was fed either a control chow diet (CHD) or HFD for 12 weeks. Body weight was tracked biweekly, and blood glucose was assessed at weeks 6 and 12 via intraperitoneal glucose tolerance tests (IPGTT). At the study's endpoint, intestinal polyps were counted, and cytokine profiles were analyzed to evaluate the inflammatory response. Results: HFD significantly increased blood glucose levels and body weight, with males showing higher susceptibility to T2D and obesity. Genetic variation across CC lines influenced glucose metabolism, body weight, and polyp development. Mice on HFD developed more intestinal polyps, with males showing higher counts than females. Cytokine analysis revealed diet-induced variations in pro-inflammatory markers like IL-6, IL-17A, and TNF-α, differing by genetic background and sex. Conclusions: Host genetics plays a crucial role in susceptibility to HFD-induced obesity, T2D, CRC, and inflammation. Genetic differences across CC lines contributed to variability in disease outcomes, providing insight into the genetic underpinnings of multimorbidity. This study supports gene-mapping efforts to develop personalized prevention and treatment strategies for these diseases.

During the COVID-19 pandemic, wastewater surveillance was used to monitor community transmission of SARS-CoV-2. As new genetic variants emerged, the need for timely identification of these variants in wastewater became an important focus. In response to increased reports of Omicron transmission across the United States, the Oklahoma Wastewater Surveillance team utilized allele-specific RT-qPCR assays to detect and differentiate variants, such as Omicron, from other variants found in wastewater in Oklahoma. The PCR assays showed presence of the Omicron variant in Oklahoma on average two weeks before official reports, which was confirmed through genomic sequencing of selected wastewater samples. Through continued surveillance from November 2021 to January 2022, we also demonstrated the transition from prevalence of the Delta variant to prevalence of the Omicron variant in local communities. We further assessed how this transition correlated with certain demographic factors characterizing each community. Our results highlight RT-qPCR assays as a rapid, simple and cost-effective method for monitoring community spread of SARS-CoV-2 genetic variants in wastewater. Additionally, they demonstrate that specific demographic factors such as ethnic composition and household income can correlate with the timing of SARS-CoV-2 variant introduction and spread.

Damage to peripheral arteries by the atherosclerotic process accounts for about 3% of the world's population, which puts this problem in the category of major social problems. Modified lipoproteins and cholesterol crystals are known to accumulate in the arterial intima and cause the formation of proatherogenic macrophages, foam cells, and inflammation. Defective efferocytosis of apoptotic foam cells leads to the formation of a necrotic core, a sign of failure to resolve inflammation. Resolution of inflammation is mediated by specialized pro-resorption lipid mediators, proteins and signaling gases. Improving the balance between pro-inflammatory and anti-inflammatory factors contributes to the reverse development of local atherogenesis. Active direct intervention in the reconstruction of the adventitial layer of the arterial wall using cholesterol-affinity polysaccharide hydrogels containing a cocktail of growth factors creates conditions for the formation of additional extracellular matrix and reversal of cholesterol mass from the subintimal zone. Creating concentration and electrostatic gradients in the adventitia zone using a hydrogel may be one of the effective ways to degrade early soft atherogenic plaques and locally restore the damaged structure of the vessel wall. Growing scientific interest in the previously insufficiently studied adventitia indicates its important role in angionesis and atherogenesis.

Wastewater genomic surveillance is an efficient and economic approach to track infectious diseases and can help detect unusual epidemiological events. The current study uses this approach for the first time in Morocco to monitor the epidemiology of SARS-CoV-2 and Influenza A, B and RSV virus infections during the third wave of COVID-19 caused by the Omicron variant. The virome was concentrated from wastewater collected from two sewer sheds of two cities, Agadir and Inezgane, using the PEG/NaCl method. The viral copy number was determined using qRT-PCR. All 26 samples in both cities were tested positive for SARS-CoV-2 at various viral loads. For Influenza A virus, two samples were tested positive in Inezgane. The estimated SARS-CoV-2 viral RNA copy numbers observed were then used to estimate the number of infected individuals using the SEIR model. The number of viral copies of SARS-CoV-2 for Agadir and Inezgane varied from 82932 ± 15479 to 507865 ± 58759 copies/L and 61244 ± 8552 to 497506 ± 18061 copies/L, respectively. The estimated number of cases correlates positively with the number of reported cases. Next Generation Sequencing showed that samples contain the following two variants: BA.1 and BA.2 that have been detected in clinical samples. This study demonstrates the effectiveness and feasibility of wastewater genomic surveillance in monitoring pathogens such as SARS-CoV-2 in Morocco.

This study evaluated the epidemiological and genetic susceptibility profile caused by coronavirus 2 (SARS-CoV-2) in children ≤3 years of age with acute gastroenteritis (AGE) or acute respiratory infection (ARI), living in the northwestern region of the Amazon (NWAR). Fecal and saliva sam-ples collected from 202 children (n=404) were subjected to detection of SARS-CoV-2 by RT-qPCR. Polymorphisms in the angiotensin-converting enzyme (ACE rs4646994) and ACE2 G8780A; rs2285666) genes were detected by SYBR GREEN real-time PCR and PCR/Alul digestion, respec-tively. Secretory and Lewis status of histo-blood group antigen (HBGA) was performed using phenotyping/ELISA. Frequencies for the AGE group: SARS-CoV-2; 8.9%; ARI group: SARS-CoV-2; 2.9%. The ACE I/I homozygous polymorphism gene was majority. Males with the ACE2 G8780A SNP were more susceptible to ARI symptoms than AGE (OR = 3.85; 95% CI-1.42-10.38; P 0.007). Most children were secretory FUT2 phenotype (92.6%). Surveillance of diarrhea and respiratory infections in children, along with understanding their causes, are crucial for identifying preven-tion and control strategies and for prioritizing and developing new vaccines. Clinical manifesta-tions of COVID-19 in children ≤3 years of age include AGE.

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants is a challenge to public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4,213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 from California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage, or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages.

With the aim to produce new heterocycle molecules, the previously reported 2-(aminomethyl)-2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one was converted efficiently by reacting with N,N’-dithiocarbonyldiimidazole (DTCI), to produce the substituted imidazolidine-2-thione moiety inserted in a three fused ring scaffold of the title compound. The molecular composition was confirmed by a high-resolution MS experiment, and its structure was elucidated by 1H, 13CNMR, and IR analyses. The thioacetamide form of the product was supported by density functional theory (DFT)-NMR analysis where 13C chemical shifts of thioacetamide form and of its iminothiol tautomer were calculated in chloroform at the BP86 /Jgauss-TZP2 level of theory. The very good linear correlation between 13C chemical shifts by experiment and by calculation for the NHC=S form confirmed the structure.

Recent advancements in communication technology have catalyzed the widespread adoption of realistic content, with augmented reality (AR) emerging as a pivotal tool for seamlessly inte-grating virtual elements into real-world environments. In construction, architecture, and urban design, the integration of mixed reality (MR) technology enables rapid interior spatial mapping, providing clients with immersive experiences to envision their desires. The rapid advancement of MR devices, or devices that integrate MR capabilities, offers users numerous opportunities for enhanced entertainment experiences. However, to support designers at a high level of expertise, it is crucial to ensure the accuracy and reliability of the data provided by these devices. This study explores the potential of utilizing spatial mapping within various methodologies for surveying architectural interiors. The objective is to identify optimized spatial mapping procedures and determine the most effective applications for their use. Experiments were conducted to evaluate the interior survey performance, using HoloLens 2, iPhone 13 Pro for spatial mapping, and photogrammetry. The findings indicate that HoloLens 2 is most well-suited for the tasks exam-ined in the scope of experiments. Nonetheless, based on the acquired parameters, the author also proposes approaches to apply the other technologies in specific real-world scenarios.

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants has evolved and some of them have shown higher transmissibility becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points including the early stages of the pandemic are very crucial for understanding the evolution and transmission patterns. Using whole genome sequences, our study describes the early landscape of SARS-CoV-2 variants in central India retrospectively (including the first known occurrence of SARS-CoV-2 in Madhya Pradesh). We performed amplicon based whole genome sequencing of randomly selected SARS-CoV-2 isolates (n=38) collected between 2020-2022 at state level VRDL, ICMR-NIRTH, Jabalpur from 11899 RT-qPCR positive samples. We observed the presence of five lineages namely B.1, B.1.1, B.1.36.8, B.1.195 and B.6 in 19 genomes from the first wave cases and variants of concern (VOC) lineages i.e. B.1.617.2 (Delta), and BA.2.10 (Omicron) in the second wave cases. There was a shift in mutational pattern of SRAS-CoV-2 strains from the second wave in contrast to the first wave. We have identified five immune escape variants in the S gene: P681R, P681H, L452R, Q57H, and N501Y in the isolates collected during the second wave. Furthermore, these genomes were compared with 2160 complete genome sequences reported from central India that encompass 109 different SARS-CoV-2 lineages. Among them, VOC lineages Delta (28.93%), and Omicron (56.11%) were circulating predominantly in this region. This study provides useful insights into the genetic diversity of SARS-CoV-2 strains over the initial course of the COVID-19 pandemic in central India.

