Non-enzymatic thiol addition into α,ß-unsaturated carbonyl system is associated with several biological effects. In vivo, the reactions can form small-molecule thiol (e.g., glutathione) or protein thiol adducts. The reaction of two synthetic (4’-methyl- and 4’-methoxy substituted) cyclic chalcone analogs with glutathione and N-acetylcysteine was studied by HPLC-UV method. The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The structure of the formed adducts was confirmed by HPLC-MS. The incubations were performed under three different pH conditions (pH 3.5/3.8, 6.3/6.7, and 8.0/7.4). The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended on the substitution and the pH. The frontier molecular orbitals and the Fukui function were carried out to investigate the effects on open-chain and seven-membered cyclic analogs. Furthermore, machine learning protocols were used to provide more insights into physicochemical properties and to support the different thiol-reactivity. HPLC analysis indicated diastereoselectivity of the reactions. The observed reactivities do not directly relate to the different in vitro cancer cell cytotoxicity of the compounds.

Non-enzyme-catalyzed thiol addition onto the α,β-unsaturated carbonyl system is associated with several biological effects. Kinetics and diastereoselectivity of non-enzyme catalyzed nucleophilic addition of GSH and NAC to the six-membered cyclic chalcone analogs 2a and 2b were investigated at different pH values (pH 3.2, 7.4 and 8.0). The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended both on the substitution and the pH. The stereochemical outcome of the reactions was evaluated by HPLC-UV method. The structure of the formed thiol-conjugates and the retro-Michael products (Z)-2a and (Z)-2b were confirmed by HPLC-MS. The frontier molecular orbitals and the Fukui function were carried out to investigate their effects on the six-membered cyclic analogs. Data were compared with those obtained with the open-chain (1) and the seven-membered (3) analogs. The observed reactivities do not directly relate to the difference in in vitro cancer cell cytotoxicity of the compounds.

The zebrafish Danio rerio is suitable to study gametes as a model organism. There were > 70% of zebrafish spermatozoa activated, because they were contaminated with urine or excrement. The movement of spermatozoon in water was propagated along the flagellum at 16 s after sperm activation, then damped from the end of the flagellum for 35 s and fully disappear at 61 s after activation. For artificial fertilization, milt must be added to an extender, which stops the movement of sperm and keeps the sperm motionless until fertilization. E400 was shown to be the most suitable extender as it allows to store sperm for fertilization for 6 to 12 h at 0-2oC. Sperm motility decreased only to 36% at 12 h post stripping (HPS) for E400 extender and to 19% for Kurokura extender. To achieve an optimal level of fertilization and hatching, a test tube with a well-defined amount of 6,000,000 spermatozoa in E400 extender per 100 eggs and 100 µl of activation solution has proved to be more successful than using a Petri dish. The highest fertilization and hatching rates reached 80% and 40-60%, respectively, with milt stored for 1.5 h in E400 extender at 0-2oC.

We propose a generalization of Nambu-Hamilton equation in superspace $\mathbb R^{3|2}$ with three real and two Grassmann coordinates. We construct the even degree vector field in the superspace $\mathbb R^{3|2}$ by means of the right-hand sides of proposed generalization of Nambu-Hamilton equation and show that this vector field is divergenceless in superspace. Then we show that our generalization of Nambu-Hamilton equation in superspace leads to family of ternary brackets of even degree functions defined with the help of Berezinian. This family of ternary brackets is parametrized by the infinite dimensional group of invertible second order matrices, whose entries are differentiable functions on the space $\mathbb R^{3}$. We study the structure of ternary bracket in a more general case of a superspace $\mathbb R^{n|2}$ with $n$ real and two Grassmann coordinates and show that for any invertible second order functional matrix it splits into the sum of two ternary brackets, where one is usual Nambu-Poisson bracket, extended in a natural way to even degree functions in a superspace $\mathbb R^{n|2}$, and the second is a new ternary bracket, which we call $\Psi$-bracket, where $\Psi$ can be identified with invertible second order functional matrix. We prove that ternary $\Psi$-bracket as well as the whole ternary bracket (the sum of $\Psi$-bracket with usual Nambu-Poisson bracket) is totally skew-symmetric, satisfies the Leibniz rule and the Filippov-Jacobi identity (Fundamental Identity).

: This study was conducted to evaluate the behavior of nitrate, moisture and organic matter in a soil with low agronomic input. The test was conducted on silty-sandy soil, a temporal variability of the variables in the different seasons was observed in the three theses. The theses were observed in parallel twice a week. Nitrates showed an increase during the summer-autumn season with higher values ​​in the thesis containing organic matter, “bare soil” followed by the thesis “fallow” and finally by the “cultivated” (see below in experimental set up). The humidity was higher in the “bare soil” thesis followed by “fallow” and “cultivated” one during the summer, in winter the “cultivated” showed the lowest humidity compared to the other two theses. The organic matter does not show great variability in the seasons but is higher in the “fallow” thesis followed by “bare soil” and “cultivated” one. The Montecarlo test informed us that organic matter and humidity were autocorrelated within 5-7.5 m of distance (10-15 lag) while nitrates even if they seemed to be not autocorrelated with each other and have a cyclical pattern.

Film therapy, the therapeutic use of movies in psychological therapies, is a growing area of interest to therapists and researchers. This paper presents the MOVIE model of film therapy, a widely applicable, trauma-informed framework for working with film imagery and themes in individual or group therapy, counsellor education and self-help. Film or cinema therapy is a highly accessible and relatable method for many diverse client and student groups with benefits that include, catharsis and emotional processing, greater ease of dialogue around issues, increased empathy, and interpersonal learning, engaging with new perspectives and learning skills. Following the model clients mindfully observe and voice their emotional and psychological responses to movie watching, identify how the imagery, characters, themes, and narrative symbolise personal experience and consider any new possibilities that emerged through re-authoring personal narratives. The model is informed by a practice focused review of literature.

Through the use of machine learning algorithms like the Support Vector Machine, it has been show that burn extent can be accurately mapped from hyperspatial drone imagery in both grasslands and forests. Despite these successes, hyperspatial imagery must be acquired via drones, requiring large amounts of time and resources to capture areas much smaller than the large catastrophic fires which result in the majority of the lands burned each year by wildland fires. To overcome this difficulty, high spatial resolution satellite imagery from Worldview2 can be substituted for hyperspatial drone imagery, allowing for larger regions of images to be acquired more easily and efficiently. Additionally, Worldview2 trades spatial resolution for spectral resolution and extent, capturing images in 8 multispectral bands as opposed to 3 band imagery in the visible spectra. This research examines the utility of each of the 8 bands observed in Worldview2 imagery using an Iterative Dichotomiser 3 decision tree, then uses these bands to map burn extent and biomass consumption. Several classifications of burn extent and biomass consumption are produced and compared based on the bands used as inputs. The results show that using Worldview2 imagery to map burn extent and biomass consumption results in highly accurate maps, with slight improvements when additional bands are added.

The paper examines the impact of inward remittances flows on per capita GDP growth in Bangladesh during 1976-2012. We find that the growth effect of remittances is negative at first but becomes positive at a later stage, an evidence of a non-linear. Unproductive use of remittances was rampant in the beginning when they were received by migrant families but better social and economic investments led to more productive utilisation of remittances receipts at later periods. This was the possible mechanism behind the U-shaped relationship. Unlike what is suggested in the literature that the effect of remittances is more pronounced in a less financially developed economy, our evidence do not show that the effect of remittances on per capita GDP growth in Bangladesh is conditional on the level of financial development.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

The emphasis in the automotive industry towards sustainable mobility has led to a significant interest in hybrid-electric propulsion systems with high energy density batteries. Addressing the needs of this strategy, the battery market is exploring new technologies to improve the safety and lifespan of electric vehicles. To this end, there is a focus on the all-solid-state battery (ASSB) technology for its cycle capabilities. Filling the current void in the literature pertaining to accurate ageing models for ASSBs, in this work, we present an enhanced version of the numerical ageing model, originally developed for liquid electrolyte based batteries, to forecast the development of the solid electrolyte interface layer that is the major cause of battery capacity fading. The model has been tested on prototype batteries and reveals an accuracy of 99%. The capacity fade in ASSBs has been investigated under different conditions, and the enhanced ageing model has been validated using experimental data from these batteries. The findings suggest that there is potential for solid-state batteries to be commercialized, although significant work is needed to match the manufacturing level of lithium-ion batteries with liquid electrolytes.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of <1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

The term “conservation,” as it relates to biodiversity in a Western context, has a storied past and as conservation science and societal values have evolved, consensus over its precise meaning has remained elusive. The broad scope of contemporary definitions hampers effective communication during a period of environmental crisis and is troublesome for any derivative concept which aims to empirically quantify the efforts of the conservation sector. This presents an avoidable hindrance to the systematic planning of the conservation field. To help remedy this situation, we provide an outcome separation framework that is based on the expected degree of separation between an action’s proximate outcome, from its intended, ultimate outcome for a habitat and/or species. Framing a definition of conservation through this lens of outcome separation allows for conservation-related actions to be clearly categorized into one of three discrete tiers: primary, secondary, and tertiary. A distillation of this tiered framework also provides a new definition of biodiversity conservation that is more rigorous and adaptable to future conceptual evolutions of the field.

The Mazenod Lake region of the southern Great Bear Magmatic Zone (GBMZ) of the Northwest Territories, Canada comprises the north-central portion of the Faber volcano-plutonic belt. Mazenod geology is dominated by rhyodacite to basaltic-andesite ignimbrite sheets with interlayered volcaniclastic sedimentary rocks dominated by fine-grained laminated tuff sequences. Much of the intermediate to mafic nature of volcanic rocks is disguised by low-intensity but pervasive metasomatism. The region is affected by a series of coalescing magmatic-hydrothermal systems that host the Sue-Dianne magnetite-hematite IOCG deposit and several related showings including magnetite, skarn, and IOA styles of alteration ± mineralization. Exposed at surface are dominantly mid to upper levels of these systems, with underlying batholith, pluton and stocks exposed along the periphery, as well as locally within volcanic rocks associated with more intense alteration and mineralization. Widespread alteration includes potassic and sodic metasomatism, and silicification with structurally controlled giant quartz complexes. Localized tourmaline, skarn, magnetite-actinolite, and iron-oxides occur within structural breccias, and where most intense formed the Sue-Dianne Cu-Ag-Au diatreme-like breccia deposit. Magmatism, volcanism, hydrothermal alteration and mineralization formed during a negative tectonic inversion within the Wopmay Orogen. This generated a series of oblique offset rifted basins with continental style arc magmatism and extensional structures unique to GBMZ rifting. All significant hydrothermal centres in the Mazenod region occur along and at the intersections of crustal faults either unique to or put under tension during the GBMZ inversion.

Helical (frontier) molecular orbitals [Chem. Sci. 2013, 4, 4278] have been reported almost a decade ago. Yet, helical molecular spin densities [Mol. Phys. 2022, e2157774] have been observed by us only very recently. In this work, we have observed that some chiral boron clusters (B–16, B–20, B–24, and B–28) can simultaneously have helical molecular orbitals and helical spin densities. To our best knowledge, it is the first time we have discovered that inorganic boron clusters assume such an unprecedented property. We have unambiguously unraveled that it is chiral Jahn-Teller distortion of quasi-planar boron clusters that drives the formation of helical molecular spin densities. More interestingly, we have shown that elongation/enhancement of helical molecular orbitals can be achieved by simply adding more building blocks via a linker. Aromaticity properties of these boron clusters are also discussed. Implication of this work is straightforward that boron clusters may find potential applications in spintronics, such as molecular magnets.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

Managing a portfolio whose value closely tracks an index by trading only in a subset of the index constituents involves an NP-hard optimisation problem. In the prior literature, it has been suggested to solve this problem using sequential Monte Carlo (SMC, a.k.a. particle filter) methods. However, this literature does not take transaction costs into account, although transaction costs are the primary motivation for attempting to replicate the index by trading in a subset, rather than the full set of index constituents. This paper extends the SMC approach to index tracking to allow for proportional transaction costs and implements this extended method on empirical data for a variety stock indices. In addition to providing a more practically useful tracking strategy by allowing for transaction costs, we find that including a penalty for transaction costs in the optimisation objective can actually lead to better tracking performance.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Since its initial development in the 1970’s by Phil Burke and his collaborators, the R-matrix theory and associated computer codes have become the de facto approach for the calculation of accurate data for general electron-atom/ion/molecule collision and photoionization processes. The use of a non-orthonormal set of orbitals based on B-splines, now called the B-spline R-matrix (BSR) approach, was pioneered by Zatsarinny. It has considerably extended the flexibility of the approach and improved particularly the treatment of complex many-electron atomic and ionic targets, for which accurate data are needed in many modelling applications for processes involving low-temperature plasmas. Both the original R-matrix approach and the BSR method have been extended to the interaction of short, intense electromagnetic (EM) radiation with atoms and molecules. Here we provide an overview of the theoretical tools that were required to facilitate the extension of the theory to the time domain. As an example of a practical application, we show results for two-photon ionization of argon by intense short-pulse extreme ultraviolet radiation

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer's disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion dis-ease, or brain tumors. Diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theranostic applications to meet these needs. This review covers pioneer studies to apply aptamers, which show promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

Sarcomas are a heterogenous group of tumours that commonly carry poor prognosis with limited therapeutic options. Adolescents and young adults (AYA) with sarcoma are a unique and under-studied patient population that have only achieved modest survival gains compared to other groups. We present our institutional experience of AYA with sarcoma who underwent comprehensive molecular profiling (CMP) using either large-panel targeted DNA sequencing or whole genome and transcriptome sequencing and evaluated the feasibility and clinical impact of this approach. Genomic variants detected were determined to be clinically relevant and actionable following the Molecular Tumour Board evaluation. Clinicians provided feedback regarding the utility of testing three months after reporting. Twenty-five patients who were recruited for CMP are included in this analysis. The median time from consent to final molecular report was 45 days (interquartile range 37-57). Potentially actionable variants were detected for 14 patients (56%) and new treatment recommendations were identified for 12 patients (48%). Pathogenic germline variants were identified in three patients (12%), and one patient had a change of diagnosis. Implementation for CMP for AYA with sarcoma is clinically valuable, feasible and should be increasingly integrated into routine clinical practice as technologies and turnaround times continue to improve.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Background: Despite their generally favorable prognosis, hepatic fibrosis remains a possible complication for hepatitis B virus (HBV) inactive carriers. This study aimed to estimate the prevalence of significant fibrosis and associated risk factors among Omani HBV inactive carriers. Methods: A retrospective study was conducted of 200 Omani HBV inactive carriers visiting a tertiary hospital in Muscat, Oman, between January 2017 and December 2018. Significant fibrosis (stage F2 or higher) was identified using two-dimensional shear-wave elastography. Baseline clinical, laboratory, and radiological data were analyzed to determine associations. Results: Of the total sample, 106 patients (53%) were male, and the mean age was 44.6 ± 9.3 years. The prevalence of significant fibrosis was 20% (n = 40). Male gender (p = 0.007), age ≥60 years (p = 0.024), and fatty changes in liver ultrasound (p = 0.044) were found to be independent factors for significant fibrosis. Conclusion: the prevalence of significant fibrosis was relatively high among a sample of Omani HBV inactive carriers, with several sociodemographic and clinical risk factors identified. Periodic assessment of liver function is needed for patients with these risk factors; moreover, routine biochemical parameters could be useful predictors of disease prognosis. Further research is recommended to substantiate these findings.

Object. Utilization of pedicle screws (PS) for spine stabilization is common in spinal surgery. With reliance on visual inspection of anatomical landmarks prior to screw placement, the free-hand technique requires a high level of surgeon skill and precision. Three-dimensional (3D) computer-assisted virtual neuronavigation improves the precision of PS placement and minimize steps. Methods. Twenty-three patients with degenerative, traumatic, or neoplastic pathologies received treatment via a novel three-step PS technique that utilizes a navigated power driver in combination with virtual screw technology. 1) Following visualization of neuroanatomy using intraoperative CT, a navigated 3-mm match stick drill bit was inserted at anatomical entry point with screen projection showing virtual screw. 2) Navigated Stryker Cordless Driver with appropriate tap was used to access vertebral body through pedicle with screen projection again showing virtual screw. 3) Navigated Stryker Cordless Driver with actual screw was used with screen projection showing the same virtual screw. One hundred and forty-four consecutive screws were inserted using this three-step, navigated driver, virtual screw technique. Results. Only 1 screw needed intraoperative revision after insertion using the three-step, navigated driver, virtual PS technique. This amounts to a 0.69% revision rate. One hundred percent of patients had intraoperative CT reconstructed images to confirm hardware placement. Conclusions. Pedicle screw placement utilizing the Stryker-Ziehm neuronavigation virtual screw technology with a three step, navigated power drill technique is safe and effective.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Habit theory suggests that behavior performed in the presence of consistent cues is a core ingredient for successful habit development, with the repeated presence of these consistent cues facilitating the activation of automatic responses in future. We tested this assumption in a sample of 68 undergraduate students who, at baseline, reported on their physical activity behavior over the past year then, two weeks later, responded to measures of cue consistency, habit, and physical activity performance over the previous two weeks. As expected, habit mediated the effects of past behavior on prospectively measured behavior. Moreover, the mediating effect of habit between past and future behavior was significantly stronger in those reporting undertaking physical activity at the same time of day, doing the same activity, and in the same mood. Consistent place, people, and part of routine did not moderate the effects of habit. Results provide formative evidence for a key assertion of habit theory, that consistent contextual and internal cues are a cornerstone of habitual development and action, but also indicate the importance of examining different forms of cues and their impact on the formation and enaction of habits as some cues over others may be more relevant.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