Predicting type 2 diabetes mellitus (T2DM) using phenotypic data with machine learning (ML) techniques has received significant attention in recent years. PyCaret, an ML tool that enables the simultaneous application of 16 different algorithms, was used to predict T2DM using phenotypic variables from the “Nurses’ Health Study” and “Health Professionals’ Follow-up Study” datasets. Ridge classifier, Linear Discriminant Analysis, and Logistic Regression (LR) were the best-performing models for the male-only data subset. For the female-only data subset, LR, Gra-dient Boosting Classifier, and CatBoost Classifier were the strongest models. The AUC, accuracy, and precision were 0.77, 0.70, and 0.70 for males and 0.79, 0.70, and 0.71 for females, respective-ly. The feature importance plot showed that familial history of diabetes (famdb), never having smoked, and high blood pressure (hbp) were the most influential features in females, while famdb, hbp, and current smoking were the major variables in males. In conclusion, PyCaret was used successfully for speed analysis for the prediction of T2DM by simplifying complex ML tasks. Gen-der differences are an important consideration for T2DM prediction. Despite this comprehensive ML tool, phenotypic variables alone may not be sufficient for early T2DM prediction; genotypic variables could also be used in combination for future studies.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

Epigallocatechin gallate (EGCG), the principal catechin in green tea, exhibits diverse therapeutic properties. However, its clinical efficacy is hindered by poor stability and low bioavailability. This study investigated solid particle-in-oil-in-water (S/O/W) emulsions stabilized by whey protein isolate (WPI) and sodium caseinate (NaCas) as carriers to enhance the bioavailability and intestinal absorption of EGCG. Molecular docking revealed binding interactions between EGCG and these macromolecules. The emulsions exhibited high encapsulation efficiencies and augmented EGCG bioaccessibility by 64% compared to free EGCG in a simulated gastrointestinal digestion model. EGCG-loaded emulsions demonstrated minimal cytotoxicity towards Caco-2 cells and facilitated EGCG transport across the intestinal epithelial layer without compromising tight junction integrity. Notably, EGCG-loaded emulsions protected Caco-2 cells against oxidative stress by suppressing intracellular reactive oxygen species generation. The results demonstrate the potential of WPI- and NaCas-stabilized S/O/W emulsions to enhance the bioavailability, intestinal absorption, and bioactivity of EGCG, expanding its applications in functional foods and nutraceuticals.

The study conducts a comparative analysis of solar radiation estimation methods, assessing the efficacy of the Heliosat-2 algorithm against ground measurements across seven distinct countries: Netherlands, Spain, Japan, Namibia, South Africa, Saudi Arabia, and India. To achieve this, it utilizes two distinct satellite data sources—Himawari-8 for Japan and Metosat Second Generation-MSG for the rest of the countries—spanning the years Jan 2022 to April 2024. A robust methodology for determining albedo parameters specific to Heliosat-2 was developed. During cloudy days, the estimates provided by Heliosat-2 generally exceeded the ground measurements in all the countries. Conversely, on clear days, there was a tendency for underestimation, as indicated by the median value of the mean bias (MB) across most of the countries. The Heliosat-2 model slightly underestimates daily radiation values, with a median MB ranging from −27.5 to +10.2 W.m⁻². Notably, the median root mean squared error (RMSE) on clear days is significantly lower, with values ranging from 24.8 to 108.7 W.m⁻², compared to cloudy days where RMSE values lie between 75.3 and 180.2 W.m⁻². In terms of R² values, both satellites show a strong correlation between the estimated and actual values, with a median value consistently above 0.86 on a monthly scale and over 92% of daily data points falling within ±2 standard deviation.

A two-qubit Hamiltonian model exhibiting an SU(2) symmetry is considered. The related dynamical problem results to be then exactly solvable both in the time-independent and in the time-dependent case. Basing on the formal, general form of the related time evolution operator, the time-dependence of the level of entanglement of some initial conditions is studied within both the Rabi and the Landau-Majorana-Stückelber-Zener scenarios.

Metabolic syndrome (MS), a complex pathology with features like abnormal body fat distribution, insulin resistance, and dyslipidaemia, contributes to higher cardiovascular (CV) risk. A cross-sectional study including 87 individuals, assessed CV risk in elderly patients with type 2 diabetes and MS in Algarve, Portugal. The 10-year CV risk was estimated using the ADVANCE risk score calculator. The reductions in CV risk were estimated by adjusting the data inputted on the online tool to achieve systolic blood pressure (SBP) <130 or <120 mmHg, and LDL-cholesterol <70 mg/dL. Beyond waist circumference, the mean number of clinical features of MS was 3.14±0.84, without significant sex differences. The mean CV risk was 22.5% (CI: 20.3-24.7). Sex-specific analysis showed higher risk in males (24.2%, CI: 21.3-27.0) vs. females (19.7%, CI: 16.2-23.3; p=0.028). Hypothetical risk reductions show that lowering SBP to <130 mmHg could significantly lower the risk by an average of 9.2% (CI: 7.7-10.7), whereas 34.5% of the participants would be out of the diagnostic criteria for MS. When comparing each potential intervention with current risk, all interventions significantly reduce the 10-years CV risk. The study highlights the potential of blood pressure control in reducing CV risk and the importance of multifaceted risk reduction strategies.

Background and Objectives: To investigate the relationship between the SII index and the micro-macro complications and death that develop in the first year and the following 3 years, following the calculation of the index in type 2 diabetic retinopathy patients. Materials and Methods: This study was performed retrospectively with 523 type 2 diabetic retinopathy patients admitted to the endocrinology outpatient clinic of our hospital between January 2019 and December 2019. The demographic, and clinical characteristics of the patients were evaluated using descriptive statistics. Shapiro-Wilk test was used for the normal distribution of quantitative data; Mann-Whitney U, Mc Nemar Chi-square, and Cochran's Q tests were used to analyze SII values between groups and complication rates by years; sensitivity and specificity were determined by ROC analysis and considered statistically significant with a significance level of P

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

Reservoirs created by damming rivers significantly modify the environment and problems may arise: the storage of nutrients and organic matter in reservoirs often leads to decreased water quality due to eutrophication. Reservoirs built on lowland rivers are exposed to significant nutrient loads, often leading to eutrophication. In this article, the Sulejów Reservoir, in Central Poland, was the subject of the research, which focused on the use of Sentinel-2 remote sensing data to detect phytoplankton blooms, and on understanding the pattern of wind-driven surface currents using the CCHE2D model (a depth-averaged hydrodynamic model). The calculation of the total phosphorus load has shown that the reservoir mainly acts as nutrient storage. Still, during the low flow and intensive phytoplankton bloom, it can be a source of nutrients. The distribution of phytoplankton bloom on the Sulejów Reservoir was documented using eight Sentinel-2 satellite images from the vegetation season of 2020 and the Normalized Difference Chlorophyll Index (NDCl). Coupling remote sensing data and numerical modelling helps to interpret the hydrodynamic model results and understand nutrients and sediment dynamics within the reservoir. Hydrodynamic modelling combined with remote sensing data can be a valuable tool for selecting appropriate locations for water quality measurements at monitoring stations.

Objective: The aim of our study was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Results: There was a statistically significant age difference between the two study periods, both by the average age of patients and by age group. The mean difference was 32 years before the pan-demic and 35 years during the pandemic (p-value >0.05). The majority of patients presenting for investigations before and during the pandemic were in the 30-39-year-old age group (31.95%, respectively; 34.2% (p-value = 0.003). The biggest patient loss ratio identified by age group was in the 50–59 years: 14,53% in the pre-pandemic period and 9,1% in the pandemic period. In the pan-demic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the prepandemic period, with an increase in more severe lesions in the pandemic period, has a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusion: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group 50–59 years and a decrease in patients with rural residence. In our study, we found an increase in cervicorrhagia as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

The proliferation of SARS-COV-2 through enhanced viral replication and its subsequent triggering of cytokine storm, are some of the hallmark phenotypes in severe COVID-19 patient cases. Cyclosporine, an immunosuppressant drug and Selinexor, an inhibitor of nuclear transporter protein, both have been successfully demonstrated to be effective against SARS-COV-2 infection by targeting those functions individually. However, the highly multifactorial pathology of SARS-COV-2 infection hinders any mono-therapeutic strategy to become an optimal option. In this study, we assess the potential efficacy of the Cyclosporine-Selinexor combination on an integrated interactome by adopting a network-medicine-based repositioning technique, where disease proximity, functional proximity and their topological separation are evaluated, followed by a robust statistical significance test. Results have shown that both drug target modules are highly proximal to the SARS-COV-2 disease modules in terms of network topology and functional associations, in a statistically significant manner, individually. Functional enrichment of both drug modules and SARS-COV-2 infected modules has shown that two drugs target the functions related to viral replication and cytokine storm during infection. Moreover, a high degree of network separation been those two drug target modules has been observed, revealing ``complementary exposure`` patterns, rendering this drug combination as an effective one against SARS-COV-2 infection. We hope that our results will encourage researchers to further investigate the potency of Cyclosporine and Selinexor combination in vivo or in vitro, and ultimately lead that up to clinical trials to treat SARS-COV-2 patients.

Keywords: COVID-19, SARS-CoV-2, Antibody, ELISA, Spike, S1, S2, RBD, epitopes, Neutralization

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer became the leading cause of death in several countries. Our objective was the determination of whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study is a nationwide analysis performed in Hungary. Study population was divided into a group with type 2 diabetes mellitus and into a non-diabetic group. The primary outcome was the risk related to overall cancer incidence. A key secondary outcome was the overall incidence of cancer in distinct study years. Further outcomes were the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, P&lt;0.0001) in patients with diabetes as related to controls. The odds ratio was higher in males than in females. The highest risk was found in the 18-39-year-old subgroup. The annual cancer incidence rate declined in controls, but not in patients with diabetes. Several types of cancer showed a decreasing tendency in non-diabetic controls.; (4) Conclusions: type 2 diabetes is associated with a higher risk of cancer. High risk in young patients with type 2 diabetes suggests that these young individuals should be considered as a risk group.