The biogeography of inflammation in ulcerative colitis (UC) suggests a proximal to distal concentration gradient of a toxin. Hydrogen sulfide (H2S) has long been considered one such toxin candidate, and dietary sulfur along with the abundance of sulfate reducing bacteria (SRB) were considered the primary determinants of H2S production and clinical course of UC. The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and SRB abundance. Here we present an updated formulation of the H2S toxin hypothesis for UC pathogenesis, which strives to incorporate the interdependency of diet composition and the metabolic activity of the entire colon microbial community. Specifically, we suggest that the increasing severity of inflammation along the proximal-to-distal axis in UC is due to dilution of beneficial factors, concentration of toxic factors, and changing detoxification capacity of the host, all of which are intimately linked to the nutrient flow from the diet.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

The main motive of this study was to find an auxiliary application of the discarded agricultural remnants and poultry waste. Rice straw and chicken feathers are disposed off as landfills or incinerated causing pollution and environmental threats after their primary consumption. In this study epoxy composites were made using varying proportions of these raw and alkali treated materials. Flexural strength of the composites decreased till 35% fiber loading, followed by an increase. Chicken feather composites showed increased impact strength with fiber addition. Alkali treatment improved the mechanical properties of rice straw composites. Alkali treated chicken feather composites showed better impact strength but no significant change in flexural strength. Hybrid composites explicated enhanced properties both before and after alkali treatment corroborating noteworthy interfacial adhesion and synergistic effect of these fibers as ascertained from SEM images. The study evinced a better option for averting environmental problems by recycling these disposed materials.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

The Ionian Sea is a crucial intersection for various water masses in the Mediterranean. Its hydrography and dynamics play a significant role in the seawater budgets and biogeochemistry of the neighboring sub-basins. Multiple theories have been formulated to gain a better understanding of the Ionian dynamics. These theories primarily attribute the variability of the near-surface Ionian circulation to internal processes. Here, we utilize horizontal currents and temperature-salinity profiles from the Copernicus reanalysis to examine the contribution of baroclinic modes to the variability of the basin horizontal circulation. Our findings demonstrate that, although the basin vertical structure is characterized by three layers, the primary patterns of the Ionian circulation can be attributed to the first baroclinic mode. This mode, along with the barotropic mode, accounts for over 85% of the overall variability in the Ionian circulation, suggesting that only one of the three interfaces separating the different water masses in the basin is dynamically active. We estimate the depth of this interface to be about 490 m. Additionally, our analysis shows that more than 90% of the kinetic energy over the water column is localized above this interface, indicating that the deep layer of the Ionian is dynamically nearly inert.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

This study describes the seasonal course of denitrifying and nitrate reducing bacteria in a dimictic mesotrophic lake (Lake Scharmützelsee, Brandenburg, Germany) within a three-year period from 2011 to 2013. The bacterial cell numbers were quantified by fluorescence microscopy, most probable number (MPN) and PCR dependent quantification of the chromosomal 16S rDNA and of the nirS and nirK gene copy number. The highest seasonal differences (up to three orders of magnitudes) has been measured by MPN in the epilimnion. This variation was not reflected by PCR dependent approaches or direct microscopical enumeration. At adverse conditions (low temperature and/or low nitrate concentrations), the differences between MPN and gene copy numbers increased up to five orders of magnitudes and decreased to one magnitude at favorable environmental conditions. These results can be explained best by an increasing ratio of viable but not cultivable (VBNC) cells or dead cells at impairing conditions. In the hypolimnion, the courses of MPN and nir gene copy numbers were similar. This can be explained by higher feeding pressure and therefore smaller amounts of dormant cells. In the pelagial in general, the total cell numbers enumerated by either microscopical or molecular approaches were similar. In the sediment, more than 99 % of the DNA was obviously not related to viable bacteria but was rather “dead DNA” in dead cells or adsorbed to particle surfaces.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

The review scrutinizes the currently performed research on the new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifers of bitumen. It investigates innovative methods, including using waste polymers as modifiers, and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, the review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

Today, the kennel is considered one of the crucial concerns of the human-animal relationship, since it is very often regarded as animal dump where dogs exile, thus representing a burden on society. Therefore, drawing up strategies for a new “kennel conception”, as an added value for human society, environment, and dogs is still an unmet need. Here, we described the activities of a shelter dog in southern Italy, which faithfully meets criteria aimed at One Health perspective. It normally relies on an initial careful assessment by veterinary behaviorist, in order to guarantee the most suitable life conditions for the animals in the kennels, increase the chances of adoption and enroll them in projects tailored to their predispositions. Accordingly, dogs housed there are normally included in training courses to increase the skills to be used in different human social contexts, like support to the inmates, rescue in the rubble, animal-assisted interventions, as well as zooanthropology educational programs. The main strength for this groundbreaking shelter relies on the environmental protection schedule, where the purposes, employing technically and economically sustainable tools, point towards the continuous improvement and minimization of the environmental impact, promoting joint integrative projects for a sustainable One Health framework.

In this work, an innovative numerical approach for polylinear approximation (polylinearization) of non-self-intersecting compact sensor characteristics (transfer functions) specified either pointwise or analytically is introduced. The goal is to optimally partition the sensor characteristic, i.e. to select the vertices of the approximating polyline (approximant) along with their positions on, the sensor characteristics so that the distance (i.e. the separation) between the approximant and the characteristic is rendered below a certain problem-specific tolerance. To achieve this goal, two alternative non-linear optimization problems are solved, whose essential difference is in the adopted quantitative measure of the separation between the transfer function and the approximant. In the first problem, which relates to absolutely integrable sensor characteristics (their energy is not necessarily finite, but they can be represented in terms of convergent Fourier series), the polylinearization is constructed by numerical minimization of the L^1--metric (a distance-based separation measure), concerning the number of polyline vertices and their locations. In the second problem which covers the quadratically integrable sensor characteristics (whose energy is finite, but they do not necessarily admit a representation in terms of convergent Fourier series), the polylinearization is constructed by minimizing numerically the L^2-metric (area-, or energy-based separation measure) for the same set of optimization variables –the locations, and the number of polyline vertices.

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.

Biochar is a carbonaceous material derived from the thermochemical conversion of biomass under oxygen-lean conditions. Its properties render it many applications in agriculture, environmental remediation, and catalysis. Commonly produced by pyrolysis under a nitrogen atmosphere, the biochar composition is influenced mainly by residence time, heating rate, and process temperature. The existing literature primarily assesses biochar properties, such as ultimate, proximate, calorific, porosity, and combustibility, generated under various thermo-conversion conditions. However, there is a notable lack of sufficient investigation and attention given to the practical application of biochar. This article seeks to bridge that gap by enhancing the comprehension of the necessary experimental assessment for specific biochar applications and proposing process optimization methods using Multi-Criteria Decision Analysis (MCDA). By delving into these aspects, the study offers a concise overview of biochar production and presents a comprehensive panorama based on articles and patents. Additionally, the research explores the physicochemical characterization techniques associated with biochar and its various applications in conjunction with MCDA. This comprehensive approach aims to uncover valuable insights that could further advance the practical and sustainable utilization of biochar in a wide range of fields.

We have now identified two thermodynamically distinct types (A and B) of energetic processes naturally occurring on Earth. Type A energy processes such as the classical heat engines, apparently well follow the second law of thermodynamics; Type B energy processes, such as the newly discovered thermotrophic function that isothermally utilizes environmental heat energy to do useful work in driving ATP synthesis, which follows the first law of thermodynamics (conservation of mass and energy) but does not have to be constrained by the second law, owing to their special asymmetric functions. Several Type-B energy processes such as asymmetric-function-gated isothermal electricity and epicatalysis have been created through human efforts. The innovative efforts on Type-B processes to enable isothermally utilizing endless environmental heat energy could help to liberate all peoples from their dependence on fossil fuel energy, thus helping to reduce greenhouse gas CO2 emissions and control climate change towards a sustainable future for the humanity on Earth.

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) were susceptible to HBV, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.

In late December 2019 a novel RNA beta-coronavirus was recognized as the causative agent of previously pneumonia cases of unknown origin. The virus was successively named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) as well as the respiratory illness that it causes Coronavirus disease 19 (COVID-19) (1, 2). The global spread of SARS-CoV-2 and the thousands of deaths caused by COVID-19 led the World Health Organization (WHO) to declare a pandemic on 11 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. Indeed, even if most patients with COVID-19 are asymptomatic or experience mild self-limiting disease, 14% of them progress to severe disease and 5% to critical illness with complications, such as interstitial pneumonia, respiratory failure with acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndromes (MODS) (3). It is accepted that SARS-CoV-2 primarily affects the respiratory system, although other organs are also involved (4). The virus enters host cells by attaching its Spike like surface projections to the angiotensin-converting enzyme-2 (ACE2) receptor which is mainly expressed on alveolar epithelial cells and in nearly all human organs in varying degrees. Thus, although the central target of SARS-CoV-2 infection is the lung, the wide distribution of ACE2 receptors in other organs may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damages that have to be closely monitored during the disease (5, 6). The virus then activates the innate and adaptive immune system resulting in a large number of cytokines release, known as “cytokine storm”, that is directly correlated with tissue injury and unfavourable prognosis of severe lung disease (7). In particular, interleukin (IL)-6 seems to plays an important role in driving this cytokine release so that its increased levels have been recognized as a hallmark inflammatory signature in sera of COVID-19 patients (8). IL-6 is a polyfunctional cytokine with both anti-inflammatory and pro-inflammatory properties which exerts its several functions through two main signal transduction pathways (9). In the classical signal transduction pathway, IL-6 binds to IL-6-trans membrane receptor (IL-6R) to form a complex that, then, binds to the trans membrane glycoprotein gp130, inducing its homo-dimerization and initiating intracellular signal transduction. This kind of signaling is limited to cells (hepatocytes, macrophages, neutrophils, T cells, etc.) that express IL-6R on their cell surface (10). Nevertheless, cells do not express IL- 6R, as stromal and epithelial cells, are able to still respond to IL-6 because the soluble form of the receptor (sIL-6R) binds to IL-6 in circle and then anchors to membrane gp130 receptor, initiating the trans-signaling pathway. For this reason, sIL-6R is able to increase the function of IL-6 and is considered the agonist form of its receptor. When the level of IL-6 increases, its effects are widely expressed because gp130 molecules are ubiquitous and, therefore, also present in cells without IL-6R in the membrane form. On the contrary, a soluble form of the glycoprotein 130 (sgp130) can complex with sIL-6R to prevent the sIL-6R from binding to the membrane-bound gp130. In this case sgp130 is able to decrease the function of IL-6 and is considered the antagonist form of IL-6 receptor system (11). Based on the central role of IL-6 in the inflammatory pathology of COVID-19 and the consistent association between elevated levels of the cytokine and severe disease outcomes found in the first phase of infection, we sought to analysis IL-6 and its soluble receptor complex behavior during the different waves of COVID-19 pandemic, in order to evaluate the possible differences which occur among them and to hypothesize if they might be used as prognostic markers of disease severity.

Backyard production systems (BPS) are highly distributed in central Chile. Poultry BPS have been previously characterized; however, swine BPS have not yet been deeply characterized in central Chile. In addition, there is evidence that zoonotic pathogens, such as influenza A virus and Salmonella spp., are circulating in both poultry and pigs kept these production systems. A total of 358 BPS located in central Chile were evaluated between 2013 and 2015 by interviewing farm owners. Severe deficiencies in biosecurity measures were observed. The value chain of swine backyard production identified feeding, products and veterinary visits, and replacement or breeding animals as the main inputs to the backyard. The most common origin of swine replacements was from outside the BPS (63%). Meat and live animals (piglets and breeding animals) were identified as the main outputs of the system. In 16% of BPS, breeding animals were lent to other BPS, indicating the existence of animal and animal products movement in and out of backyard farms. Results from this study suggest that swine BPS in central Chile represent an animal-human interphase that need special attention to direct preventive measures aimed at avoiding the introduction and dissemination of animal pathogens and the emergence of zoonotic pathogens.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia caused by both immune-mediated platelet destruction and impaired platelet production in the bone mar-row, in the absence of any other identifiable cause of low platelets count. ITP in adult patients is a disease that frequently relapses and/or becomes refractory to multiple treatments during its course, with only a small minority of adult patients attaining a sustained complete remission off-therapy. Treatment of refrac-tory ITP can be challenging, due to the unlikeliness of attaining complete response over time. On the other hand, isolated thrombocytopenia may be due to a misdiagnosed clonal myeloid disorder, such as myelodys-plastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), thus mimicking ITP. We here per-form a narrative review on the association between ITP and MDS/CMML and the possibility of overlap and misdiagnosis between these conditions, while we report also the case a patient treated for a severe re-fractory thrombocytopenia which bone marrow examination led to suspect an overlap of MDS and ITP. Our clinical case describes ITP which is refractory to glucocorticoids, high-dose immunoglobulins, Rituxi-mab, splenectomy, thrombopoietin receptor agonists and Fostamatinib, that ultimately attained a short-lived response to a hypometylating agent that was initiated due to bone marrow examination that aroused the suspect of MDS.

Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.

Maintaining the judiciary's power requires a high level of budgetary expenditure, but the specifics of this relationship have yet to be fully explored. Although several studies have analyzed the impact of spending in the judiciary through productivity and performance-related measures, none have employed machine learning techniques. This study examines the productivity of the judiciary based on spending and other variables using machine learning techniques, including clustering and neural networks. The final neural network model supports the results of Pearson's parametric correlation test, which found no significant correlation between expenditure and productivity. This study's findings demonstrate the importance of understanding that increased public budgetary expenditure alone is insufficient for improving the judiciary's efficiency. Instead, other administrative and technical measures are necessary to meet the demands of the Brazilian judiciary and improve service delivery rates. These findings offer important theoretical and managerial contributions to the field.

Feral cats are both difficult to manage and harder to monitor. We analysed the cost-efficacy of monitoring the pre- and post-bait abundance of feral cats via camera-traps or track counts using four years of data from the Matuwa Indigenous protected Area. Additionally, we report on the recovery of the feral cat population and the efficacy of subsequent Eradicat® aerial baiting programs following 12 months of intensive feral cat control in 2019 that consisted of aerial baiting and leg-hold trapping. Significantly fewer cats were captured in 2020 (n = 8) compared to 2019 (n = 126). Pre-baiting surveys for 2020 and 2021 suggested that the population of feral cats on Matuwa was very low, at 5.5 and 4.4 cats/100 km respectively, which is well below our target threshold of 10 cats/100 km. Post-baiting surveys then recorded 3.6 and 3.0 cats/100 km respectively, which still equates to a 35% and 32% reduction in cat activity. Track counts recorded significantly more feral cats than camera traps and were cheaper to implement. We recommend that at least two methods of monitoring cats be implemented to prevent erroneous conclusions.

In this paper we develop and explore a methodical pipeline for swimmer localisation in outdoor environments. The developed framework is intended to be used for enhancing swimmer safety. A main issue we deal with by the proposed approach is the lack of real world training data in such outdoor environments. Natural lighting changes, dynamic water textures and possibly barely visible swimming persons are key elements to approach. We account for these difficulties by adopting an effective background removal technique with available training data. This allows us to edit swimmers into natural environment backgrounds for the use in subsequent image augmentation. We created 17 training datasets with real images, synthetic images and a mixture of both to investigate different aspects and characteristics of the proposed approach. The datasets are used to train a YOLO architecture for the possible future application in real-time detection. The trained framework is then tested and evaluated on outdoor environment imagery acquired by a safety drone to investigate and confirm the usefulness for outdoor swimmer localisation.

Selective Paste Intrusion (SPI) is an additive manufacturing (AM) process in which thin layers of aggregates are selectively bonded by cement paste only where the structure is to be produced. In this way, concrete elements with complex geometries and structures can be created. Reinforcement is required to increase the flexural strength of the concrete elements and, thus, enable their applicability in practice. Integrating the reinforcement is a difficult task, particularly in the case of SPI due to the layer-wise printing method. Especially with respect to possible complex structures, the production of the reinforcement needs to be adapted to SPI, thereby offering a high degree of freedom. One concept for a reinforcement integration is combining the two additive manufacturing processes SPI and Wire and Arc Additive Manufacturing (WAAM). However, since the two processes serve different fields of application, their compatibility is not necessarily given. Ongoing investigations show that the temperatures caused by WAAM adversely affect both, the cement paste rheology required for sufficient paste penetration into the particle bed and the overall concrete strength. This paper provides an overview of ongoing research focusing on different cooling strategies and their effects on the compressive strength of SPI-printed concrete parts.

Biochar application to soil has been proposed as a means for reducing soil greenhouse gas emissions and mitigating climate change. The effects, however, of interactions between biochar, moisture and temperature on soil CO₂ and N₂O emissions, remain poorly understood. Furthermore, the applicability of lab-scale observations to field conditions in diverse agroecosystems remains uncertain. Here we investigate the impact of a mixed wood gasification biochar on CO₂ and N₂O emissions from loess-derived soils using: (1) controlled laboratory incubations at three moisture (27, 31 and 35%) and three temperature (10, 20 and 30°C) levels, and (2) a field study with four cropping systems (continuous corn, switchgrass, low diversity grass mix, and high diversity grass-forb mix). Biochar reduced N₂O emissions under specific temperatures and moistures in the laboratory and in the continuous corn cropping system in the field. However, the effect of biochar on N₂O emissions was only significant in the field, and no effect on cumulative CO₂ emissions was observed. Cropping system also had a significant effect in the field study, with soils in grass and grass-forb cropping systems emitting more CO₂ and less N₂O than corn cropping systems. Observed biochar effects were consistent with previous studies showing that biochar amendments can reduce soil N₂O emissions under specific, but not all, conditions. The disparity in N₂O emission responses at the lab and field scales suggests that laboratory incubation experiments are not reliable for predicting the impact of biochar at the field scale.