The aim of this study was to determine the microbial stability, challenge to L. monocytogenes, and some physicochemical properties of turkey breast meat by alginate-based coating enriched with postbiotics (8% concentration, CFS) of Bifidobacterium bifidum DSM 20456 and Bifidobacterium bifidum BB12 strains. For this purpose, firstly, some antimicrobial and total phenolic matter, flavonoid, and DPPH activity values of postbiotics were determined. In addition, FTIR analysis was performed to see the intermolecular interactions of the biological coating agent. As a result of the study, alginate solution with postbiotic showed significant differences in pH, a*, b*, yeast-mold values of turkey meat during storage (7 days), while L* value, total aerobic mesophilic bacteria count (TMAP), psychrotrophic bacteria (PAB), lactic acid bacteria (LAB) and Listeria monocytogenes count were not effective (p&gt;0.05).

Before December 2020, Antarctica had remained free of Covid-19 cases. The main concern during the pandemic was the limited health facilities available at Antarctic stations to deal with the disease, as well as the potential impact of SARS-CoV-2 on Antarctic wildlife through reverse zoonosis. In December 2020, 60 cases emerged in Chilean Antarctic stations, disrupting the summer campaign with ongoing isolation needs. The SARS-CoV-2 RNA was detected in the wastewater of several scientific stations. In Antarctica, treated wastewater is discharged directly into the seawater. No studies currently address recovery of infectious virus particles from treated wastewater, but their presence raises the risk of infecting wildlife and initiating new replication cycles. This study highlights the initial virus detection in wastewater from Antarctic stations, identifying viral RNA via RT-qPCR targeting various genomic regions. The virus's RNA was found in effluent from two wastewater plants at Maxwell Bay and O’Higgins Station on King George Island and the Antarctic Peninsula, respectively. This study explores the potential for reverse zoonotic transmission of SARS-CoV-2 from humans to Antarctic wildlife due to the direct release of viral particles into seawater. The implications of such transmission underscore the need for continued vigilance and research.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

(1) Background: The aim of study was to investigate the salt consumption by children and adolescents from the Silesian Province (Poland), taking into account the region’s dietary traditions and number of years of school education. (2) Methods : 300 students aged 10–18 from different types of schools, were enrolled in the study and divided into groups in terms of: school, sex, the state of nutrition. The survey questionnaire about dietary habits, including the frequency and serving size with respect to 12 salty products was used. On the basis of the frequency and the amount of consumed products, as well as the data on salt content, the amount of total daily intake of salt was estimated.; (3) Results: The mean daily intake of salt by children and adolescents was 1.083 g ( 0.433 g of sodium); children aged 10–12 consumed the highest amount of salt (1.296 g/day) compared to pupils aged 13–15 (1.131 g of sodium) and adolescents aged 16–18 (0.863 g/day); (4) Conclusions: With age, as a result of various factors, the consumption of salt declines. The parents impact and the familial socio-environmental factors begin to wane, and other factors start to have influence, e.g. school education of healthy lifestyle, health behavior of peers.

Abstract Background: Metabolic syndrome (MetS) is a complex disorder characterized by insulin resistance (IR), central obesity, atherogenic dyslipidemia and higher glucose levels. It increases the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), imposing an economic burden on the healthcare system. However, the historical origins of MetS as well as the development and evolution of its definitions have not been conclusively documented in the literature. Aim: This study seeks to enhance the understanding of the developmental trends of MetS during the preceding two decades, placing particular emphasis on the definition, diagnosis and prevalence. Methods: An extensive search was performed from 1920 to 2023 across prominent scientific research engines, including Scopus, PubMed, MDPI, and others. Results: Despite advancements, many aspects of MetS remain inadequately understood. As the understanding of the nature and pathophysiology of MetS progresses, the development and refinement of its diagnostic criteria, and assessment and treatment guidelines will continue. Additionally, there exists significant variation in the global prevalence of metabolic syndrome, ranging from 14 to 39%. This prevalence is projected to increase due to the adoption of less healthy dietary patterns and sedentary lifestyles. The observed disparities in metabolic syndrome prevalence can be attributed to multiple factors, including demographic characteristics. Furthermore, the lack of a standardized definition across studies also contributes to the variation in reported prevalence rates. Conclusion: Further studies focusing on the standardization of the MetS definition across different research are crucial. The establishment of consistent criteria would enhance the reliability and validity of research findings, enabling more meaningful comparisons and interpretations.

The APIS Breast Cancer Subtyping Kit is an mRNA-based assessment of the three biomarkers routinely assessed in all newly diagnosed breast cancers (BC), estrogen receptor (ER), progesterone receptor (PR), and HER2 as well as an additional four genes that create a novel proliferation signature, MKI67, PCNA, CCNA2, KIF23. Taken together the data is used to produce a molecular sub-type for every sample. The kit was evaluated against the current standard protocol of immunohistochemistry (IHC) and/or in situ hybridization (ISH) in breast cancer patients. The data was presented at the weekly breast Multidisciplinary Team (MDT) meeting. 98 consecutive cases of pre-operative breast cancer core biopsies and two core biopsy of nodal metastases yielding 100 cases were assessed. IHC and APIS Results were available for 100 and 99 cases. ER was concordant in 97% cases, PR in 89% and HER2 results were concordant with IHC/ISH in 100% of the cases. Ki-67 IHC was discordant in 3% cases when compared with MK167 alone but discordant in 24% when compared with the four gene proliferation signature. In conclusion, our study, indicates that the APIS Breast Cancer Subtyping Kit is highly concordant when compared to the results produced for ER/PR/HER2 by IHC and/or ISH. The assay could play a role in the routine assessment of newly diagnoses Breast Cancer (BC) specimens.

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of an ongoing, open-label, phase 2/3 study of monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy, participants ≥12 years old (N=412 [12‒17 years, N=30; 18‒55 years, N=174; >55 years, N=208]) who previously received ≥3 doses of a US-authorized mRNA vaccine, the most recent being an Omicron BA.4/BA.5-adapted bivalent vaccine ≥150 days before study vaccination, were vaccinated. Serum 50% neutralizing titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 were measured 7 days and 1 month after vaccination in a subset of ≥18-year-olds (N=40) who were positive for SARS-CoV-2 at baseline. Seven-day immunogenicity was also evaluated in a matched group who received bivalent BA.4/BA.5-adapted BNT162b2 in a previous study (NCT05472038). There were no new safety signals; local reactions and systemic events were mostly mild to moderate in severity, adverse events were infrequent, and none led to study withdrawal. The XBB.1.5-adapted BNT162b2 induced numerically higher titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 than BA.4/BA.5-adapted BNT162b2 at 7 days and robust neutralizing responses to all 3 sublineages at 1 month. These data support a favorable benefit-risk profile of XBB.1.5-adapted BNT162b2 30 μg. NCT05997290

Keywords: Spine surgery 1; Metastatic spinal cord compression 2; Spinal metastasis 3; Cancer treatment.

The emergence of SARS-CoV-2 subvariant BA.2.86, also known as Pirola, has raised concerns about its transmissibility, virulence, and immune escape. The aim of this letter is to address the current evidence on the origin, spread, and characteristics of Pirola, and discuss its implications for public health and vaccine development. The need for enhanced surveillance, genomic sequencing, and epidemiological studies to monitor the evolution and impact of Pirola and other SARS-CoV-2 variants are highlighted in this letter along with the importance of global cooperation and coordination to prevent and control future outbreaks of this novel coronavirus strain.

During the last decades, a growing number of studies have shown that infections during pregnancy have an important impact on both pregnant women and their fetuses. Our goal was to identify newborns from pregnancies with SARS-CoV-2 infection and to investigate the extension of neonatal complications using cardiac, abdominal and cerebral ultrasonography, hearing testing and indirect ophthalmoscopy. By contrast, neonates whose mothers were vaccinated against COVID-19 during pregnancy and those from pathology-free pregnancies have been examined. A total of 458 newborns were included, over a period of 10 months, divided into 3 groups, COVID-19 group, vaccine group and control group. Although 6 cardiac malformations were found in the COVID-19 group, no correlation was made compared to the vaccine and control group (p=0.07). Grade 1 intraventricular hemorrhage and hypoxic ischemic encephalopathy were the most prevalent among neonates from mothers with SARS-CoV-2 infection (p=0.002 and p&lt;0.001, respectively). The kidney anomaly found to be most frequent in this group was grade 1 unilateral hydronephrosis (p&lt;0.001). COVID-19 disease during the gestational period had no effect on the auditory or visual function. Despite the fact that our observations are relevant, further studies investigating the effects of SARS-CoV-2 infection during pregnancy and the neonatal outcomes are necessary.

Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection, however no clinical trial data are available and combined use of direct acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. To assess the cooperative effects of dual drug combinations in vitro, we used a VERO E6 cell based in vitro system with the ancestral B.1 or the highly divergent BQ.1.1 virus to test pairwise combinations of the licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) and the active metabolite of molnupiravir (EIDD-1931) as well the combination of RDV with four licensed mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested only with the susceptible B.1 virus). According to SynergyFinder 3.0 summary and weighted scores, all the combinations had an additive effect. Within DAA/DAA combinations, paired scores with the B.1 and BQ.1.1 variants were comparable. In the post-hoc analysis weighting synergy by concentrations, several cases of highly synergistic scores were detected at specific drug concentrations, both for DAA/DAA and for RDV/mAb combinations. This was supported by in vitro confirmation experiments showing a more than linear shift of a drug effective concentration (IC50) at increasing concentrations of the companion drug, although the effect was prominent with DAA/DAA combinations but minimal or null with RDV/mAb combinations. These results support a cooperative effects of dual drug combinations in vitro, which should be further investigated in animal models before introduction into the clinic.

Results showed that mulberry leaves could significantly reduce backfat thickness (P&lt;0.05) and increase intramuscular fat (IMF) content (P&lt;0.05). Lipidomics analysis showed that mulberry leaves improved lipid profile composition and increased the proportion of triglycerides (TG). Interestingly, IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG−005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, Limosilactobacillus, and so on. At the same time improve the L-tyrosine-baton rouge ester, Oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, Mulberrin relative abundance. In this study, we found that mulberry leaves could extremely significantly increasing the mRNA relative expression of lipoprotein lipase (LPL), fatty acid-binding protein 4 (FABP4) and peroxisome proliferators-activated receptor γ (PPARγ) in muscle (P＜0.01), significantly increasing mRNA relative expression of diacylglycerol acyltransferase 1 (DGAT1) (P＜0.05) and significantly decreasing the mRNA relative expression of acetyl CoA carboxylase (ACC) (P＜0.05), and aignificantly upregulated hormone-sensitive triglyceride lipase (HSL), peroxisome proliferators-activated receptor α (PPARα) mRNA relative expression (P＜0.05) in backfat. In addition mulberry leaves could increased serum leptin and adiponectin (P＜0.01). Ultimately lead to up-regulation of IMF and down-regulation of backfat.

The COVID-19 pandemic has created unique challenges for people with comorbidities, including hereditary diseases and cancer cancers. Several studies have reported a link between the presence of disease-causing genetic variants and the outcome of the COVID-19 infection. In this study, we used clinical exome sequencing in a cohort of 840 COVID-19 patients to identify pathogenic and likely pathogenic genetic variants present in these individuals. While we did not identify any statistically significant differences in the overall burden of pathogenic variants between different patient groups, we discovered three known pathogenic alleles associated with hereditary cancer syndromes, including a frameshift mutation in MSH6 and two missense mutations in TP53. The patients carrying these mutations presented with different severity of the disease and outcome. Thus, a 58-year old male subject with an MSH6 mutation developed a severe form of COVID-19 that resulted in death, even though the patient had few pre-existing conditions and no evidence of malignant tumors. On the other hand, two female subjects carrying pathogenic TP53 variants successfully recovered from the disease despite suffering from various forms of cancer. Our results highlight the importance of personalized approaches to the diagnosis, management and treatment of COVID-19 in patients with specific genetic mutations. Further studies are needed to elucidate the complex relationship between these mutations and COVID-19.

Influenza is well-known to have a considerable influence on healthcare system, therefore, vaccination plays a significant role in dealing with severe consequences. Close attention is paid to the development of tetravalent adjuvanted vaccines, containing antigens of two influenza A subtypes (H1N1, H3N2) and two influenza B subtypes (Victoria, Yamagata) to increase the effectiveness of influenza prevention. In this work we present the results of pre-clinical study of innovative subunit tetravalent candidate influenza vaccine, with addition of betulin as adjuvant, TetraFluBet. The study was conducted using female BALB/c mice, male and female mongrel rats and guinea pigs. TetraFluBet and commercially available vaccines were injected intraperitoneally twice in a 14-day interval after intranasal infection with 5LD50 and 10LD50. Chronic toxicity was assessed by immunohistochemistry of extracted organs and by hematological and biochemical blood parameters. Protectivity and immunogenicity were evaluated using hemagglutination inhibition and microneutralization with MDCK assays. Chronic toxicity study did not reveal any side effects of candidate TetraFluBet vaccine on both rats and guinea pigs. One vaccination dose of TetraFluBet provided 100% protectivity against all 4 influenza subtypes and significantly increased neutralizing antibody activity in response to immunization of influenza subtypes. Pre-clinical candidate vaccine TetraFluBet confirmed its safety along with specific activity, showed high immunogenicity and can be recommended for further clinical studies.

Among the number of hurdles that the vaccines based in modRNA platforms have been facing, there is now another critical one: immune imprinting which decreases even more the effectiveness of the modRNA Covid vaccines.

Tocilizumab against interleukin-6 receptor (IL-6R) has been demonstrated to inhibit the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of Tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels re-mains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as our human CRC xenograft models with anti-IL-6R antibody (Tocilizumab) therapy. IL-6R expression levels, the histology of CRC growth/ invasiveness and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels exerted better responsiveness in Tocilizumab therapy than the treated HT-29 group. Likewise, therapeutic effects of Tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, the invasiveness with MMP-9 proteinase expressions, ERK 1/2 and STAT3 signaling transduction in SW480 treatment group were superior to HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of Tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, Tocilizumab may serve as a targeted and promising anti-CRC therapy.

Cross-sectional survey was conducted to capture the true extent of COVID-19 exposure among students and staff of Polytechnic High School (PHS). Random cluster sampling was carried out between May 19 and August 18, 2022, after the fourth wave of COVID-19 transmission. IgM and IgG SARS-CoV-2 antibodies were screened using WANTAI SARS-CoV-2 ELISA assays. Seroprevalence and descriptive statistics were calculated. Moreo-ver, the association between seropositivity and different factors (age, gender, preventive measures comorbidity, and symptoms, etc.) was determined using Logistic Regression. The overall IgG and IgM seroprevalence were 92% and 6.91% respectively. We found a higher IgM seroprevalence in men than women (9.4% vs. 5.6%) and a lower IgM seroprevalence in (18-25) age group compared to (55-65) years. Low compliance with preventive measures was found with a significant IgM seroprevalence depending on non-respect of social distancing (p = 0.008). A total of 70% of participants presented symptoms linked to COVID-19 at the moment of the survey. Results revealed a significant difference according to IgG seroprevalence among participants who declared fa-tigue symptoms 92.06% compared to those who did not 80.39% (p = 0.0027). IgM seropositivity was associated with Body Mass Indice (BMI) categorized (O.R. 0.238, p = 0.043), ethnic group (O.R. 0.723, p = 0.046) and marital status (O.R. 2.399, p = 0.021). Moreover, IgG seropositivity was associated with Chronic sinusitis comorbidity (O.R. 0.238, p = 0.043) and vaccination status (O.R. 4.741, p < 0.001). The majority of students and staff have al-ready been exposed to SARS-CoV-2 and confirm the circulation of SARS-CoV-2 in PHS at the time of the survey. Our results underline the importance of sero-epidemiological surveys to estimate the real impact of the COVID-19 pandemic in a community and to monitor disparities in antibody response in the population.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, of cellular glucose uptake, of lipolysis, and of thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to lack of clinically relevant changes of body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "break-through infections" have been documented in patients with complete primary vaccination course. Most of the SARS-CoV-2 neutralizing antibodies pro-duced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of the host. The aim of this study is to compare the titers of neutralizing an-tibodies against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). 293 HCWs were enrolled and divided into three cohorts as follows: 91 recovered from SARS-CoV-2 infection (nVP); 102 vac-cinated who became positive after the primary cycle (VP); 100 vaccinated with complete primary cycle who concluded the follow-up pe-riod without becoming positive (VN). Higher neutraliza-tion titers were observed in the vaccinated subjects’ arms com-pared to the nVP arm. Differences in neutralization titers between arms for single variant were statistically significant (p<0.001) except for titers against the Alpha variant (p<0.05) between nVP and VP. Within the nVP group, the number of subjects with the absence of neutralizing antibodies was high. The presence of high-er titers in patients with a complete primary cycle compared to patients recovered from the infec-tion suggests a better efficacy of artificial immunization compared to natural im-munization, further encouraging the promotion of vaccination even in subjects with previous infection.

Introduction: Post-COVID-19 syndrome (PCS) is a multisystemic disorder marked by impaired physical performance as one lead symptom. Since it has been suggested that endurance training as part of medical rehabilitation may be effective to improve physical performance capacity in PCS, this study aimed to compare different modes of aerobic endurance training. Methods: Hundred-ten PCS patients (49.3±11.8 years, 38% women, time after infection=260.2±127.5 days) underwent detailed clinical screening including symptom-limited cardiopulmonary exercise testing at admission and after 4-6 weeks of inpatient medical rehabilitation. Questionnaires were used to assess disease perception. Patients performed controlled isocaloric cycle ergometer training (3-5 sessions/week, 18 min) as either continuous training (CT) at 50% of maximal workload or as interval training (IT, load=60%, relief=30%). Outcomes of PCS patients were compared to coronary artery disease patients (CAD, n=96) to evaluate overall training effectiveness. Results: Training participation was comparable between both groups with no indication of training-specific exercise-induced fatigue. Overall, PCS patients improved significantly by a mean of 6.8±12.1% for W at VT1, 3.1±10.0% for VO2 at VT1, 5.5±14.7% for O2-pulse at VT1, 7.5±15.0% for W at VO2peak, 2.7±11.0% for VO2peak and 4.6±12.4% for O2-pulse at VO2peak (all p<0.05) with no significant differences between groups (p>0.05). Both groups showed reduced levels of fatigue, anxiety and depression as well as improved quality of life and wellbeing (all p<0.05). Compared to guideline-based cardiac rehabilitation, PCS patients showed a similar improvement in workload and oxygen uptake compared to CAD patients. Conclusion: PCS patients benefit from aerobic endurance training, performed as moderate continuous or interval training as part of a medical rehabilitation program in terms of improved physical exercise capacity and disease perception. Results for PCS patients are comparable to guideline-based rehabilitation of CAD patients. Clinical Trial: NCT06016192