Soil amendments with composted organic materials are recommended to increase soil organic matter (SOM), promote soil fertility, and the Circular Economy. Growing areas of hedged olive groves in southern Iberia peninsula generate huge amounts of olive leaves whose potential as soil organic amendment is not fully studied. An experimental field trial in a hedged olive grove (cv. “Cobrançosa”) was set up near Portalegre, Portugal, to test a compost of olive leaves plus sheep manure (2:1) applied in the row, at soil surface. Three nominal rates (0 or control, 2.5 and 5.0 kg m-2) were used, in a complete randomized block setup (3 treatments, 3 replicas, 9 plots) and soil chemical properties of layers 0-5, 5-15, and 15-30 cm deep were annually monitored. Results (mainly in layer 0-5 cm) showed increases in total N, carbon of the particulate organic matter (POM-C), permanganate oxidizable carbon (POX-C), extractable phosphorus, and zinc, after one year, and increases in soil organic carbon (SOC), C-stock, pHKCl, extractable phosphorus, and zinc, after two years. POX-C was the most sensitive SOM-related indicator, showing increases up to 30 cm deep after one year. This compost improved soil fertility, but should be monitored over longer periods of time, namely for SOC and extractable zinc content.

Rhes is one of the most interesting proteins regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. It is expressed at high levels in the dorsal striatum, with a medial-to-lateral expression gradient reflecting that of both dopamine D2 and adenosine A2A receptors. Rhes is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with Rhes-dependent regulation of dopaminergic transmission, several data showed that lack of Rhes enhanced cocaine and amphetamine-induced motor stimulation in mice. Previous studies showed that pharmacological depletion of dopamine significantly reduces Rhes mRNA levels in rodents, non-human primates and Parkinson’s disease (PD) patients, suggesting a link between dopaminergic innervation and physiological Rhes mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L-DOPA-induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes-dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system.

Increased proliferation of IT services in all sectors has reinforced the adoption and diffusion across all levels of education and training institutions. However, lack of awareness of and knowledge about the key challenges and opportunities of elearning, seem to allude policymakers, resulting in low adoption or increased failure rate of many e-learning projects. Our study tries to address this problem through a review of relevant literature in e-learning. Our goal was to draw from the existing literature, insights into the opportunities and challenges of e-learning diffusion, and the current state-of-research in the field. To do this, we employed a systematic review of literature on some of the salient opportunities and challenges of e-learning innovation for educational institutions. These results aimed to inform policymakers and suggest some interesting issues to advance the research and adoption and diffusion of e-learning. Moreover, the bibliometric analysis shows that the field is experiencing high research attraction among scholars. However, several research areas in the field witnessed relatively low research paucity. Based on these findings, we discussed topics for possible future research.

Image recovery by dictionary learning is of potential interest for many possible applications. To learn a dictionary, one needs to solve a minimization problem where the solution should be sparse. The K-SVD formalism, which is a generalization of the K-means algorithm, is one of the most popular methods to achieve this aim. We explain the preprocessing that is needed to bring images into a manageable format for the optimization problem.The learning process then takes place in terms of solving for sparse representations of the image batches. The main contribution of this paper is to give an experimental analysis of the recovery for highly textured imagery. For our study, we employ a subset of the Brodatz database. We show that the recovery of sharp edges plays a considerable role. Additionally, we study the effects of varying the number dictionary elements for that purpose.

Quantum logic is a well-structured theory, which has recently received some attention because of its fundamental relation to quantum computing. However, the complex foundation of quantum logic borrowing concepts from different branches of mathematics as well as its peculiar settings have made it a non-trivial task to device suitable applications. This article aims to propose for the first time an approach to use quantum logic in image processing at hand of a process for shape classification. We show how to make use of the principal component analysis to realize quantum logical propositions. In this way we are able to assign a concrete meaning to the rather abstract quantum logical concepts, and we are able to compute a probability measure from the principal components. For shape classification we consider encrypting given point clouds of different objects by making use of specific distance histograms. This enables to initiate the principal component analysis. At hand of experiments, we explore the possibility to distinguish between different geometrical objects and discuss the results in terms of quantum logical interpretation.

The conventional explanation of delayed-choice experiments seems to violate our causal intuition. This apparent violation is caused by a misinterpretation of the conventional formulation of quantum mechanics. I reanalyze these experiments using advanced and time-symmetric formulations of quantum mechanics. All three formulations give the same experimental predictions, but the advanced and time-symmetric formulations violate our causal intuition that effects only happen after causes. I explore reasons why our causal intuition may be wrong at the quantum level. I also suggest how conventional causation might be recovered in the classical limit, and speculate on cosmological boundary conditions.

226Ra and 228Ra are typically monitored for groundwater and surface water compliance at legacy U mining and milling sites. Groundwater monitoring results for combined Ra (226Ra+228Ra) reported by the existing contract laboratory at a former U mine and mill Site (Wyoming, USA) have been highly variable and with increasing trends at the Site compliance and background wells since the method was changed in 2005. Sample reanalysis has indicated poor reproducibility and significant analytical error in 228Ra measurements. An interlaboratory comparison was conducted to evaluate the potential causes of the high variability and analytical error. Two different methods were used for 226Ra (M903.0 and M903.1) and 228Ra (M904.0 and Ra-05). 226Ra results were less variable compared to 228Ra, and 228Ra data from the existing laboratory were qualified as estimated with high bias due to detection of 228Ra in the field blank. Compliance with the 226Ra+228Ra groundwater standard was either met or not met, depending on which laboratory conducted the analyses. Specific laboratory techniques, rather than the analytical method, are contributing to elevated 228Ra values being reported. It was recommended that samples whose 226Ra+228Ra results exceed the Site standard in the future be reanalyzed by the existing laboratory with a sample split also being sent to an outside laboratory for confirmatory analysis.

Given the remarkable progress in global health and overall quality of life, the significant rise in life expectancy has become intertwined with the surging occurrence of neurodegenerative disorders (ND). This emerging trend is poised to pose a substantial challenge to the fields of medicine and public health in the years ahead. In this context, Alzheimer's disease (AD) is regarded as a ND that causes recent memory loss, motor impairment and cognitive deficits. AD is the most common cause of dementia in the elderly and its development is linked to multifactorial interac-tions between the environment, genetics, aging and lifestyle. The pathological hallmarks in AD are the accumulation of beta amyloid (A) peptide, the hyperphosphorylation of tau protein, neuro-toxic events and impaired glucose metabolism. Due to pharmacological limitations and in view of the prevailing glycemic hypometabolism, the ketogenic diet (KD) emerges as a promising non-pharmacological possibility for managing AD, an approach that has already demonstrated efficacy in addressing other disorders, notably epilepsy. KD consists of a food regimen in which carbohydrate intake is discouraged at the expense of increased lipid consumption, inducing met-abolic ketosis, whereby the main source of energy becomes ketone bodies, instead of glucose. Thus, under these dietary conditions, neuronal death through lack of energy would be decreased, inasmuch as the metabolism of lipids is not impaired in AD. In this way, the clinical picture of patients with AD would potentially improve, through the slowing down of symptoms and delaying the progression of the disease. Hence, this review aims to explore the rationale behind utilizing the KD in AD treatment while emphasizing the metabolic interplay between KD and the improvement of AD indicators, drawing insights from both pre-clinical and clinical investigations.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

California and most other coastlines around the world are being impacted by both long-term sea-level rise and short-term extreme events. Because of California’s long and intensively developed coastline, it is an important area for evaluating responses to these challenges. The predominant historic approach to coastal erosion in California and globally has been the construction of hard coastal armoring such as seawalls and rock revetments. The concept of living shorelines – defined as using natural elements like plants, sand or rocks to stabilize the coastline – has been widely proposed as a soft or green response to coastal erosion and flooding. These approaches have very limited application in high-energy environments, however, such as California’s 1,100-mile-long outer coast and are not realistic solutions for protection from wave attack at high tides or long-term sea-level rise. Each of the state’s coastal communities need to identify their most vulnerable areas, develop adaptation plans, and plan eventual relocation strategies in response to an accelerating sea-level rise.

The large-scale processing of Cassava (Manihot esculenta Crantz.) generates significant quantities of solid wastes annually. Cassava peels (CP) account for 5 wt.% - 30 wt.% of wastes from the processing of cassava tubers. The poor disposal and management of CP pose risks to human health, safety and the environment. Therefore, there is an urgent need to identify and examine low cost, socially acceptable and environmentally friendly strategies to mitigate the immediate and long terms disposal and management challenges. Lack of such measures results in the accumulation of CP wastes, which are currently buried, combusted, or dumped in open fields. Therefore, this paper reviewed the potential routes for the biochemical, thermochemical, and plasma valorisation of CP. The literature reviewed revealed that biochemical technologies such as anaerobic digestion (AD) and fermentation are the most widely utilised approaches currently adopted for CP valorisation. AD produces biogas (methane 50-72 vol. % and carbon dioxide 25-45 vol. %), whereas fermentation yields bioethanol. However, the numerous challenges such as substrate-induced inhibition, associated with the biochemical processes hamper microbial degradation, methane formation, and process efficiency. Furthermore, the processes generate secondary wastes or digestate/sludge, which requires additional processing before disposal. Therefore, innovative thermal, thermochemical, and plasma technologies were proposed to valorise CP into syngas, biofuels, bioenergy, biochemicals, and fertilizers, among others. However, the waste products of fermentation cannot be effectively utilised as bio-fertilizers, whereas bioethanol causes corrosion in engines. Overall, the biochemical, thermal, thermochemical and plasma technologies can effectively valorise CP for effective net energy generation.