Omicron variants have higher infectivity, more immune escape but lower risk of severe clinical outcomes than the ancestral variants. However, people are still wondering whether SARS-CoV-2 may become lethal again or whether some highly-pathogenic strain may emerge in the future. Omicron is more selective proliferation in the upper respiratory tract (URT). The temperature of human URT is 33–34°C, and the virus strains other than Omicron cannot replicate effectively at this temperature. While Omicron adapted to the low temperature environment, so its distribution mainly depends on the expression levels of ACE2 in cells. Similar distribution switch from lungs to URT has been observed for the 1918 H1N1 influenza virus, who vanished after 1921 and has been turned to be the seasonal human influenza A viruses. However, some relatively high-pathogenic SARS-CoV-2 strains and influenza-virus strains may still emerge in the future. Dynamic changes in the viral virulence should be monitored constantly.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

Satellite-based data classification performance remains a challenge for research community in the field of land use/land cover mapping. Here we investigated supervised per-pixel classifications performance under different scenarios, based on single and seasonal multispectral data combi-nations of different sensors (Landsat-8 OLI and Sentinel-2 MSI). In case of Landsat, seasonal spectral indices (EVI and NDMI) were included. A typical Mediterranean watershed with a complex landscape comprised of various forest and wetland ecosystems, crops, artificial surfaces, and lake water was selected to test our approach. All available geospatial data from national databases (Forest Map, LPIS, Natura2000 habitats, cadastral parcels, etc.) are used as ancillary data for clas-sification training and validation. We examined and compared the performance of ML, RF, KNN and SVM classifiers under different scenarios for land use/land cover mapping, according to Copernicus Land Cover (CLC2018) nomenclature. In total, eight land use/land cover classes were identified in Landsat-8 OLI and nine in Sentinel-2a MSI for an acceptable overall accuracy over 85%. A comparison of the overall classification accuracies shows that Sentinel-2a overall accuracy was slightly higher than Landsat-8 (96.68% vs. 93.02%). Respectively, the best-performed algorithm was ML in Sentinel-2 while in Landsat-8 was KNN. However, machine-learning algorithms have similar results regardless the type of sensor. We concluded that best classification performances achieved using seasonal multispectral data. Future research should be oriented towards inte-grating time-series multispectral data of different sensors and geospatial ancillary data for land use/land cover mapping.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has inflicted significant mortality and morbidity worldwide. Continuous virus mutations have led to the emergence of new variants. The Omicron BA.1 sub-lineage prevailed as the dominant variant globally at the beginning of 2022 but was subsequently replaced by BA.2 in numerous countries. Wastewater-based epidemiology (WBE) offers an efficient tool for capturing viral shedding from infected individuals, enabling early detection of potential pandemic outbreaks without relying solely on community cooperation and clinical testing resources. This study integrated RT-qPCR assays for detecting general SARS-CoV-2 and its variants levels in wastewater into a modified triple susceptible-infected-recovered-susceptible (SIRS) model. The emergence of the Omicron-BA.1 variant was observed, replacing the presence of its predecessor, the Delta variant. Comparative analysis between the wastewater data and the modified SIRS model effectively described the BA.1 and subsequent BA.2 waves, with the decline of the Delta variant aligning with its diminished presence below the detection threshold in wastewater. This study demonstrates the potential of WBE as a valuable tool for future pandemics. Furthermore, by analyzing the sensitivity of different variants to model parameters, we are able to deduce real-life values of cross-variant immunity probabilities, emphasizing the asymmetry in their strength.

Background: We studied the outcomes of SARS-CoV-2 (COVID) hospitalizations and their association with myocardial injury and thrombosis. Methods: Retrospective analysis of the National Inpatient Sample 2020 database. Results: We identified 335,799 hospitalizations with COVID. Of these, 1.6% (5,355) were diagnosed with non-ST-segment myocardial infarction (COVNSTEMI). The mean age of COVID hospitalizations was 71.7, with 60.50% being males. The population prevalence included 53.10% Whites, 17.80% Blacks, 19.20% Hispanics, and 4.10% Asians. The average length of stay (LOS) was 10 days, and 37.60% of patients died during their hospitalization. The average cost of hospitalization (TOTCHG) was $156,633. The COVSTEMI group comprised 1,364 cases, with a mean age of 67.4, in-hospital mortality of 47.4%, and the mean TOTCHG was $177,600. The DVTCOV group comprised 2,869 cases, while the PECOV group had 4,828 cases. Male predominance was observed in both groups, with mean ages of 66 years in the DVTCOV group and 64 years in the PECOV group. The DVTCOV group had a LOS of 16 days, with 24.71% mortality, while the PECOV group had a LOS of 11 days, with 19.20% mortality. The average TOTCHG in the DVTCOV group was $248,900, whereas it was $145,378 in the PECOV group. Conclusion: Our study revealed significant mortality rates across different groups, including 38% in COVNSTEMI, 47% in COVSTEMI, 25% in DVTCOV, and 19% in PECOV. These findings highlight the severity of COVID-related complications and the substantial financial burden of hospitalization.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

The study aimed to estimate the prevalence and association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with Type 2 Diabetes Mellitus (T2DM). According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged: 50–80 years) were divided into three groups: Non-sarcopenia (n = 38), Possible Sarcopenia (n = 31, 28.2%), and Sarcopenia (n = 41, 37.3%). Blood samples were collected and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D3 levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, there was a significant association between sarcopenia with BMI, body fat percentage (BF%), and dietary energy and protein intake. Low serum vitamin D3 is a significant risk factor for possible sarcopenia.

Our aim is to provide an insight of the procedures and the dynamics that lead the spread of contagious diseases through populations. Our simulation tool can increase our understanding on the spatial parameters which affect the diffusion of a virus. SIR models are based on the hypothesis that populations are “well mixed”. Our model constitutes an attempt to focus on the effects of the specific distribution of the initially infected individuals through the population and provide insights, considering the stochasticity of the transmission process. For this purpose, we represent the population using a square lattice of nodes. Each node represents an individual that may or may not carry the virus. Nodes that carry the virus can only transfer it to susceptible neighboring nodes. This important revision of the common SIR model provides a very realistic property: the same number of initially infected individuals can lead to multiple paths, depending on their initial distribution in the lattice. This property creates better predictions and probable scenarios to construct a probability function and appropriate confidence intervals. Finally, this structure permits realistic visualizations of the results to understand the procedure of contagion and spread of a disease and the effects of any measures applied.

Abstract: (1) Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) is bidirectional: NAFLD increases the risk of T2DM, and T2DM promotes the progression of the disease to non-alcoholic steatohepatitis (NASH). (2) Material and methods: We performed a retrospective, open study that included 59 patients with NAFLD and T2DM who were distributed into two groups: 44 (74.57%) patients were diagnosed with HS and 15 (25.42%) patients were diagnosed with NASH. (3) Results: Among the non-specific inflammatory biomarkers statistically significant (p=0.003 respectively p=0.03) higher mean values were recorded in patients with NASH and T2DM in the case of ferritin and the neutrophil percentage-to-albumin ratio (NPAR). (4) Conclusions: Consequently, it is essential to identify alternative "surrogate" markers for the inflammatory process, particularly in individuals with diabetes, as it is a key characteristic of NASH. This need arises from the desire to avoid the risks associated with liver biopsy procedures and to prevent the unpredictable and unfavorable progression of NAFLD in patients with T2DM.

The purpose of this work was to longitudinally investigate the dynamic evolution of vaccine hesitancy towards both COVID-19 and influenza. We followed a cohort of 479 adult patients at Udine Hospital (Italy) having in common a medical history of SARS-CoV-2 infection in 2020, during the first and most impactful pandemic wave. Vaccine attitude was assessed through standardized telephone interviews performed at 12 and 18 months after the acute illness. The background of the survey was represented by COVID-19 vaccination campaign, started with the approval of the first vaccine in December 2020 and bolstered by the introduction of Green Pass in July 2021, in a context where anti-vaccination beliefs and mistrust in healthcare system were rising. The first interview reported the success of the 2020/21 seasonal influenza immunization with 46.8% (224/479) of the participants showing a positive attitude, especially the elderly and people with comorbidities (p&lt; 0.001). The investigation conducted at 18 months showed a drastic drop in flu shot acceptance (30/166, 18.1%), the reluctance being justified by the feeling of protection regardless of prevention (55.8%) and by concerns regarding vaccines safety and efficacy (23.3%). In parallel, a great increase in vaccinations against SARS-CoV2 occurred after the introduction of Green Pass (72.9% vs 26.7%), although only a minority of the participants identified in the restrictions induced by the certification the leading incentive to get immunized (22.3%). Vaccine hesitancy remains a dynamic and complex phenomenon, which is difficult to overcome with incentive or obligatory strategies alone. The purpose of achieving vaccine compliance should always take into account the social and political context, as well as the role of personal opinions and emotions.