This study presents a preliminary analysis of the chemical and thermal fuel properties of Afuze (AFZ) coal extracted from coalfields in Owan East Local Government Area of Edo State, Nigeria. The chemical properties of AFZ were examined by combined scanning electron microscopy-energy dispersive X-ray (EDX), whereas the thermal properties were deduced by thermogravimetric analysis (TGA) under flash (50 °C/min heating rate) oxidative (combustion) and non-oxidative (pyrolysis) conditions. The microstructure and morphology analysis of AFZ revealed has a compact structure comprising small-to-large, irregular shaped and exfoliated grains with a vitreous appearance typically ascribed to metal elements (Ti and Fe) kaolinite, quartz, and other clay minerals. Chemical analysis revealed carbon, oxygen, aluminium, silicon, sulphur, calcium, titanium, and iron in major and minor (trace) quantities. Thermal analysis under oxidative and non-oxidative conditions revealed degradation occurs in three stages, namely; drying or demineralisation, devolatilization or maceral degradation and the formation of char/coke or ash. Lastly, the findings showed that the temperature range for the oxidative thermal degradation process (338.58 - 756.76 °C) was higher than the non-oxidative process (378.43 - 615.34 °C). This observation can be explained by the exothermic nature of the oxidative (combustion) process, which ensures greater heat supply required to thermally soften or degrade the maceral coal components. Overall, the oxidative process yielded the residual mass (RM = 21.97%) and mass loss (ML = 78.03%). The lower ML (49.03%) but higher RM (50.97%) observed during non-oxidative degradation of AFZ could be ascribed to the largely endothermic nature of the process.

Although the phenomenon of serial killers has received great attention from media, governments, and public, very little information is known about them and very few theories are presented by researchers specifically their definition and motives for killing. Through cross tabulation analysis of top ninety-eight serial killers, this present study poses six questions that investigate the correlations between, offender's gender, offender's level of education, time span of killing, killing severity, number of victims, killer's type of abuse, motives for killing, and victim's profile. Findings show that males kill more than females and for longer time, less educated serial killers kill more horribly, female serial killers consider their family members easy target, and finally males kill most for enjoyment and sex and females kill for financial gains.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

COVID-19 was an inflammatory pneumonia caused by a respiratory infection with a coronavirus named SARS-CoV-2. Severely ill COVID-19 patients could die of acute pulmonary and systemic inflammation. Thus, there was a theory that long COVID-19 shared many similarities with systemic autoimmune diseases. There was also a theory that the SARS-CoV-2 virus could infect many cell- and tissue-types distributed throughout multiple organ systems of the body. I aim to review the above theories using unbiased high-throughput datasets cataloguing gene expression. Studies reviewed used the technology of next generation sequencing, either as bulk tissue RNA sequencing, or as single-cell RNAs sequencing; ingenious methods for signal deconvolution were then used to identify individual cell types. Datasets reviewed suggested that severe COVID-19 induced expression of genes associated with pro-inflammatory signaling, tissue development or remodeling, scarring, or cell death. The datasets also provided evidence for several inflammatory syndromes associated with COVID-19, such as neuronal COVID, acute respiratory disease syndrome, vascular inflammation, or multisystem inflammatory syndrome. Indeed, inflammatory signal during severe COVID-19 was reported in many cell types, for example in structural cells, in infiltrating immune cells, in the vascular system, or in circulating cells in the blood. There was also frequently a change in proportions of immune cell-types in the blood, epithelial cells in the lungs, or among infiltrating immune cells.

This article presents a critical review of the current and future state of “business architecture” within the enterprise architecture frameworks. The review is conducted in the following four stages. In the first stage of analysis, the research and publication questions are established. In the second stage, the search for information is designed and implemented using the Prisma methodology, and once the selection criteria were applied, 75 article-type documents were selected from Scopus, WoS, and Dimensions databases. In the third stage, the information analysis is conducted, and then it is synthesized. Finally, in fourth stage, the discussion is elaborated. This research contributes in understanding the current and future trends of business architecture in Industry 4.0. Considering the challenges of the changing market, the results show the need to implement architectures and dynamic business models, including their artifacts, in a globalized context immersed in new technologies.

Considerable efforts have been devoted to modifying gravity, which aim to elucidate the possible existence or nature of dark matter and energy, describe observational data more effectively, and formulate quantum gravity. In addition, despite the immense success of the quantum field theory, the framework requires renormalization techniques and breaks down at high energies. Recently, the Planck legacy 2018 release has confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This study considers the implied curvature of the early Universe as the curvature of “the background or 4D conformal bulk as a manifestation of vacuum energy” and distinguishes it from the localized curvature that is induced in the bulk by the presence of celestial objects that are regarded as ”4D relativistic cloud-worlds.” Analogously, because gravity appears to emerge owing to spacetime curvature and does not exhibit critical characteristics shared by other fields, it has been incorporated as the local curvature of the bulk affecting the embedded quantum fields that are regarded as propagating “4D relativistic quantum clouds.” To consider the effects of the bulk on embedded clouds, this paper presents interaction field equations in terms of brane-world modified gravity and the perspective of geometrization of the quantum mechanics wherein gravity is manifested by the curvature of 4D conformal bulk as an indicator of the field strength of vacuum energy on the embedded 4D relativistic clouds in addition to the boundary interactions, which could remove the singularities and satisfy a conformal invariance theory. A visualization of the evolution of the 4D relativistic cloud-worlds over the conformal spacetime of the 4D bulk is presented, whereas the standard said theories can be recovered from the interaction field equations.

The adoption of ADS-B in Latin America has been gradual but steady. Some countries, such as Brazil, Chile and Mexico, have made significant progress in the implementation of this system, while others are still in the early stages. It should be noted that the implementation of ADS-B is used in both military and civilian environments. For this reason, this research aims to provide information on the different characteristics that make up the surveillance systems. However, there are fundamental factors to promote the adaptation of ADS-B in Latin America, since they reduce the risk of collisions and air accidents by providing accurate and real-time information on the position and altitude of aircraft. On the other hand, it allows optimizing flight routes and reducing waiting time on the ground, which translates into fuel and cost savings for airlines. ADS-B increases the number of aircraft that can safely operate in the same airspace, which is especially important in regions with growing air traffic. ADS-B adoption in Latin America is expected to continue to grow in the coming years. The drivers for ADS-B adoption remain in place, and governments in the region are taking steps to accelerate its implementation.

Neurological / neurovascular disorders constitute the leading cause of disability and second leading cause of deaths in the world. Some of the major neurological / neurovascular disorders or diseases include stroke, Alzheimer’s disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, etc. Their pathophysiology is considered as highly complex and has been blamed as the main obstacle in the development of any drugs for these diseases. In this review, we have described the endothelin system, their involvement in neurovascular disorders, importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN - sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders / diseases. We have highlighted the results of our pre-clinical and clinical studies related to these diseases. The phase I, safety and tolerability study of sovateltide has shown it as a highly safe and well tolerable compound at tested dosages, while pre-clinical and clinical phase II studies have demonstrated its efficacy in treating acute ischemic stroke, where it is currently being developed as a “First in Class” drug. Its testing in Alzheimer’s disease (AD), acute spinal cord injury and neonatal hypoxic-ischemic encephalopathy (HIE) is currently being carried out and are at different stages of drug development. Successful completion of these studies will prove the involvement of ETBRs signaling in neurological / neurovascular diseases and help in development of novel neurological drugs in future.

B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an “open chromatin” state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacks both GCN5 and PCAF in B cells. We found that double-deficient mice possess low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We conclude that both GCN5 and PCAF are required for B cell development in vivo.

Abstract: A large number of collecting expeditions were launched in regions of ‘centers of diversity’ and hundreds of thousands of sample have been collected and stored in gene banks as ‘genetic resources’. So far, only a small number of the samples have been evaluated for their biotic and abiotic stress tolerance. Now, their time to become useful has come. A new global phenomenon has arisen – climate change. The crop genetic resources and their wild progenitors that have survived countless years of changing environment during the last 11,000 years could harbor genes that may be useful under the new growing conditions and environmental factors thrown up by climate change and global warming. With the deployment of modern bio-engineering techniques selected genes or gene fragments can be transferred from genetic resources to modern varieties of crop plants to make them well-prepared to mitigate the effects of global warming and climate change. The latter is the most serious issue facing plant breeders today. New pests and diseases could affect crop production. These review paper discusses various impacts and issues as a result of this phenomenon and suggest ways to safeguard our most important crops through better management of crop plant genetic resources in the near future.

The recent Planck Legacy release confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background (CMB) power spectra, which endorses the positive curvature of the early Universe with a confidence level exceeding 99%. In this study, the pre-existing curvature is incorporated to extend the field equations where the derived wave function of the Universe is utilized to model Universe evolution with reference to the scale factor of the early Universe and its radius of curvature upon the emission of the CMB. The wave function reveals both positive and negative solutions, implying that matter and antimatter of early Universe plasma evolve in opposite directions as distinct Universe sides. The wave function indicates that a nascent hyperbolic expansion is followed by a first phase of decelerating expansion away from early plasma during the first 10 Gyr, and then, a second phase of accelerating expansion in reverse directions, whereby both Universe sides free-fall towards each other under gravitational acceleration. Simulations of the predicted conformal curvature evolution demonstrate the fast orbital speed of outer stars owing to the external fields exerted on galaxies as they travel through conformally curved space-time. Finally, the wave function predicts an eventual time-reversal phase comprising rapid spatial contraction that culminates in a Big Crunch, signalling a cyclic Universe. These findings reveal that early plasma could have separated and evolved into distinct sides that collectively and geometrically influencing the Universe evolution, physically explanting the effects attributed to dark matter and energy.

The shrimp industry in the Philippines play a vital role in the local and national economy through exports with markets abroad such as in South Korea, Japan, the USA, and others. This study aimed to describe the various cultural and operational characteristics of small-holder and commercial shrimp farms (P. vannamei) in the Davao region. It also evaluated the current risks and challenges faced by the shrimp farmers. A semi-structured questionnaire that focused on shrimp farmers, and operators in the region was used to collect data with N=41 farmers and operator. The results showed that respondents were engaged in small-holder farming activities which had an average yield of 10 tons/ha. On the other hand, the commercial farms that operate intensively had an average yield of 24 tons/ha. Most small-holder operators used electric generator machines to conduct aeration in their farms using paddlewheels and blowers. For the commercial farms, more paddlewheels and blowers were employed per pond compared to small-holder farms. Generally, the income of a farm was related to the yield of farms or the number of fries rather than social factors or size of farms cultivated. In terms of input costs, feeds were found to have the highest input costs, followed by the fry, fuel, labor, and others (fertilizers and water treatment chemicals). Most of the farmers mentioned that they are affected by diseases such as white spot syndrome (60%), black gills (35%), and red tail (5%). They perceived that the main contamination come from the water source (31%). The main threats mentioned are declining shrimp prices in the market, source of fry, water disposal, and overstocking, and water quality. Based on this study, farmers should follow good shrimp aquaculture practices and there is a need for them to regularly monitor their water quality.

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th Feb and 15th Feb. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a `delayed positive' test during isolation after initially testing negative, at least 7 days after last possible contact.

Abstract: Falls are among the top 10 causes of years lived with disability in people aged 75 and over. Preventive programs like case management (CM) are crucial. Objectives: To evaluate the effects of a multifactorial fall prevention program, based on CM, on physical performance, presence of pain and risk of falls and fractures in elderly people who have suffered falls. Methods: This is a randomized, single-blind clinical trial with parallel groups: intervention group (IG) and control group (CG) composed of 55 older people with a history of falls living in the community. All participants underwent an initial assessment via video call (containing anamnesis, Timed Up and Go test, Falls Risk Score, Short Physical Performance Battery and Clinical Frax). The IG underwent CM, the physical exercise protocol and the cognitive stimulation protocol. The CG was monitored through telephone calls and received general health and falls guidance. Results: No significant results were found in physical capacity, presence of pain, risk of falls and fractures between the intervention and control groups and between assessments. Conclusion: This program was not effective in improving functional performance, but it was important for characterizing pain and the probability of fracture in the next 10 years in this population.

The use of several light-related variables, such as the Secchi disc depth, the euphotic depth, and in particular, the diffuse attenuation coefficient (Kd), is deeply rooted in phytoplankton research, but these are not the most appropriate indicators of the amount of light available for photosynthesis. We argue that the variable of interest for phytoplankton is the mean light intensity in the mixed layer (Im), which represents the mean light to which phytoplankton cells are exposed throughout their life cycle, while being continuously mixed in the mixed layer. We use empirical data collected in different coastal ecosystems in southern Portugal to demonstrate why Im should be the preferred metric instead of the deeply rooted Kd. We show that, although the relationship between Im and Kd is inversely proportional, it is not always strong or even significant. Different Im values can be associated to the same Kd, but distinct Im have different physiological effects of phytoplankton. Therefore, Kd does not capture the amount of light available for photosynthesis, given that, unlike Im, Kd calculation does not consider the depth of the mixed layer. Therefore, we urge phytoplankton researchers to consider the measurement and calculation of Im when evaluating light-related processes in phytoplankton ecology.

Cladding is typically used to protect components from wear and corrosion while also improving the aesthetic value and reliability of the substrate. The cladding process induces significant residual stresses due to the temperature difference between the substrate and the clad layer. However, these residual stresses could be effectively utilized by modifying processes and geometrical parameters. This paper introduces a novel methodology for using the weld-cladding process as a cost-effective alternative to various existing reinforcement techniques. The numerical analyses are performed to maximize the reinforcement of a cylindrical tool. The investigation of how the weld cladding develops compressive stresses on the specimen in response to a change in the weld beads and the welding sequence is presented. For the benchmark shape, experimental verification of the numerical model is performed. The impact of the distance between the weld beads and the effect of the tool diameter is numerically investigated. Furthermore, the variation in compressive stresses due to temperature fluctuations during the extrusion process has been evaluated. The results showed that adequate compressive stresses are generated on the welded parts through the cladding process after cooling. Hence, the targeted reinforcement of the substrate can be achieved by optimizing the welding sequence and process parameters.

Brain is the most complex organ in the human body and it is divided into two hemispheres - left and right hemispheres. Left hemisphere is responsible for control of right side of our body whereas right hemisphere is responsible for control of left side of our body. Brain image segmentation from different neuroimaging modalities is one of the important parts in clinical diagnostic tools. Neuroimaging based digital imagery generally contain noise, inhomogeneity, aliasing artifacts, and orientational deviations. Therefore, accurate segmentation of brain images is a very difficult task. However, the development of accurate segmentation of brain images is very important and crucial for a correct diagnosis of any brain related diseases. One of the fundamental segmentation tasks is to identify and segment inter-hemispheric fissure/mid-sagittal plane, which separate the two hemispheres of the brain. Moreover, the symmetric/asymmetric analyses of left and right hemispheres of brain structures are important for radiologists to analyze diseases such as Alzheimer's, Autism, Schizophrenia, Lesions and Epilepsy. Therefore, in this paper we have analyzed the existing computational techniques used to find brain symmetric/asymmetric analysis in various neuroimaging techniques (MRI/CT/PET/SPECT), which are utilized for detecting various brain related disorders.

The Industrial Internet of Things (IIoT) paradigm is a key research area derived from the Internet of Things (IoT). The emergence of IIoT has enabled a revolution in manufacturing and production, through the employment of various embedded sensing devices connected with each other by an IoT network, along with a collection of enabling technologies such as artificial intelligence (AI) and edge/fog computing. One of the unrivaled characteristics of IIoT is the inter-connectivity provided to industries; however, this characteristic might open the door for cyber-criminals to launch various attacks. In fact, one of the major challenges hindering the prevalent adoption of the IIoT paradigm is IoT security. Inevitably, an increasing number of research proposals have been introduced over the last decade to overcome these security concerns. To obtain an overview of this research area, conducting a literature survey of the published research is necessary, eliciting the various security requirements and their considerations. This paper provides a literature survey of IIoT security, focused on the period from 2017 to 2023. We identify IIoT security threats and classify them into three categories, based on the IIoT layer they exploit to launch these attacks. Additionally, we characterize the security requirements that these attacks violate. Finally, we highlight how emerging technologies, such as AI and edge/fog computing, can be adopted to address security concerns and enhance IIoT security.

Anterior segment dysgenesis (ASD) encompasses a wide spectrum of developmental abnormalities of the anterior ocular segment, including congenital cataract, iris hypoplasia, aniridia, iridocorneal synechiae, as well as Peters, Axenfeld, and Rieger anomalies. Here, we report a large five-generation Caucasian family exhibiting atypical syndromic ASD segregating with a novel truncating variant of FOXC1. The family history is consistent with highly variable autosomal dominant symptoms including isolated glaucoma, iris hypoplasia, aniridia, cataract, hypothyroidism, congenital heart anomalies, and cystic kidney disease. Whole exome sequencing revealed a novel variant [c.313_314insA; p.(Tyr105*)] in FOXC1 that disrupts the alpha-helical region of the DNA-binding forkhead box domain. In vitro studies using a heterologous cell system revealed aberrant cytoplasmic localization of FOXC1 harboring the Tyr105* variant, likely precluding downstream transcription function. Meta-analysis of the literature highlighted the intrafamilial variability related to FOXC1 truncating alleles. This study highlights the clinical variability in ASD and signifies the importance of combining both clinical and molecular analysis approaches to establish a complete diagnosis.

Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

Meaning understood in terms of teachability and learnability is crucial to Wittgenstein’s later work. As regards the resolution of philosophical problems – and epistemological problems in particular - this approach seems to posit a hierarchy of meaning that excludes endless deferral. This is the basis of Wittgenstein’s attack on philosophical scepticism. Derrida’s approach to language seems to require both non-hierarchy and endless deferral. Consequently fundamental to his concept of origin is identity and difference simultaneously, irreducibly, non-simply. One question is whether it is possible for there to be a compromise between the two philosophers: a hierarchy of meaning that does not in principle exclude endless deferral.

In this study, we introduce a new type curve in 3-dimensional space which called B-lift curve and we obtain the Frenet operators of the B-lift curve. Moreover, we consider the correpondence of Frenet operators between the Blift curve and the natural lift curve. Finally, we investigate the B-lift curve according to the main curve is slant helix or darboux helix.

Immunotherapy has been considered for years as a viable and attractive treatment option for patients with cancer. Among immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionized the treatment of several subtypes of tumours. These approaches aimed at restoring an effective anti-tumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells, and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because in these diseases the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and will build a projection of how the field may evolve in the near future. In particular, we will analyze the current strategies being evaluated both preclinically and clinically with the aim to foster the use of immune-checkpoint inhibitors in non-Hodgkin lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies.

B chromosomes are supernumerary chromosomes which are found in addition to the normal standard chromosomes (A chromosomes). B chromosomes are well known to accumulate several types of repeats. Although the evolution of B chromosomes has been subject of numerous studies, the mechanisms of accumulation and evolution of repetitive sequences is not fully understood. Recently, new genomic approaches have shed light on the origin and accumulation of different classes of repetitive sequences in the process of B chromosome formation and evolution. Here we discuss the impact of repetitive sequences accumulation on the evolution of plant B chromosomes.

Bacteria’s ability to withstand the detrimental effects of antimicrobials may take the form of resistance or tolerance with the minimum inhibitory concentration (MIC), the mutant prevention concentration (MPC), and the mutant selection window as salient concepts. Isolates exposed for 30 days to different concentrations of selected antibiotics, biocides, and heavy metals, singly and in combination, were additionally exposed to very high (15 × MIC) concentrations of ampicillin., and their tolerance was calculated the time to kill 99.9% of the isolate population (MDK99.9). These values were increased by 30 to 50% in test isolates compared to the untreated control. BAC 10-exposed isolates had the highest tolerance increase, and the tolerance appeared to originate from two sources, i.e., stochastic persistence and genetic-induced persistence, involving multiple genes using diverse mechanisms. The mutant selection window of the isolates to ampicillin, amoxicillin, and oxytetracycline also slightly increased compared to the control, indicating the amplification of persister cells during the 30-day exposure. These findings indicate that bacterial exposure to sub-inhibitory concentrations of environmental chemical stressors may not always result in the development of antimicrobial resistance but could initiate this process by selecting for persisters that could evolve into resistant isolates.

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs), or antimicrobial peptides (AMPs) together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this communication, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition.

At 12:28 UTC (8:28 PM, local time) on 15 January 2023, a shallow, moderate earthquake with a magnitude (Mw) of 4.7 and a depth of one (1) kilometer shook the northern part of Leyte Island in the central part of the Philippines. The ground shaking was felt at PHIVOLCS Earthquake Intensity Scale (PEIS) VI, (very strong) equivalent to Modified Mercalli Intensity (MMI) VI in areas along the strike of the Leyte segment of the Philippine Fault. Even though this earthquake is classified as moderate in size, significant geologic, structural, and socio-economic impacts were documented. Most of the earthquake impacts that include surface rupture, liquefaction, and mass movements are limited near the epicentral area. The earthquake produced an 8-km-long surface rupture, the first documented rupture generated by a magnitude &lt;6 along the Philippine Fault, and is unusual in other surface rupturing earthquakes worldwide. It injured 18 persons and damaged 434 residential buildings and 26 public infrastructures which amounts to about 500 thousand US dollars. Structural damages were caused by surface rupture and/or poor engineering construction practices. Analysis of the seismic waveform and recorded peak ground acceleration (PGA) suggests that the subsurface geology influenced the ground motion amplification in an area near the epicenter. Based on the hypocenter, focal mechanism solution, aftershock distribution, and actual field observation, the causative fault for this event is the northern end of the Philippine Fault – Leyte segment. Moderate in size, this earthquake emphasizes the need and importance of documenting moderate-sized earthquakes as a tool and guide for medium and long-term earthquake risk assessment and resiliency.

Coal currently accounts for over 38% of electric power generation around the globe. Hence, it is a significant critical contributor to socio-economic growth and development, particularly in the BRIC economies. The success of the coal energy in these nations in addition to the discovery of vast new coal deposits have revived Nigeria’s interest in coal power. However, there is lack of comprehensive data on the pollution emission profiles, along with the physicochemical, thermal, and kinetic properties of Nigerian coals as required for power plant operations. Therefore, this paper presents preliminary findings on the physicochemical, microstructural, mineralogical and thermal properties of Owukpa (WKP) coal from Benue State in Nigeria. The results showed that WKP contains high compositions of combustible elements and heating value but low pollutant elements. Furthermore, thermal degradation revealed high conversion efficiencies particularly under oxidative conditions as required for electric power generation through combustion.

Background. Malignant pleural mesothelioma (MPM) is still a rather incurable disease. Many classes of compounds with various mechanisms of action have been tested in vivo and ex-vivo, with rather disappointing results. This is partly due to preclinical studies mostly performed in models that fail to recapitulate MPM complexity and do not retain the intra-tumor heterogeneity, a propelling force for tumor progression. Additionally, we and others have shown that, under stress-induced chemotherapy, profound rearrangements take place in MPM cultures to fuel the emergence of chemoresistant cell subpopulations. Thus, finding clinically actionable modulators of MPM resistance is still a very urgent need. Methods. Setup and propagation of patient-derived organoid cultures from MPM pleural effusions; flow cytometry-based validation of organoid cultures, isola-tion and propagation of mesothelioma-associated fibroblasts; co-cultures, Lu-minex-based Cytokine array, ELISA assay to quantitate IL-6 in the conditioned media, qRT-PCR to assess mRNA expression of cancer stem cell markers and fibroblast markers. Results. Organoid cultures were obtained from eight MPM patients by using specific growth media and conditions to propagate pleural effusion-derived cells. We proved that primary MPM specimens and serially passaged (mesothelio-ma-Patient-Derived-Organoids) mPDOs were cytologically similar, with the obtained mPDOs expressing mesothelial markers similarly to the originating specimen. As expected from a clinically relevant model, the size and number of mPDOs were altered, in a patient-specific way, when pharmacologically relevant doses of chemotherapy drugs were added. We derived Mesothelio-ma-Associated-Fibroblasts (MAFs) and the addition of MAFs, to various ratios, altered the response of the mPDOs to pemetrexed + cisplatin, toward a reduced sensitivity to the latter anticancer agents. Additionally, organoid formation and size were altered by MAF-conditioned media, and this correlated with increased expression of cancer stem cell markers. We showed increased levels of IL-6 in the media of the treated cocultures and showed that this latter was derived from the MAFs. Conclusions. Increased secretion of IL-6 by mesothelioma-associated fibroblasts (MAFs) contributes to the resistance of the MPM to therapy.

To define and evaluate the areas of consideration concerning in identifying the critical factors that top universities in Nueva Ecija, Philippines can be used for triangulating the courses of actions that can be applied to improve the current practices of universities towards its combat to the COVID–19 disease is the primary objective of this study. The researchers used a descriptive design of methodology by using questionnaire–checklist to scientifically describe the situation, problems, phenomenon, or program, or provide information about certain issues related to the virus outbreak. The respondents of the study were faculty and staff of five established universities in Nueva Ecija, Philippines wherein the researchers employed a non–probability sampling technique to be logically assumed as the representative of the entire population. The results of the study shown that the top universities in Nueva Ecija have made efforts to ensure the safety of university workers by complying with the Inter–Agency Task Force (IATF) protocols. It can be inferred, in reality, that there are some areas that must be improved especially when it comes to ensuring the welfare of the personnel who are still reporting to work even in this time of the pandemic. The researchers suggested an enhancement plan that can be adapted by these universities to resolve the concerns of the faculty and staff especially in reducing the spread of the virus without sacrificing the day–to–day transactions of the academic institutions.

Every finite simple group P can be generated by two of its elements. Pairs of generators forP are available in the Atlas of finite group representations as (not necessarily minimal) permutation representations P . It is unusual but significant to recognize that a P is a Grothendieck’s dessin d’enfant D and that a wealth of standard graphs and finite geometries G - such as near polygons and their generalizations - are stabilized by a D. In our paper, tripods P − D − G of rank larger than two,corresponding to simple groups, are organized into classes, e.g. symplectic, unitary, sporadic, etc (as in the Atlas). An exhaustive search and characterization of non-trivial point-line configurationsdefined from small index representations of simple groups is performed, with the goal to recognize their quantum physical significance. All the defined geometries G's have a contextuality parameterclose to its maximal value 1.