Heart transplantation is a treatment of choice for patients with severe heart failure. Infection transmission from a donor to a recipient remains a prominent problem in organ transplantation. However, the risk of SARS-CoV-2 transmission through nonlung organ transplantation is still unclear. In the article we present a case of a 28-year-old pregnant woman who developed heart failure soon after recovery from SARS-CoV-2 infection in the third trimester of gestation. In the postpartum period the disease worsened and the patient required cardiac transplantation. We examined the recipient's heart and diagnosed left ventricular noncompaction cardiomyopathy. Immunohistochemical analysis showed the SARS-CoV-2 antigen expression in the donor’s heart before transplantation and after the surgery the endomyocardial biopsy was taken. Moreover, an ultrastructural assessment of the endomyocardial specimen revealed endothelial and pericyte injury and single particles on the surface of endothelium consistent with SARS-CoV-2. Recent findings were associated these damages with SARS-CoV-2 infection. The present study describes the rare case of SARS-CoV-2 transmission from donor to recipient through a heart transplant and resulting in endothelial cell and pericyte activation and humoral immune response activation.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

Personalized recommendation is an important part of ecommerce platform. In the recommendation system, the neural network is used to enhance collaborative filtering to accurately capture user preferences, so as to obtain better recommendation performance. Traditional recommendation methods focused on the results of a single user behavior, ignoring the modeling of multiple interactive behaviors of users, such as click, add to cart and purchase. Although many studies had also focused on Multi-Behavior modeling, two important challenges remained. 1)Since multiple behavioral context information was ignored, it was still a challenge to identify the multimodal relationships of behaviors. 2) Surveillance signals were still sparse. In order to solve this problem, this paper proposes Two-path Multi-behavior Sequence Modeling(TP_MB). First, a two-path learning strategy is introduced to maximize the multiple interaction information of user items learned by the two paths, which effectively enhances the robustness of the model. Second, a multi-behavior dependent encoder is designed. Contextual information is obtained through behavior dependencies in the interaction of different user. In addition, three contrastive learning methods are designed, which not only obtain additional auxiliary supervision signals, but also alleviate the problem of sparse supervision signals. Extensive experiments on two real datasets demonstrate that our method outperforms state-of-the-art multi-behavior recommendation methods.

Type 2 diabetes mellitus may be complicated with chronic complications including diabetic neuropathy (DN). Timely diagnosis is crucial in treatment and maybe reversal of this complication. C reactive protein to albumin ratio (CAR) is considered as a marker of inflammation in various diseases that characterized with acute or chronic inflammation. Since diabetic neuropathy and type 2 diabetes mellitus are also associated with chronic, low grade inflammation, we aimed to study CAR levels of type 2 diabetic subjects with diabetic neuropathy and to compare to those in patients without diabetic neuropathy. Type 2 diabetic patients presented to our institutional outpatient clinics were divided into two according to the presence of DN. Subjects with DN were listed as DN group and others were as non-DN group. Characteristics and laboratory data, including CAR, in DN and non-DN groups were compared. Median CAR of the DN and non-DN groups were 2,19 (0,2-49)% and 0,56 (0,02-5,8)%, respectively (p&lt;0.001). CAR was significantly and positively correlated with age (r=0.15, p&lt;0.001), weight (r=0.19, p=0.01), BMI (r=0.11, p=0.03), waist circumference (r=0.10, p=0.046), fasting plasma glucose (r=0.14, p=0.004), serum creatinine (r=0.25, p&lt;0.001), triglyceride (r=0.17, p&lt;0.001), and LDL-cholesterol (r=0.13, p=0.001) levels. Moreover, CAR was inversely correlated with eGFR levels (r=-0.16, p&lt;0.001). The sensitivity and specificity of CAR (when higher than 1,02%) in predicting diabetic neuropathy were 78% and 73%, respectively (AUC: 0.84, p&lt;0.001, 95% CI: 0,82-0,87). Moreover, high CAR level was an independent risk factor of diabetic neuropathy (p&lt;0.001, OR: 1.34, 95% CI: 0.48-1.62). In conclusion, elevated CAR levels could be considered as a marker of diabetic neuropathy.

Lodging is a common problem in maize production that seriously impacts yield, quality, and the capacity for mechanical harvesting. Evaluation of site-specific lodging risks requires establishment of a method for multi-year monitoring. In this study, spectral images collected by the Sentinel-2 satellite were processed to obtain three types of data: gray-level co-occurrence matrix texture (GLCM), vegetation indices (VIs), and spectral reflectance (SR). Lodging classification models were then established with Random Forest (RF) using each of the three data types separately (the GLCM, VI, and SR models) and in combination (SR+VI model, SR+GLCM model, VI+GLCM mod-el, and SR+VI+GLCM model). By gradually removing features with low importance scores from the SR+VI+GLCM model and analyzing the changes in the overall accuracy (OA), the optimal set of predictive variables was identified and used to construct the optimal model. A model built us-ing data from a single timepoint in 2021 was tested on data collected at a similar timepoint in 2019 and vice versa to assess interannual model generalizability. The results of this study demon-strate that for monitoring maize lodging, models constructed with a single feature type, the GLCM model had significantly lower accuracy compared to the VI and SR models. During certain growth stages, the model constructed with combined features had significantly higher accuracy in monitoring maize lodging compared to models constructed with a single feature. During the pro-cess of selecting the optimal predictive variables, it was found that the accuracy of the model did not increase as the number of predictive variables increased. The results show that the positive and negative validation models had an accuracy of 96.55% and 95.18%, with kappa values of 0.93 and 0.83, respectively. This indicates that the model has strong generality for the same repro-ductive stage between years. This study provides a detailed method for large-scale maize lodging monitoring, allowing for identification of optimal planting practices to reduce the probability of lodging and ultimately improving regional maize yield and quality.

Background: The outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in the global COVID-19 pandemic. The urgency for an effective SARS-CoV-2 vaccine has led to the development of a first series of vaccines at unprecedented speed. The discovery of SARS-CoV-2 spike-glycoprotein mutants, however, and consequentially the potential to escape vaccine-induced protection and increased infectivity, demonstrates the persisting importance of monitoring SARS-CoV-2 mutations to enable early detection and tracking of genomic variants of concern. Results: We developed the CoVigator tool with three components: 1) a knowledge base that collects new SARS-CoV-2 genomic data, processes it and stores its results; 2) a comprehensive variant calling pipeline; 3) an interactive dashboard highlighting the most relevant findings. The knowledge base routinely downloads and processes virus genome assemblies or raw sequenc-ing data from the COVID-19 Data Portal (C19DP) and the European Nucleotide Archive (ENA), respectively. The results of the variant calling pipeline are visualized through the dashboard in the form of tables and customizable graphs, making it a versatile tool for tracking SARS-CoV-2 variants. We put a special emphasis on the identification of intrahost mutations and make available to the community what is, to the best of our knowledge, the largest dataset on SARS-CoV-2 intrahost mutations. In the spirit of open data, all CoVigator results are available for download. The CoVigator dashboard is accessible via covigator.tron-mainz.de. Conclusion: With increasing demand worldwide in genome surveillance for tracking the spread of SARS-CoV-2, CoVigator will be a valuable resource of up-to-date list of mutations, which can be incorporated into global efforts to sustainably prevent or treat infections.

Cardiac damage has been attributed to SARS-Cov-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population.

Cancer is a complex disease, considered a major public health problem worldwide. Among the types of cancer, melanoma, and leukemias present high mortality rates in Brazil and worldwide. Currently, conventional cytotoxic treatments cause severe side effects by the non-selectivity between normal cells and cancer cells. Therefore, molecules of natural origin with more efficient anticancer properties and that present fewer adverse effects are of extreme importance for cancer therapy and improvement in patients’ quality of life. This study isolated, identified, and characterized the chemical structure of a new anthraquinone present in the extract of the roots of Senna velutina. In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina, analyzed by HPLC-DAD, and its molecular structure was determined by NMR. Subsequently, their cytotoxic activity was evaluated by the MTT method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. By flow cytometry technique, the apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2'-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2'-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and CA+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed-cell death pathways induced by 2'-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2'-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.

Foxtail millet (Setaria italica (L.) P. Beauv) is an important food and forage crop that is well adapted to nutrient-poor soils. However, little is known about how foxtail millet adapts to low nitrogen (LN) at the physiological and molecular levels. In the present study, two foxtail millet varieties with contrasting low nitrogen (LN) tolerance properties were investigated through integrative analyses of physiological featureparameters and transcriptomics. The physiological results showed that JG20 (high tolerance to LN) had higher biomass accumulation, nitrogen content and nitrogen use efficiency compared with JG22 (low tolerancesensitive to LN) under LN. JG20 had higher soluble sugar and soluble protein concentration in shoots compared with JG22 under LN, while contcentrations of soluble sugar and soluble protein contents were higher in the roots of JG22. Higher levels of CTK contentzeatin concentration were found in the shoots of JG20 com-pared with JG22, and a higher ABA contcentration was found in both the shoots and roots of JG22 compared with JG20 under LN. In the transcriptomics results, JG20 had more differentially ex-pressed genes (DEGs) than JG22 both in shoots and roots in response to LN. These LN-responsive genes were enriched in glycolysis, starch and sucrose metabolism, photosynthesis, biosynthesis of amino acids, hormone metabolism and nitrogen metabolism. Furthermore, the high-affinity nitrate transporter gene, SiNRT2.1, and glutamine synthetase gene, SiGS5, chlorophyll apoprotein of photosystem II gene, SiPsbQ, ATP synthase subunit gene, b, auxin-responsive protein gene, SiIAA25, and aldose 1-epimerase gene, SiAEP, in shoots, and high-affinity nitrate transporter gene, SiNRT2.3, SiNRT2.4, and glutamate synthase gene, SiGOGAT2, auxin-responsive protein gene, SiIAA4, fructose-bisphosphate aldolase gene, SiAEP5, in root, were important genes in-volved in the LN tolerance of foxtail millet. These results provide a detailed description of the physiological and transcriptome response of foxtail millet under LN condition.

Vaccines are crucial for controlling the COVID-19 pandemic, and booster doses are becoming increasingly important. This study aimed to assess the efficacy of the ChAdOx1 nCoV-19 vaccine from AstraZeneca as a third dose in healthcare workers at different time intervals (one, three, and six months). Two methods to measure immune response—ELISA (EUROIMMUN Medizinische Labordiagnostika AG, Luebeck, Germany) and ELISpot (Mabtech AB, Macka Strand, Sweden)—were used. A total of 170 participants were included in the study. The results showed that while IgG levels decreased at six months compared to levels at one and three months, they were still significantly higher than the baseline. Furthermore, neutralizing levels at three and six months after the third dose were not significantly different. These findings suggest that the immune response induced by the vaccine is robust and effective for several months. These results have significant implications for public health policymakers, as they provide strong support for booster vaccinations. The ChAdOx1 nCoV-19 vaccine appears to be a reliable option for preventing the spread of COVID-19, and this study provides valuable information for healthcare workers and policymakers in managing the pandemic.

The characteristics of the Sentinel-2 mission with a decametric resolution and frequent acquisitions allow to improve the identification of crops. The majority of the studies on crop classification using RS were targeted at herbaceous and gramineous crop classes while fewer results were obtained on woody crops which present a strong variability in management practices that make their identification difficult. Thus, this study aimed to propose a rapid, accurate, and cost-effective analytical approach for the delineation of fruit orchards (OC), vineyards (VY), and olive groves (OL) in the Mediterranean (Southern France) considering two locations. A classification based on phenology metrics (PM) de-rived from temporal Sentinel-2 time series was developed to perform the classification. The PM were computed by fitting a double logistic model on temporal profiles of vegeta-tion indices to delineate OC, VY, and a DC class gathering all remaining surfaces. The generated PM were introduced in a random forest (RF) algorithm to identify woody crops across the two sites. The method was tested on different vegetation indices, the best results being obtained with the leaf area index (LAI). To delineate OL in the DC class, the tem-poral features of the green chlorophyll vegetation index (GCVI) were found to be the most appropriated with a typical drop of the signal during the mid-season (DOY 150-250). As a final result, we obtained an overall accuracy ranging from 89-96% and Kappa of 0.86-0.95 by considering each study site and year (2016-2021), separately. This accuracy is much better than applying the RF algorithm on the LAI times series, which led to a Kappa rang-ing between 0.3 and 0.52 and demonstrates the interest of using phenological traits rather than the raw time series of the RS data. The method can be well reproduced from one year to another. Moreover, it is possible to apply the classification model of a given year to an-other, keeping good accuracy. This is an interesting feature to reduce the burden of col-lecting ground truth information. On the contrary, the use of a classification model cali-brated in one site and applied to another led to a strong degradation of the classification accuracy. Woody crop phenology is dependent on site climatic conditions as well as the cultivar and management practices that can differ from one site to another.

Due to the health crisis caused by SARS-CoV-2, the creation of a new vaccine platform based on mRNA was implemented. Globally, around 13.32 billion COVID-19 vaccine doses of diverse platforms have been given, and up to this date, 69.7% of the total population received at least one injection of a COVID-19 vaccine. Although these vaccines prevent hospitalization and severe forms of the disease, increasing evidence has shown they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Recent research has also raised concerns that mRNA vaccines could induce immune tolerance, which, added to that caused by the virus itself, could complicate the clinical course of a COVID-19 infection. Furthermore, recent investigations have found high IgG4 levels in people who were administered two or more injections of mRNA vaccines. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. Altogether, evidence suggests that the reported increase in the IgG4 levels detected after repeated vaccination with the mRNA vaccines is not a protective mechanism; rather, it may be a part of the immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. IgG4-induced suppression of the immune system due to repeated vaccination can also cause autoimmune diseases, promotes cancer growth, and autoimmune myocarditis in susceptible individuals.

This study aimed to investigate the possibility of using one-shot hyperspectral airborne images to recognize crops for an area with many small plots. The results showed that unsupervised clustering methods could classify crops with an accuracy of 80%, which improved to 90% when restricted to only grain crops, using a single airborne hyperspectral recording. However, additional layers such as NDVI, DTM, slope, and aspect did not improve classification accuracy. For comparison, the accuracy of clustering time series Sentinel-2 images with NDVI layers and DTM-derived data yielded an accuracy of: 74% ,Sentinel-2 time series 68% and single one registration before harvest - 39%. The results of the random forest classification were slightly less accurate due to a lack of sufficient reference data. However, it is challenging to verify the reported accuracy of crop recognition in the literature above 90% due to differences in analysis methodologies, reference data selection, pixel/object approaches, metric choice, and calculation formulas used.

The reaction of mercaptoacetic acid esters with pentachloro-2-nitro-1,3-butadiene provides appropriate precursors for the synthesis of 2,3,4-trisubstituted benzo[h]quinolines. These heterocycles are easily accessible via a single-step reaction with 1-naphthyl- or 1-anthracenylamine, respectively. Due to steric bulk and high electron density ring closure to benzo[h]quinolines takes place, exclusively. Such highly substituted annelated pyridine systems can be modified in subsequent, selective reactions to build up new N-heterocycles with promising microbiological properties. Antibacterial and antiproliferative assays against four cell mammalian cell lines demonstrate that some of the sulfur-substituted benzo[h]quinolines analogs display potent phenotypic bioactivities in the single-digit micromolar range.

The effects of morphine (MOR) and dexmedetomidine (DEX) on the MAC of isoflurane were measured in rats chronically treated with the synthetic cannabinoid WIN 55,212-2 (WIN55). Methods: The MAC of isoflurane was determined in 32 male rats from expiratory samples at the time of tail clamping. The effects of morphine (MAC(ISO+MOR)) and dexmedetomidine (MAC(ISO+DEX)) on the MAC of isoflurane in untreated rats and rats treated for 21 days with WIN 55,212-2 (MAC(ISO+WIN55+MOR)) and (MAC(ISO+WIN55+DEX)) were measured. Prior to the administration of morphine and dexmedetomidine, the MAC of the isoflurane was measured in both untreated rats (MAC(ISO)) and those treated with WIN 55,212-2 (MAC(ISO+WIN55)). Results: The minimum alveolar concentration was measured as 1.32 ± 0.06 in the MAC(ISO) group and 1.69 ± 0.09 in the MAC(ISO+WIN55) group. The MAC of the MAC(ISO+MOR) group was 0.97 ± 0.02 (26% less than the control group, MAC(ISO)). MAC was measured as 1.55 ± 0.08 in the MAC(ISO+WIN55+MOR) group (8% less than the MAC(ISO+WIN55) group), 0.68 ± 0.10 in the MAC(ISO+DEX) group (48% less than the control group, MAC(ISO)), and 0.67 ± 0.08 in the MAC(ISO+WIN55+DEX) group (60% less than the MAC(ISO+WIN55) group). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. The sparing effect on isoflurane of morphine decreases in rats chronically treated with the synthetic cannabinoid, WIN 55,212-2. Dexmedetomidine increases its sparing effect on the minimum alveolar concentration of isoflurane in rats chronically treated with WIN 55,212-2.

The novel coronavirus disease 19 (COVID-19) has resulted in an estimated 20 million excess deaths and the recent resurgence of COVID-19 in China is predicted to result in up to 1 million deaths over the next few months. With vaccines unable to halt transmission it is important to continue our quest for safe, effective, affordable drugs that will be available to all countries. Drug repurposing is one of the strategies being explored in this context. Recently, out of 7,817 approved drugs, 214 candidates were systematically down-selected using a combination of 11 filters including approval status, assay data against SARS-CoV-2, pharmacokinetic, pharmacodynamic and toxicity profiles. These drugs were subjected in this study to virtual screening against various targets of SARS-CoV-2 followed by molecular dynamic studies of the best scoring ligands against each target. The chosen molecular targets were Spike receptor binding domain, Nucleocapsid protein RNA binding domain, and key non-structural proteins 3, 5, 12, 13 and 14. Four drugs approved for other indications — alendronate, cromolyn, natamycin and treprostinil — look sufficiently promising from our in silicostudies to warrant further in vitro and in vivo investigations as appropriate to ascertain their extent of anti-viral activities.

Live attenuated vaccines have through history proved themselves as safe and efficient. Pasteur has developed a vaccine against rabies, through a long process of passage of the virus wild type through rabbits. The result was one of the most efficient attenuated live-virus vaccines. This paper suggests a method based on calculations of biothermodynamic properties of potential tissues for vaccine application, predilected host tissue and virus wild type. Gibbs energy of biosynthesis represents the thermodynamic driving force for virus multiplication. The attenuated strain of the virus should possess Gibbs energy of biosynthesis, which is less negative than the predilected target tissue, but more negative than the vaccine portal tissue. In that way, the attenuated virus strain should be able to multiply in the vaccine portal of entry tissue and cause an immune response, making it efficient. On the other hand, the attenuated strain cannot multiply in the predilected host tissue, making it safe. The attenuation is achieved by adding a gene to the virus, which encodes a ballast protein. Production of the ballast protein would make virus multiplication less favorable, since it would require energy, but be useless to the virus.

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants for mutual benefits. The interactions with a host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. Ethyl acetate extract from isolated A. flavus showed significant cytostatic effects (IC50: 16.25 μg mL−1) against breast cancer cells (MCF-7). Morphology of cells and DAPI stained nuclei along with the results of flow cytometry annexin V/PI assay suggested apoptosis to be the main process leading to cells’ death. While investigating the mechanism that triggers apoptosis, we found that the extract of A. flavus increased ROS generation and caused loss of mitochondrial membrane potential of MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was examined using gas chromatography-mass spectrometry (GC-MS). Interestingly, nine phytochemicals were found to have potential inhibitory effects of anti-apoptotic protein (Bcl-2) in the breast cancer cells. In the in silico molecular docking and molecular dynamics simulation studies revealed that two compounds: 2,4,7-Trinitrofluorenone and 3alpha, 5alpha-Cyclo-ergosta-7,9(11),22t-triene-6beta-ol exhibited significant binding affinities (-9.20, and -9.50 Kcal mol-1, respectively) against Bcl-2 along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer.

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track virus genetic changes that drive the early evolutionary dynamics of the Omicron. Based on the Omicron dataset chosen for the improved temporal signals and sampled globally between November 2021 and January 2022, most recent common ancestor (tMRCA) and substitution rates for BA.1 were estimated to be 18 September 2021 (95% highest posterior density (HPD) 04 August – 22 October 2021) and 1.435×10-3 (95% HPD = 1.021×10-3 – 1.869×10-3) substitution/site/year, respectively, whereas 03 November 2021 (95% highest posterior density (HPD) 26 September – 28 November 2021) and 1.074×10-3 (95% HPD = 6.444×10-4 – 1.586×10-3) substitution/site/year for BA.2 sub-lineage. The findings of this study suggest that the Omicron BA.1 and BA.2 sub-lineages originated independently and evolved over time. Furthermore, we identified multiple sites in spike protein undergoing continued diversifying selection that may alter the neutralization profile of BA.1. This study shed light on the ongoing global genomic surveillance and Bayesian molecular dating analyses to better understand the evolutionary dynamics the virus and, as a result, mitigate the impact of emerging variants on public health.

Acute SARS-CoV-2 infections in children and adolescents are usually mild. However, they can suffer from ongoing symptoms generally referred as long COVID. Sleep disorders are one of the most frequent complaints in long COVID although precise data are missing. We assessed the sleep behavior of children and adolescents who presented at our outpatient clinic between January 2021 and May 2022 with the Children's Sleep Habits Questionnaire (CSHQ-DE). We compared sleep behavior at three different time points: pre-COVID-19, post-COVID-19 at initial presentation and post-COVID-19 at re-presentation. Data from 45 patients were analyzed. Of those, 64% were female and the median age was 10 years (range 0-18 years). Asymptomatic or mild COVID-19 disease was experienced in 89% of patients, whilst 11% experienced moderate disease. Initial presentation occurred at a median of 20.4 weeks (6 weeks - 14 months) after infection. The CSHQ-DE score increased significantly from pre-COVID-19 (45.82+8.7 points) to post-COVID-19 (49.40+8.3 points; p=&lt;0.01). The score then normalized at re-presentation (46.98+7.8; p=0.1). The greatest changes were seen in the CSHQ-DE subscale score "daytime sleepiness". Our data show that children and adolescents with long COVID often suffer from sleep disturbance. For most children and adolescents these sleep disorders decreased over time without further medical intervention, aside from a basic sleep consultation.

We recently proposed that topological quantum computing might be based on $SL(2,\mathbb{C})$ representations of the fundamental group $\pi_1(S^3\setminus K)$ for the complement of a link $K$ in the $3$-sphere. The restriction to links whose associated $SL(2,\mathbb{C})$ character variety $\mathcal{V}$ contains a Fricke surface $\kappa_d=xyz -x^2-y^2-z^2+d$ is desirable due to the connection of Fricke spaces to elementary topology. Taking $K$ as the Hopf link $L2a1$, one of the three arithmetic two-bridge links [the Whitehead link $5_1^2$, the Berge link $6_2^2$, the double-eight link $6_3^2$] or the link $7_3^2$, the $\mathcal{V}$ for those links contains the reducible component $\kappa_4$, the so-called Cayley cubic. In addition, the $\mathcal{V}$ for the later two links contains the irreducible component $\kappa_3$, or $\kappa_2$, respectively. Taking $\rho$ to be a representation with character $\kappa_d$ ($d<4$), with $|x|,|y|,|z| \le 2$, then $\rho(\pi_1)$ fixes a unique point in the hyperbolic space $\mathcal{H}_3$ and is conjugate to a $SU(2)$ representation (a qubit). Even though details on the physical implementation remain open, more generally, we show that topological quantum computing may be developed from the point of view of three-bridge links, the topology of the $4$-punctured sphere and Painlev\'e VI equation. The $0$-surgery on the $3$ circles of the Borromean rings L6a4 is taken as an example.

Omicron BA.2.75 may become the next globally dominant strain of COVID-19 in 2022. BA.2.75 sub-variant has acquired more mutations (9) in spike protein and other genes of SARS-CoV-2 than any other variant. Thus, its chemical composition and thermodynamic properties have changed comparing to earlier variants. In this paper Gibbs energy of binding and antigen-receptor binding rate is reported for the BA.2.75 variant. Gibbs energy of binding (driving force of binding) of Omicron BA.2.75 variant is more negative than that of the competing variants BA.2 and BA.5.

Observing cultivated crops and other forms of land use is an important environmental and economic concern for agricultural land management and crop classification. Crop categorization offers significant crop management data, ensuring food security, and developing agricultural policies. Remote sensing data, especially publicly available Sentinel 1 and 2 data, has effectively been used in crop mapping and classification in cloudy places because of their high spatial and temporal resolution. This study aimed to improve crop type classification by combining Sentinel-1 (Synthetic Aperture Rader (SAR)) data and the Sentinel-2 Multispectral Instrument (MSI) data. In the study, Random Forest (RF) and Classification and Regression Trees (CART) classier were used to classify grain crops (Barley and Wheat). The classification results based on the combination of Sentinel-2 and Sentinel-1 data indicated an overall accuracy (OA) of 93 % and a kappa coefficient (K) of 0.896 for RF and (89.15%, 0.84) for the CART classifier. It is suggested to employ a mix of radar and optical data to attain the highest level of classification accuracy since doing so improves the likelihood that the details will be observed in comparison to the single-sensor classification technique and yields more accurate results.

Abstract. Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Fifty-five SARS-CoV-2 positive and 61 negative third trimester patients were randomly selected from Montefiore Medical Center (MMC), Bronx, NY. In addition, two positive cases from Yale New Haven Hospital, CT were included as controls. All 55 placentas delivered by SARS-CoV-2 positive mothers were uninfected by the virus, based on immunohistochemistry, in-situ hybridization, and qPCR analysis. However, placental villous infarcts, mild preeclampsia, shortened gestational periods and lower Apgar scores were observed in the infected cases. These findings suggest that even without entering the placenta, SARS-CoV-2 can affect various systemic pathways culminating in altered placental development and function, which may adversely affect the fetus, especially in a high-risk patient population such as ours. These results underline the importance of vaccination among pregnant women, particularly in low resource areas.

Background: Some patients who have recovered from COVID-19 have experienced a range of persistent symptoms or the appearance of new ones after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. Methods: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (&lt; 2,500 m) and high altitude (&gt;2,500 m).Results: Overall, 1100 (52.3%) responders claimed to have long-term symptoms after SARS-CoV-2 infection. Most of these symptoms were reported by women (64.0%), the most affected group was young adults (68.5%), and the majority of long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of persisting symptoms was observed among those who received an incomplete vaccine scheme.Conclusions: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 20-40, are more likely to describe sequalae associated with post-COVID. We also found that living at a high altitude was associated with earlier onset and longer symptom duration. Finally, we found a greater risk to report long lasting symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.

The evolution and the emergence of new mutations of viruses affect their transmissibility and/or pathogenicity features, depending on different evolutionary scenarios of virus adaptation to the host. A typical trade-off scenario of SARS-CoV-2 evolution has been proposed, which leads to the appearance of an Omicron strain with lowered lethality, yet enhanced transmissibility. This direction of evolution might be partly explained by virus adaptation to therapeutic agents and enhanced escape from vaccine-induced and natural immunity formed by other SARS-CoV-2 strains. Omicron’s high mutation rate in the Spike protein, as well as its previously described high genome mutation rate (Kandeel et al., 2021), revealed a gap between it and other SARS-CoV-2 strains, indicating the absence of a transitional evolutionary form to the Omicron strain. Therefore, Omicron has emerged as a new serotype and divergent from the evolutionary lineage of other SARS-CoV-2 strains. Omicron is a rapidly evolving variant of high concern, whose new subvariants continue to manifest. Its further understanding and the further monitoring of key mutations that provide virus immune escape and/or high affinity towards the receptor could be useful for vaccine and therapeutic development in order to control the evolutionary direction of the COVID-19 pandemic.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Evaluation of the usefulness of [18F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of findings with clinical prognostic markers. Prospective study included 20 patients admitted to hospital with COVID-19 pneumonia between November 2020 and March 2021. Clinical and laboratory test findings were gathered at admission, 48-72h post-admission, and 2-3 months post-discharge. [18F]FDG-PET/CT and respiratory function tests were performed at 2-3 months post-discharge. Lung volumes (TLC), spirometry (FVC, FEV1), lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. PET/CT images were qualitatively and semi-quantitatively interpreted. Volumetric [18F]FDG-PET/CT results were correlated with laboratory test and respiratory parameters. Eleven [18F]FDG-PET/CT (55%) were positive. The main finding was hypermetabolic lymphade-nopathy in the mediastinum (90.9%). SUVpeak of the target mediastinum lesion was correlated with neutrophil and lymphocyte counts. Eleven (55%) patients had impaired respiratory function, most frequently a reduced DLCO (35%). SUVpeak was positively correlated with %predict-ed-DLCO values. Pulmonary TLG was negatively correlated with %predicted-DLCO and TLC values. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [18F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients.