The theory of heavy ion double charge exchange (DCE) reactions proceeding by effective rank–2 isotensor interactions is presented. Virtual pion–nucleon charge exchange interactions are investigated as the source for induced isotensor interactions, giving rise to the Majorana DCE (MDCE) reaction mechanism. MDCE is of a generic character, proceeding through pairs of complementary (π±,π∓) reactions in the projectile and target nucleus. The dynamics of the elementary processes is discussed where the excitation of pion–nucleon resonances are of central importance. Investigations of initial and final state ion–ion interactions show that these effects are acting as vertex renormalizations. In closure approximation, well justified by the finite pion mass, the second order transition matrix elements reduce to pion potentials and effective two–body isotensor DCE interactions, giving rise also to two–body correlations in either of the participating nuclei. Connections to neutrinoless Majorana double beta decay (MDBD) are elucidated at various levels of dynamics, from the underlying fundamental electro–weak and QCD scales to the physical scales of nuclear MDBD and MDCE physics. It is pointed out that heavy ion MDCE reactions may also proceed by competing electro–weak charge exchange processes, leading to lepton MDCE by electrons, positrons, and neutrinos.

The statistical analysis of impact of the top 50 solar flares of X-class (1997-2023) on the global seismic activity, as well as on the earthquake preparation zones located in illuminated part of the globe and in the area of 5000 km radius around the subsolar point was carried out. It is shown by a method of epoch superposition that for all cases the increase of seismicity is observed, especially in the region around the subsolar point (up to 38%) during 10 days after the solar flare in comparison with preceding 10 days. The case study of aftershock sequence of strong M=9.1 earthquake (Su-matra-Andaman Islands, 26.12.2004) after the solar flare of X7.2 class (20.01.2005) demonstrated that the number of aftershocks with magnitude M≥2.5 increases more than 20 times after the solar flare with a delay of 7 days. For the case of the Darfield earthquake (M=7.1, 04.09.2010, New Zealand) it was shown that strong solar flares of class X and M probably triggered two strong aftershocks (M>6) with the same delay of 6 days on the Port Hills fault, which is the most sensitive to external electromagnetic impact from point of view of the fault electrical conductivity and orientation. Based on the obtained results the possible application of natural electromagnetic triggering of earthquakes is discussed for a short-term earthquake prediction using confidently recorded strong external electromagnetic triggering impacts on the specific earthquake preparation zones, as well as ionospheric perturbations due to aerosol emission from the earthquake sources recorded by satellites.

Earthquakes often entail alterations in the groundwater flow regime, in the phreatic level, in the surge and loss of springs, and discharge in brooks and springs. As for the latter, there are diverse feasible mechanisms, so there is a variety of theoretical approaches to elucidate the post-earthquake effects on spring discharge. This study adopts a conceptual approach, primarily presenting various methods for estimating water released by earthquakes by calculating discharge surpluses in springs. This study delves into refined techniques rooted in groundwater hydraulics, displaying applications of analytical and simulation methodologies to quantify seismic-induced groundwater discharge in springs. Investigating springs as natural indicators, this research applies mathematical precipitation-runoff models, specifically the CREC model, for simulating hydrographs in post-earthquake scenarios. We apply analytical procedures or mathematical simulation techniques employed in groundwater hydraulics for natural aquifer recharge calculations. Firstly, we briefly describe the methods based on the analysis of depletion curves of hydrographs in spring discharge. Additionally, certain mathematical rainfall-runoff models utilized in simulating hydrographs of karstic springs, along with derived analytical approximations, are adapted for this scenario. These hydraulic calculations involve the depletion coefficient and hydrodynamic volumes of aquifers, parameters that reveal certain aspects of the relation between groundwater and earthquakes, such as: a) Acknowledging faults as the primary geological structures in transmitting pore pressures due to earthquakes. b) Clarifying mechanisms of permeability enhancement during earthquakes. c) Highlighting the substantial volumes in motion within the Earth's interior, which, for instance, could constitute a significant source for the origin of mineral deposits. The findings highlight diverse features of the complex interplay between hydrogeological and tectonic processes at challenging spatial and temporal scales.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It was demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities. Methods: We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines. Results: We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and on lung fibroblast lines derived from fibrotic lungs but it is almost absent in control lines and tissue. CCL18 induces receptor-internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduces CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knock-down of CCR6 in a mouse fibroblast cell line abolishes the induction of collagen and -smooth muscle actin expression. Conclusion: Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.

Nonlinear properties of zinc germanium diphosphide (ZGP) crystals enable their ap-plications in powerful mid-IR optical parametric oscillators and second-harmonic generators. This paper summarizes mechanisms of the laser induced damage (LID) in high-purity ZGP crystals under periodically pulsed nanosecond irradiation by a Ho3+:YAG laser at 2.1 μm. The ZGP samples were manufactured by “LOC” Ent., Tomsk, Russia, or Harbin Institute of Technology, China. The impact of processing techniques and the post-growing methods for polishing and anti-reflection coating on the LID threshold are discussed. The importance of the defect structure of the crystal lattice and the parameters of transparent coatings for increasing the LID threshold is discussed. The impact of the test laser parameters on the LID threshold is analyzed. The transient area near the LID threshold obtained using digital holography is ana-lyzed. Influence of the pre-damage processes on the optical parametric oscillations is reported. Prospects for improving ZGP crystals to further increase the LID threshold are discussed.

Drug-induced pruritus triggers a desire to scratch, thereby diminishing one’s quality of life. Certain instances of this phenomenon follow complex mechanisms of action that diverge from histamine-mediated pathways, known contributors to pruritus. However, investigations into the relationship between drugs and pruritus are limited. In this study, data mining techniques were employed to comprehensively analyze the characteristics of drugs linked to pruritus, using the FDA Adverse Event Reporting System(FAERS) Data maintained in the United States. Reports linked to pruritus demonstrated noteworthy differences in gender, age, and weight when compared with non-pruritus cases. Among the leading candidates for drugs prompting pruritus were ophthalmic drugs, systemic antibacterials, contrast media, dermatological antifungals, and dermatological preparations. Principal component analysis showed that the second principal component served as an indicator for distinguishing between onsets at mucous membranes or the skin surface. Additionally, the third principal component functioned as an indicator for categorizing administration methods as either invasive or noninvasive. Furthermore, a hierarchical cluster analysis conducted on these obtained principal components revealed the potential for classifying drugs based on the site of pruritus onset and the method of drug administration. These findings contribute to the development of targeted prevention and treatment strategies for avoiding pruritus in clinical practice.

The time-resolved CIDNP method can provide information about degenerate exchange reactions (DEE) involving short-lived radicals. In the temperature range from 8 to 65°C, the DEE reactions of the guanosine-5’-monophosphate anion GMP(-H)- with the neutral radical GMP(-H)•, of the N-acetyl tyrosine anion NacTyrO- with a neutral radical NacTyrO• and of the tyrosine anion TyrO- with a neutral radical TyrO• were studied. In all the studied cases, the radicals were formed in the reaction of quenching triplet 2,2’-dipyridyl. The reorganization energies were obtained from Arrhenius plots. The rate constant of the reductive electron-transfer reaction in pair GMP(-H)•/TyrO- was determined at T = 25°C. Rate constants of GMP(-H)• radical reduction reactions with TyrO- and NacTyrO- anions calculated by the Marcus cross relation differ from the experimental ones by two orders of magnitude. The rate constants of several other electron transfer reactions involving GMP(-H)-/•, NacTyrO-/•, and TyrO-/• pairs calculated by cross relation agree well with the experimental values. The rate of nuclear paramagnetic relaxation was found for the 3,5 and β-protons TyrO• and NacTyrO•, the 8-proton GMP(-H)• the 3,4-protons DPH• at each temperature. In all cases, the dependences of the rate of nuclear paramagnetic relaxation on temperature are described by the Arrhenius dependence.

Volumetric modification of transparent materials by femtosecond laser pulses is successfully used in a wide range of practical applications. The level of modification is determined by the locally absorbed energy density, which depends on numerous factors. In this work, it is shown experimentally and theoretically that, in a certain range of laser pulse energies, the peak of absorption of laser radiation for doughnut-shaped (DS) pulses is several times higher than for Gaussian ones. This makes the DS pulses very attractive for material modification and direct laser writing applications. Details of the interaction of laser pulses of Gaussian and doughnut shapes with fused silica obtained by numerical simulations are presented for different pulse energies and compared with the experimentally obtained data. The effect of absorbed energy delocalization with increasing laser pulse energy is demonstrated for both beam shapes while, at relatively low pulse energies, the DS beam geometry provides a stronger local absorption compared to Gaussian one. Implications of a DS pulse action on post-irradiation material evolution are discussed based on thermoelastoplastic modeling.

Abstract: The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state,” has the potential to cause a deleterious effect on clock gene expression and disrupted regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, appetite and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases. The consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantage of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

Genetic sensorineural hearing loss and Meniere disease have been associated with rare variations in the coding and non-coding region of the human genome. Most of these variants are classified as likely pathogenic or variants of unknown significance and require functional validation in cellular or animal models. Given the difficulties to obtain human samples and the raising concerns about animal experimentation, human induced pluripotent stem cells emerge as cellular models to investigate the interaction of genetic and environmental factors in the pathogenesis of inner ear disorders. The generation of human sensory epithelia and neuron-like cells carrying the variants of interest may facilitate a better understanding of their role during differentiation. These cellular models will allow us to explore new strategies for restoring hearing and vestibular sensory epithelia as well as neurons. This review summarizes the use of human induced pluripotent stem cells in sensorineural hearing loss and Meniere disease and proposes some strategies for its application in clinical practice.

Plasmodium falciparum dihydroorotate dehydrogenase (PfDODH) is one of the enzymes currently explored in the treatment of malaria. Although there is currently no clinically approved drug targeting PfDODH, many of the compounds in clinical trials have [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine backbone structure. This study sought to design new compounds from the fragments of known experimental inhibitors of PfDODH. Nine experimental compounds retrieved from Drug Bank online were downloaded and broken into fragments using Schrodinger power shell; the fragments were recombined to generate new ligand structures using BREED algorithm. The new compounds were docked with PfDODH crystal structure, after which the compounds were filtered with extensive drug-likeness and toxicity parameters. A 2D-QSAR model was built using the multiple linear regression method and externally validated. The compounds electronic behaviours were studied using DFT calculations. Structural investigation of the six designed compounds, which had lower binding energies than the standard inhibitors, showed that five of them had [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine moieties and interacted with essential residues at the PfDODH binding site. In addition to their drug-like and pharmacokinetic properties, they also showed minimal toxicities. The externally validated 2D-QSAR model with R² and Q² values of 0.6852 and 0.6691, confirmed the inhibitory prowess of these compounds against PfDODH. The DFT calculations showed regions of the molecules prone to electrophilic and nucleophilic attack. The current study thus provides insight into the development of a new set of potent PfDODH inhibitors.

Introduction: Wound healing is a multifaceted biological process, and diabetic wounds add more complexity to it. In diabetic wounds, the combination of chloroform fractions of Achyranthes aspera L. (A.aspera) leaves with β-Glucans has not been investigated. The additive effect of these two (A.aspera + β-Glucans) would benefit the inflammatory phase of diabetic wounds, as improper treatment will lead to chronic injuries. Therefore, the goal of this research work was to assess the in-vivo wound healing and anti-inflammatory effects of a combination of chloroform fractions of A.aspera leaves and β-Glucans in a variety of wound models in STZ-induced diabetic rats. Methods: Preliminary phytochemical analyses of A.aspera were conducted to identify various phytoconstituents in the test extract. Acute and sub-acute dermal toxicity tests of A.aspera were carried out on mice and rats, respectively, to see whether there were any abnormalities. Excision and incision wound models, cotton pellet-induced granuloma models, rat paw edema and burn wounds were used to test wound healing and anti-inflammatory actions. To induce diabetes, streptozotocin (STZ) was administered intraperitoneally at a dosage of 65 mg/kg (i.p.). A.aspera (10% w/w) and β-Glucans (2% w/w) ointments were tested separately and in combination for wound healing activities. Silver sulfadiazine (1 % w/w) ointment was used to treat the positive control groups. Excision wound model rats that had been treated with basic ointment were used as negative controls, as were incision wound model rats that had not been treated. A.aspera (400 mg/kg, po) and β-Glucans (30 mg/kg, po) were tested separately and in combination for anti-inflammatory efficacy. Positive control groups were given indomethacin (10 mg/kg, po) for cotton pellet-induced granuloma and rat paw oedema models. Negative controls for both anti-inflammatory activity models were provided 2% Tween 80. The groups were made up of six rats, and the treatments were given topically and orally to assess wound healing and anti-inflammatory effects. The levels of hydroxyproline and hexosamine and the antioxidant enzymes (SOD and CAT) in the granulation tissue were measured in excision wound model. Healed excision wound skin was examined histopathologically. Results: The A.aspera and β-Glucans combination resulted in a significant percentage of wound contraction and a shorter epithelialization time (P<0.01). The combination was found to be the most effective, with the highest percentage of edema reduction (55 %; p<0.01). The combination also exhibited favourable hydroxylamine, hexosamine and anti-oxidant profiles supported by histopathology data. Conclusion: This research showed that the immunomodulatory effect of β-Glucans had significantly enhanced the wound healing, anti-inflammatory, and anti-oxidant potential of A.aspera in diabetic wounds.

Keywords: Chemical Intolerance, Drug Intolerance, Food Intolerance, QEESI, BREESI, Multiple Chemical Sensitivity, Toxicant-induced Loss of Tolerance, Prevalence

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

Recently, several research groups have reported on anomalous enhancement of the self-field critical currents, Ic(sf,T), at low temperatures in superconductor/Dirac-cone material/superconductor (S/DCM/S) junctions. Some papers attributed the enhancement to the low-energy Andreev bound states arising from winding of the electronic wave function around DCM. In this paper, Ic(sf,T) in S/DCM/S junctions have been analyzed by two approaches: modified Ambegaokar-Baratoff and ballistic Titov-Beenakker models. It is shown that the ballistic model is an inadequate tool to analyze experimental data from S/DCM/S junctions. The primary mechanism for limiting superconducting current in S/DCM/S junctions is different from the conventional view that the latter is the maximum value within the order parameter phase variation. Thus, there is a need to develop a new model for self-field critical currents in S/DCM/S systems.

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

This work communicates a review on Balmer series hydrogen beta line measurements and applications for analysis of white dwarf stars. Laser-induced plasma investigations explore electron density and temperature ranges comparable to white dwarf star signatures such as Sirius B, the companion to the brightest star observable from the earth. Spectral line shape characteristics of the hydrogen beta line include width, peak separation, and central dip-shift, thereby providing three indicators for electron density measurements. The hydrogen alpha line shows two primary line-profile parameters for electron density determination, namely, width and shift. Both Boltzmann plot and line-to-continuum ratios yield temperature. The line-shifts recorded with temporally- and spatially- resolved optical emission spectroscopy of hydrogen plasma in laboratory settings can be larger than gravitational redshifts that occur in absorption spectra from radiating white dwarfs. Published astrophysical spectra display significantly diminished Stark or pressure broadening contributions to red-shifted atomic lines. Gravitational redshifts allow one to assess the ratio of mass and radius of these stars, and subsequently, the mass from cooling models.

The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to free HPV vaccine is a public health concern. HPV is one of the most common Sexually Transmitted Infections (STIs) in Nigeria with high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) university located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on google form and it was distributed to the University community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, knowledge about HPV infection and genotypes, as well as sexual health of the participants. All variables were described using frequencies and percentage distribution, chi-squared test statistics was used to explore the association between HPV infection (medical records of HPV infection) and the participants’ profile, and logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26 – 40 years (81.3%) and those currently not in a union (26.4%) who have self-reported having HPV-16 and -18 genotypes. Also, participants between 26 – 40 years of age (OR: 0.45, 95%CI: 0.22 – 0.89) reported to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Alzheimer's disease (AD) remains a significant challenge in the field of neurodegenerative disor-ders, even nearly a century after its discovery, due to the elusive nature of its causes. The develop-ment of drugs that target multiple aspects of the disease has emerged as a promising strategy to address the complexities of AD and related conditions. The immune system's role, particularly in AD, has gained considerable interest, with nanobodies representing a new frontier in biomedical research. Advances in targeting antibodies against amyloid-β (Aβ) and using messenger RNA for genetic translation have revolutionized the production of antibodies and drug development, open-ing new possibilities for treatment. Despite these advancements, conventional treatments for AD, such as Cognex, Exelon, Razadyne, and Aricept, often have limited long-term effectiveness, under-scoring the need for innovative solutions. This necessity has led to the incorporating of advanced technologies like artificial intelligence and machine learning into the drug discovery process for neurodegenerative diseases. These technologies help identify therapeutic targets and optimize lead compounds, offering a more effective approach to addressing the challenges of AD and similar conditions.

Myocarditis has been recognized as a possible rare complication of COVID-19 mRNA vaccination. It concerns between one and five vaccinated people per 100,000 in the general population, with increased incidence in adolescent and young adult men. Most often, cases of myocarditis have been reported in the days following the second dose of vaccine mainly in younger male patients. This rare complication of vaccination usually resolves within days or weeks. However, the pathophysiological events responsible for the increase in frequency of myocarditis after COVID-19 vaccination remain unclear. Several recent reports have highlighted that free spike proteins circulating in the blood of patients at high levels appear to play a major role in myocarditis. Here, we review the most relevant data that partly lift the veil on the molecular mechanisms of the induction of myocarditis following mRNA-based COVID-19 vaccination. We hypothesize that a mechanism of molecular mimicry of the viral spike triggers transient dysregulation of angiotensin-converting enzyme 2, leading to increased soluble angiotensin II binding to the transmembrane receptor angiotensin II type I receptor, similar to what is observed during SARS-CoV-2 infection. We suggest to standardize management of suspected cases of mRNA-based COVID-19 vaccine-induced myocarditis, including angiotensin II and spike antigenemia monitoring.

Background: This study delves into the examination of racial and ethnic disparities in the distribution of the Monkeypox (MPOX) virus vaccine within the United States, offering a critical healthcare perspective on an emerging public health concern. It particularly focuses on the demographic patterns associated with MPOX transmission and the allocation of vaccines. Methods: A comprehensive analysis was conducted, drawing on a wide array of data sources to understand the vaccine distribution and demographic trends in the United States. The study scrutinized three main aspects: MPOX cases by race and ethnicity, vaccine administration across different racial and gender categories, and the potential disparities therein. Results: The findings reveal significant disparities in the distribution of vaccine doses, with males, particularly gay, bisexual, and other Men who have sex with men (MSM), receiving the majority of doses. Moreover, substantial variations in MPOX cases are observed among different racial and ethnic groups, emphasizing the need for culturally sensitive public health strategies. Conclusions: The study underscores the urgent need for targeted public health interventions to address disparities and safeguard the well-being of those at higher risk, particularly MSM. It highlights the importance of equity in vaccine distribution and culturally sensitive approaches, and serves as a foundation for shaping effective public health policies and strategies to mitigate the spread of MPOX. This research advances our understanding of healthcare disparities in the context of an emerging viral infection, providing valuable insights for future public health initiatives.

African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. Currently, there is no ASF vaccine commercially available. All infected animals must be isolated and culled immediately upon confirmation of the presence of the virus. Works leading to the rational development of protective ASF vaccines are urgently needed. Here, we generated a safe and efficacious live-attenuated vaccine (LAV) VNUA-ASFV-LAVL2 by serial passaging of a field isolate (VNUA-ASFV-05L1, genotype II) in porcine alveolar macrophage (PAMs, 65 passages) and an immortalized porcine alveolar macrophage cell line (3D4/21, 55 passages). VNUA-ASFV-LAVL2 can efficiently replicate in both PAMs and 3D4/21 cells. It provides 100% protection, even with the low dose of 10^2 HAD50, for the vaccinated pigs against the challenge of contemporary pandemic ASFV field isolate. Pigs vaccinated with this LAV at a dose range of 10^2 to 10^5 HAD50 remained clinically healthy during both the 28-day observation period of immunization and the 28-day observation period of challenge. VNUA-ASFV-LAVL2 was completely eliminated from blood by 28 days post inoculation (DPI), and from feces or oral fluids by 17 DPI. It remained a safe, stable, and attenuated phenotype after five passages in pigs. Consistently high levels of ASFV-specific IgG antibodies and significant cellular immunity were detected in vaccinated pigs before the ASFV challenge. These results indicate that the VNUA-ASFV-LAVL2 strain is a safe and efficacious LAV against the genotype II ASFV strain responsible for current ASF outbreaks in Asia.

The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant of concern has been the dominant cause of worldwide COVID-19 cases since 2022. All the Omicron sublineage viruses have demonstrated high transmissibility and an ability to escape vaccine-induced immunity. While first-generation vaccines, including monovalent vaccines, continue to provide protection against severe disease, hospitalization and mortality, their efficacy against Omicron sub variants remains sparse. These vaccines have also been associated with rapidly waning protection against primary COVID-19 and COVID-19 reinfections conferred by evolving Omicron sublineages.. This led to the development and deployment of updated vaccines and the introduction of the bivalent booster. Through this review, we highlight the brief journey of the variants of concern leading to the dominance of Omicron and the effectiveness of the key vaccines against these variants, including the updated (bivalent) boosters.

Tuberculosis (TB) is still a worldwide major health problem and models using non-human primates (NHP) provide the most relevant approach for vaccine testing. In this study we have analysed CT images collected from cynomolgus and rhesus macaques, following exposure to ultra-low dose Mycobacterium tuberculosis (Mtb) aerosols, and monitored them for 16 weeks to evaluate the impact of prior intradermal or inhaled BCG-vaccination on the progression of lung disease. All lesions found (2553) have been classified according to their size and we have subclassified small micronodules (<4.4 mm) as ‘isolated’, or as ‘daughter’ when they are in contact with consolidation (described as lesions ≥ 4.5 mm). Our data links the higher capacity to contain Mtb infection in cynomolgus with the reduced incidence of daughter micronodules, thus avoiding the development of consolidated lesions and their consequent enlargement and evolution to cavitation. In the case of rhesus, intradermal vaccination has a higher capacity to reduce the formation of daughter. This study supports the ‘Bubble Model’ defined with the C3HBe/FeJ mice and proposes a new method to evaluate outcome in experimental models of TB in NHP based on CT images, which would fit a future machine learning approach to evaluate new vaccines.

Nasal cavity is a primary checkpoint for the invasion of several respiratory pathogens. Numerous pathogens including SARS-CoV-2, S. pneumonia, S. aureus, etc., adhere to the nasal epithelium or mucus to invade and trigger an infection. IgA serves as the first line of defense against foreign antigens and pathogens. They exhibit cross-reactivity against a diverse variety of antigens through immune exclusion, which intercepts the invasion of pathogens through the mucosal lining. Advances in intranasal immunization technology underscore the elevated neutralizing IgA levels at local and distal mucosa in contrast to the parenteral vaccines. This review highlights the adjuvants that induce IgA class switching and the challenges of maintaining nominal IgA levels at the mucosal surface. Finally, the review features the paradigm-shifting of conventional immunization techniques to IgA-inducing vaccines to enhance protection against homologous and heterologous pathogens.

Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1-4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1-4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1-4) Philippine isolates.

Neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. Analysis of ZIKV epidemic strains showed that glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS.

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

The worldwide outbreak of a novel coronavirus, SARS-CoV-2 has caused a pandemic of respiratory disease. Due to this emergency, researchers around the globe have been investigating the evolution of the genome of SARS-CoV-2 in order to design vaccines. Here I examined the evolution of GC content of SARS-CoV-2 by comparing the genomes of the members of the group Betacoronavirus. The results of this investigation revealed a highly significant positive correlation between the GC contents of betacoronaviruses and their divergence from SARS-CoV-2. The betacoronaviruses that are distantly related to SARS-CoV-2 have much higher GC contents than the latter. Conversely, the closely related ones have low GC contents, which are only slightly higher than that of SARS-CoV-2. This suggests a systematic reduction in the GC content in the SARS-CoV-2 lineage over time. The declining trend in this lineage predicts a much-reduced GC content in the coronaviruses that will descend/evolve from SARS-CoV-2 in the future. Due to the three consecutive outbreaks (MERS-CoV, SARS-CoV and SARS-CoV-2) caused by the members of the SARS-CoV-2, the scientific community is emphasizing the need for universal vaccines that are effective across many strains including those, that will inevitably emerge in the near future. The reduction in GC contents implies an increase in the rate of GC→AT mutations than that the mutational changes in the reverse direction. Therefore, understanding the evolution of base composition and mutational patterns of SARS-CoV-2 could be useful in designing broad-spectrum vaccines that could identify and neutralize the present and future strains of this virus.

Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

In this paper, we proposed a novel saddle type FinFET (S-FinFET) to effectively solve problems occurring under the capacitor node of dynamic random-access memory (DRAM) cell and showed how its structure was superior to conventional S-FinFETs in terms of short channel effect (SCE), subthreshold slope (SS), and gate-induced drain leakage (GIDL). The proposed FinFET exhibited 4 times lower Ioff than modified S-FinFET called RFinFET with more improved DIBL characteristics while minimizing Ion reduction compared to RFinFET. Our results also confirmed that the proposed device showed improved DIBL and Ioff characteristics as gate channel length decreased.

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the amyloid precursor protein (APP) gene. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

Angiotensin-converting enzyme (ACE) inhibitors are used primarily in the treatment of hypertension, heart failure, and in the acute phase of myocardial infarction. Lisinopril [N2-[(1S)-1-car-boxy-3-phenylpropyl]-L-lysyl-L-proline], enalapril [(S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline] and ramipril [2-aza-bicyclo-[3.3.0]-octane-3-carboxylic acid] are all five-membered heterocycles and three of the most prevalent ACE inhibitors in clinical use worldwide. ACEi-induced angioedema (ACEi-AE) is clinically characterized by self-limited edema of the dermis and subcutaneous lipid tissue, localized on face skin, oral mucosa and tongue in most cases. However, severe episodes of intestinal AE misdiagnosed as acute appendicitis and laryngeal AE requiring incubation have been reported. The pathophysiology of ACEi induced-AE is attributed to the accumulation of bradykinin, which is a potent vasodilator with proinflammatory activity that is normally degraded by angiotensin-converting enzyme (ACE) and aminopeptidase P; however, a small proportion of treated patients is affected. Given that patients do not respond to anti-H1 antihistamines and steroids, the early clinical recognition and the ACEi discontinuation are the treatment of choice for the long term management of ACEi-AE.

Graphene materials synthesized using direct laser writing (laser-induced graphene; LIG) are fa-vorable sensor materials because of their large surface area, ease of fabrication, and cost effec-tiveness. In particular, LIG decorated with metal nanoparticles (NPs) has been used in various sensors, including chemical sensors and electronic and electrochemical biosensors. However, the effect of metal decoration on LIG sensors remains controversial; hypotheses based on computa-tional simulations do not always match experimental results, and even experimental results re-ported by different researchers have not been consistent. In the present study, we explored the effects of metal decorations on LIG gas sensors, with NO2 and NH3 gases as representative oxi-dizing and reducing agents, respectively. To eliminate unwanted side effects arising from metal salt residues, metal NPs were directly deposited by vacuum evaporation. Although the gas sen-sitivities of the sensors deteriorate upon metal decoration irrespective of the metal work function in the case of NO2 gas, they improve upon metal decoration in the case of NH3 exposure. A careful investigation of the chemical structure and morphology of the metal NPs in the LIG sensors shows that the spontaneous oxidation of metal NPs with a low work function changes the be-havior of the LIG gas sensors and that the sensor behaviors under NO2 and NH3 gases follow different principles.

In a recent paper, we extended previous studies on solar-terrestrial relationships by investigating the origin of the March 2012 heatwave in northeast USA. In the present study we check the possible relationship of solar activity with the early March 2012 bad weather in northeast Thrace, Greece. To this end, we examined data from various remote sensing instrumentation monitoring the Sun (SDO satellite), the Interplanetary Space (ACE satellite), the Earth’s magnetosphere (Earth based measurements, NOAA-19 satellite), the top of the clouds (TERRA and AQUA satellites) and the near ground atmosphere. Our comparative data analysis suggests that: (i) the winter-like weather (rainfall, fast winds, decreased temperature) in Thrace started on 6 March 2012, on the same day as the heatwave starting in USA, (ii) during the March 2012 winter-like event in Thrace (6-15 March), the ACE satellite recorded enhanced fluxes of solar energetic particles (SEPs), while SOHO and PAMELA recorded solar protons at very high energies (> 500 MeV), (iii) Thrace experienced particularly intense cyclonic circulation, during periods of magnetic storms on 8 - 10 and 12-13 March, which occurred after the arrival at ACE of two interplanetary shock waves, on March 8 and March 11, respectively, (iv) at the beginning of the two above mentioned periods large atmospheric electric fields were recorded, with values ranging between ~-2000V/m - ~1800V/m on 8 March, (v) the winter-like 8-10 March 2012 weather occurred after the detection of the main SEP event related with a coronal mass ejection released in the interplanetary space as a result of intense solar flare activity observed by SDO on 7 March 2012, (vi) the 8-10 March weather was related with a deep drop of ~630C in the cloud top temperature measured by MODIS/TERRA, which favors strong precipitation. Finally, we analyzed data from the electric power network in Thrace (~410N) and we found, for the first time sudden voltage changes of ~3.5kV in the electric grid in Greece, during the decay phase of the March 2012 superstorm. We discuss the winter-like March 2012 event in Thrace in terms of solar cosmic ray influence on the low troposphere mediated by positive NAO. Finally, we infer that the novel finding of the geomagnetic effects on the electric power grid in Thrace may open a new window into space weather applications research.

Intelligent transportation systems (ITS) have recently evolved rapidly, which requires development of highly trustworthy and effective communication technologies for uses, including vehicle-to-vehicle (V2V) and vehicle-to-everything (V2X) communication; where Orthogonal Frequency Division Multiplexing (OFDM) is regarded as a strong candidate and highly popular option technique among these methods. However, the movement of vehicles introduces Doppler frequencies which produce inter-carrier interference (ICI), that is frequently occurs in V2X channels. This interference has the potential to compromise the integrity of subcarrier orthogonality within OFDM, leading to lower-quality communication and an increased likelihood of data transmission errors. When employing channels with doubly dispersive fading, OFDM necessitates the usage of a complex equalization based on the minimum mean-square error (MMSE) equalizer, which requires channel matrix inversion. Several low-complexity equalizers for OFDM have been developed and are based on band factorization, time domain LSQR (Least-Square QR) iterative computing, and banded minimum mean squared error (BMMSE). This paper proposes Conjugate Gradient Least Squares (CGLS), which is a novel iterative computation algorithm integrated with nonlinear equalizers. The suggested nonlinear equalization technique determines the trade-off between computations and performance. According to simulation data, the suggested nonlinear equalizer performs better than the current BMMSE and linear CGLS algorithms across doubly dispersive fading channels.

This work investigates a new nanostructured gas-diffusion-layer (nano-GDL) to improve performance of air-cathode Single-Chamber-Microbial-Fuel-Cells (a-SCMFCs). The new nano-GDLs improves the direct oxygen-reduction-reaction by exploiting the best of nanofibers from electrospinning in terms of high surface ratio to volume and high porosity, and laser-based processing to promote adhesion. Nano-GDLs by electrospinning were fabricated directly collecting two nanofibers mats on the same carbon-based electrode, acting as the substrate. Each layer was designed with a specific function: water resistant, oxygen permeable polyvinylidene-difluoride (PVDF) nanofibers served as a barrier to prevent water-based electrolyte leakage, while an inner layer of cellulose nanofibers was added to promote oxygen diffusion towards the catalytic sites. The maximum current density obtained for a-SCMFCs with the new nano-GDLs is (132.2 ± 10.8) mA m^-2, and it doubles the current density obtained with standard PTFE-based GDL (58.5 ± 2.4 mA m^-2), used as reference material. The energy recovery (EF) factor, i.e. the ratio of the power output to the inner volume of the device, was then used to evaluate the overall performance of a-SCMFCs. a-SCMFCs with nano-GDL provided an EF value of 60.83 mJ m^-3: one order of magnitude higher than the value of 3.92 mJ m^-3 obtained with standard GDL

Fluorophores with a tetraphenylethylene (TPE) core are attracting increasing interest because of their aggregation-induced emission (AIE) behaviour, which makes them particularly suitable when dispersed in thin-layer films. We propose the synthesis and use of a novel TPE fluorophore (hereafter called TPE-BPAN) decorated with two dimethylamino push groups and a 4-biphenylacetonitrile pull moiety. In tetrahydrofuran solutions, TPE-BPAN showed a broad absorption spectrum, and an intense emission is observed when a non-solvent as water is added in amounts of 70% and above. We selected and synthetized five different polymer matrices for TPE-BPAN with decreasing polarity: a) poly(methylmetacrylate) homopolymer (PMMA); b), c), and d) three copolymers of methyl methacrylate and cyclohexyl methacrylate at different compositions (P(MMA-co-CHMA) 75:25, 50:50, 25:75 mol%); e) poly(cyclohexyl methacrylate) homopolymer (PCHMA). The presence of a less polar comonomer as cyclohexyl methacrylate appeared to enhance the emission behaviour of TPE-BPAN, which displayed the highest quantum yield (QY) in P(MMA-co-CHMA) 75:25 in all the range of concentration studied from 0.4 wt.% to 2.0 wt.%. Further reduction in polarity lowered QY to the values of PMMA films; also, lower adhesion to the glass and a marked fragility of the films were observed. Referring to the P(MMA-co-CHMA) 75:25 films, QY values decreased from over 40% at 0.4 wt.% to about 30% at 2.0 wt.%, which is still helpful for energy harvesting applications such as luminescent solar concentrators (LSC). LSC performances were not significantly affected by the matrix's lower polarity and resulted in around one-third of the state-of-the-art due to the lower QY of TPE-BPAN. The theoretical investigation on density functional theory (DFT) clarified the origin of the observed AIE and the role played by the environment in modulating the photophysical behaviour.

Neuronal cell fate is predominantly controlled by the effects of growth factors, such as neurotrophins, and the activation of a variety of signaling pathways acting through neurotrophin receptors, namely Trk and p75 (p75NTR). Despite their beneficial effects on brain function, their therapeutic use is compromised, due to their polypeptidic nature and blood–brain-barrier impermeability. To overcome these limitations, our previous studies have proven that DHEA-derived synthetic analogs can act like neurotrophins, lacking endocrine side effects. The present study focuses on the biological characterization of a newly synthesized analog, ENT-A044, and its role on inducing cell specific functions of p75NTR. We show that ENT-A044 can induce cell death and phosphorylation of JNK protein by activating p75NTR. Additionally, ENT-A044 can induce the phosphorylation of TrkB receptor, indicating that our molecule can activate both neurotrophin receptors, leading towards the protection of neuronal populations that express both receptors. Furthermore, the present study demonstrates for the first time the expression of p75NTR in human induced Pluripotent Stem Cells - derived Neural Progenitor Cells (hiPSCs - derived NPCs) and receptor-dependent cell death induced by ENT-A044 treatment. In conclusion, ENT-A044 could be proven a lead molecule for the development of novel pharmacological agents, aiming on new therapeutic approaches and research tools, by controlling p75NTR actions.

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.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

Fabrics comprised of porous fibers could provide effective passive protection against chemical and biological (CB) threats whilst maintaining high air permeability (breathability). Here, we fabricate hierarchically porous fibers consisting of regenerated silk fibroin (RSF) and activated-carbon (AC) prepared through two fiber spinning techniques in combination with ice-templating – namely cryogenic solution blow spinning (Cryo-SBS) and cryogenic wet-spinning (Cryo-WS). The Cryo-WS RSF fibers had exceptionally small macropores (as low as 0.1 µm) and high specific surface areas (SSAs) of up to 79 m2 g-1. The incorporation of AC could further increase the SSA to 210 m2 g-1 (25 wt. % loading) whilst also increasing adsorption capacity for volatile organic compounds (VOCs).

There are numerous hazards found on the farms. Most of them are ignored, which might cause the farmer to pay later in terms of his ill health, potential injuries or death. The current article discusses some of the common issues such as dust and air quality concerns; environmental (weather) stressors and psychological stressors; noise and hearing protection; and tractor safety and seatbelt use. And finally, the recommendations to overcome the hazards are discussed.

Induction of jasmonate-mediated plant defense against insect herbivory is initiated by a combination of both, mechanical wounding and chemical factors. In order to study both effects independently on plant defense induction, SpitWorm, a computer-controlled device which mimics the damage pattern of feeding insect larvae on leaves and, in addition, can apply oral secretions (OS) or other solutions to the ‘biting site’ during ‘feeding’, was developed and evaluated. The amount of OS left by a Spodoptera littoralis larva during feeding on Phaseolus lunatus (lima bean) leaves was estimated by combining larval foregut volume, biting rate, and quantification of a fluorescent dye injected into the larvae’s foregut prior to feeding. For providing OS amounts by SpitWorm equivalent to larval feeding, dilution and delivery rate were optimized. The effectiveness of SpitWorm was tested by comparing volatile organic compounds (VOC) emissions of P. lunatus leaves treated with either SpitWorm, MecWorm or S. littoralis larvae. Identification and quantification of emitted VOCs revealed that SpitWorm induced a volatile bouquet that is qualitatively and quantitatively similar to herbivory. Additionally, RT-qPCR of four jasmonic acid responsive genes showed that SpitWorm, in contrast to MecWorm, induces the same regulation pattern as insect feeding. Thus, SpitWorm mimics insect herbivory almost identical to real larvae feeding.

Rice grassy stunt virus (RGSV) a member of Tenuivirus family, is very potent and destructive which effects rice crop in many countries, particularly China. Non coding RNAs have important functions in development and epigenetic regulation of gene expression in numerous organsisms. There is three type of small non coding RNAs have been found in eukaryotes, which are small interferring RNAs (siRNAs), microRNAs (miRNAs) and piwi interacting RNAs (piRNAs). Small RNAs (sRNAs) origination is from the infecting virus which is known as virus-derived small interfering RNAs (vsiRNAs), has responsibility for RNA silencing in plants. Virus-induced gene silencing (VIGS) is mainly dependent on RNA silencing (RNAi). Interestingly, RNA silencing happens in plants during viral infections. RNAi technique showed significant results in Nephotettix cincticeps. RNAi technique demonstrated the gene silencing of planthopper Nilaparvata lugens. The proteins P5, pcf4, Dnj, psn5, and pn6 act as potential movement proteins and serve as silencing suppressors for RGSV. VsiRNAs originate from dsRNA molecules which require Dicer-like (DCL) proteins, RNA dependent RNA polymerase (RdRP) proteins, and Argonaute (AGO) proteins. RdRP uses ssRNA for perfect RNA amplification process and can also be used for DCL dependent secondary vsiRNA formation. VSRs interfere with the movement of signals during silencing mechanism. Moreover, intercellular movement of viruses is facilitated by virus-encoded movement protein. RNAi is found in many eukaryotes which are related to transcriptional or post-transcriptional regulation by gene suppression. Transcription is bidirectional in ssDNA viruses which are originated from dsRNA molecules. In this review, we highlighted the biology of Rice grassy stunt virus and its insect vector and its silencing suppressors. This work will be helpful for plant virologists to understand the whole biogenesis mechanism for rice viruses especially RGSV.

The emergence of mRNA vaccines for SARS-CoV-2 has opened a new page in vaccine development; nevertheless, concerns of the experts have been expressed about unintentional side effects on the gut microbiota (GM). Previous studies showed that this virus acts as a bacteriophage, which infects and destroys specific bacterial strains in the GM. The present manuscript hypothesizes that the synthetic spike protein could create changes in the composition and the functioning of the GM by entering the intestinal cells after vaccination and impairing the symbiotic relationship between intestinal cells and the GM. An experimental protocol to test the hypothesis is suggested.

Personalized cancer vaccines have emerged as a promising avenue for cancer treatment or prevention strategies. This approach targets the specific genetic alterations in individual patient’s tumors, offering a more personalized and effective treatment option. Previous studies have shown that generalized peptide vaccines targeting a limited scope of gene mutations are ineffective, emphasizing the need for personalized approaches. While studies have explored personalized mRNA vaccines, personalized peptide vaccines have not yet been studied in this context. Pancreatic ductal adenocarcinoma (PDAC) remains challenging in oncology, necessitating innovative therapeutic strategies. In this study, we developed a personalized peptide vaccine design methodology, employing RNA sequencing (RNAseq) to identify prevalent gene mutations underlying PDAC development in a specific patient solid tumor tissue. We performed RNAseq analysis for trimming adapters, read alignment, and somatic variant calling. We also developed a Python program, called GeneFinder, which validates the alignment of the RNAseq analysis. The Python program is freely available to download. Using chromosome number and locus data, GeneFinder identifies the target gene along the UCSC hg38 reference set. Based on the gene mutation data, we developed a personalized PDAC cancer vaccine that targets 100 highly prevalent gene mutations in the individual patient. We predicted peptide-MHC binding affinity, immunogenicity, antigenicity, allergenicity, and toxicity for each epitope. Then, we selected the top 50 and 100 epitopes based on our previously published vaccine design methodology. Finally, we generated pMHC-TCR 3D molecular model complex structures which are freely available fo download. The designed personalized cancer vaccine contains epitopes commonly found in PDAC solid tumor tissue. Our personalized vaccine was composed of neoantigens, allowing for a more precise and targeted immune response against cancer cells. Additionally, we identified mutated genes which were also found in the reference study where we obtained the sequencing data, thus validating our vaccine design methodology. This is the first study designing a personalized peptide vaccine using human patient data to identify gene mutations associated with the specific tumor of interest.

Vaccination against the SARS-CoV2 virus has shown great promise in managing the spread and severity of Covid-19. While these vaccines were able to provide a favourable response in controlling the SARS-CoV2 infection, its use came with accompanying side effects. This systematic review aimed to determine the effectiveness of the different Covid-19 vaccine subtypes and discover the side effects associated with each vaccine elsewhere but specially in Trinidad and Tobago. For this systematic review, the keywords “Pfizer-BioNTech OR Moderna OR Oxford-AstraZeneca OR Janssen OR Sinopharm OR Novavax AND Covid-19 vaccine efficacy” and “Covid-19 vaccines AND Trinidad and Tobago” were researched under PubMed, MEDLINE and other internet sources through which other notable journals, and documents were discovered and searched similarly as outlined previously. In doing so, 65 relevant articles were included as part of this review. Of the studies examined, overall the vaccine with the greatest VE was found to be Pfizer-BioNTech (95%), followed by Moderna (94.1%), Novavax (89.7%), AstraZeneca (70.4%), Sinopharm (67%) and finally Janssen (66.9%). The use of Pfizer-BioNTech or Moderna was most efficacious in response to the different Covid-19 variants. Some side effects were common for all vaccine types however adverse effects were more commonly seen with vaccination by mRNA vaccines, Pfizer-BioNTech and Oxford-Astrazeneca. Researchers targeted individuals aged 18 and above residing in various geographical areas of TT, specifically focusing on those who had not received the COVID-19 vaccine and expressed hesitancy towards it. Convenience sampling was used to select the study participants, and formal in-depth virtual interviews were conducted on a one-to-one basis, employing a semi-structured questionnaire to guide the discussions. The interviews were meticulously recorded and transcribed, following the principles of reflexive thematic analysis, to distill key insights from the participants' responses. The study's findings, derived from the perspectives of 25 participants, illuminated a complex tapestry of reasons underlying vaccine hesitancy in Trinidad and Tobago. Notably, prominent themes emerged, including fear, doubts regarding vaccine efficacy, a perceived inadequacy of information, a sense of susceptibility to the virus, deep-seated mistrust, alternative herbal remedies, and religious reservations. Interestingly, the motivations expressed by these vaccine-hesitant individuals for potentially receiving the vaccine in the future were rooted in notions of necessity, an increased sense of susceptibility to the virus, a desire to reach a certain health benchmark, and a need for assurance regarding the vaccine's safety and effectiveness. This comprehensive exploration of vaccine hesitancy in TT provides valuable insights for public health officials and policymakers in crafting targeted strategies to address this critical issue within the local context. Conclusion: The findings of this study determined that vaccination against the SARS-CoV2 virus provided beneficial outcomes against infection, Covid-19 related hospitalizations, ICU admissions and mortality. While vaccination was deemed highly appropriate in managing the spread of the SARS-CoV2 virus and enhancing the outcomes in infected persons, the effectiveness of the different vaccine platforms indicated that certain vaccine platforms are preferential to others in different populations. In terms of vaccine efficacy, nucleic acid vaccines such as Pfizer-BioNTech and Moderna showed the greatest effectiveness while inactivated whole virus vaccines such as Sinopharm and viral vectors like Janssen had the least effectiveness. The side effects, joint/muscle soreness, pain at the injection site, shoulder pain, headaches, fever, chills, weakness, epistaxis, renal and certain cardiovascular events were common for all vaccine types. Adverse effects were more frequent and severe with the mRNA vaccines by Pfizer-BioNTech and Oxford-Astrazeneca than inactivated whole virus vaccines. The data collected in this research can be very useful to help individuals make a decision on which vaccine would be appropriate for them. More long-term studies are needed to better gauge the scope of side effects for each vaccine type.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

Little is known about the long-term durability of the induced immune response in subjects af-fected by obesity, particularly in those with an abdominal distribution of adipose tissue. We evaluated SARS-CoV-2-specific antibody response after BNT162b2 vaccine booster dose, com-paring individuals with abdominal obesity (AO) with those without, discerning between indi-viduals previously infected or not. IgG-TrimericS were measured in 511 subjects at baseline, 21 days after vaccine dose-1 and at one, three, six and nine months after dose-2 and at one and three months after booster dose. Nucleocapsid antibodies were assessed at baseline and at the end of the study to detect SARS-CoV-2 infection. To evaluate the three-months difference in absolute variation of IgG-TrmicericS levels from booster dose we used multivariable linear regression that showed interaction between AO and SARS-CoV-2 infection status (p=0.016). AO is associated with higher absolute IgG-TrimericS variation in prior infected individuals, regardless of possi-ble confounders and IgG-TrimericS levels at booster dose (p=0.0125). No interaction was evinced using BMI in the same regression model (p=0.418). The robust response in the development of antibodies after booster dose, observed in people with OA and previous infection, may support the recommendations to undergo the booster dose also in this population group.

Measles remains a highly contagious and potentially severe infectious disease, necessitating high vaccine coverage. However, misinformation and measles vaccine hesitancy/resistance posed significant challenges to achieving this goal. The COVID-19 pandemic further exacerbated these challenges, leading to a measles outbreak in Jordan in 2023. This study aimed to investigate the acceptance of the Measles-Rubella (MR) vaccine among parents in Jordan and identify its associated determinants. This cross-sectional questionnaire-based study was conducted using a previously Arabic-validated version of the Parental Attitudes towards Childhood Vaccines (PACV) survey instrument. Data collection took place in October 2023, and the final study sample comprised a total of 391 parents, with mothers representing 69.8% of the participants (n = 273). The majority of participating parents expressed either resistance (n = 169, 43.2%) or hesitancy (n = 168, 43.0%) towards MR vaccination, while only 54 participants (13.8%) expressed MR vaccine acceptance. Multivariate analysis revealed that trust in vaccine safety/efficacy, behavior, and having fewer offspring were significantly associated with MR vaccine acceptance. The current study revealed a concerning level of MR vaccine hesitancy/resistance among parents in Jordan. Urgent and targeted interventions are strongly recommended to address this issue, including mass campaigns aimed at building trust in the MR vaccine safety/efficacy. Additionally, there is an urgent need for effective public health initiatives to ensure sufficient measles vaccine coverage to prevent future outbreaks of this serious disease.

COVID-19, a contagious disease caused by the novel coronavirus SARS-CoV-2, emerged in 2019 and quickly became a pandemic, infecting more than 700 million people worldwide. The disease incidence, morbidity and mortality rates have started to decline since the development of effective vaccines against the virus and the widespread immunization of the population. SARS-CoV-2 vaccines are associated with minor local or systemic adverse reactions, while serious adverse effects are rare. Thyroid-related disorders have been reported after vaccination for COVID-19, and Graves’ disease (GD) is the second most common amongst them. Thyroid eye disease (TED), an extrathyroidal manifestation of GD is rarely observed post COVID-19 vaccination. All TED cases followed mRNA-based vaccinations, but two new onset mild TED cases post viral vector vaccine (ChAdox1nCoV-19) have also been reported. We report the case of a 63-year-old woman who presented with new onset hyperthyroidism and moderate-to-severe and active TED ten days after she received the first dose of a viral vector vaccine against SARS-CoV-2. This is the first case of moderate-to-severe TED after such a vaccine. Our patient was initially treated with intravenous glucocorticoids and subsequently with intravenous rituximab, due to no response. The disease was rendered inactive after rituximab, but constant diplopia persisted, and the patient was referred for rehabilitative surgery.

ABSTRACT: Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neurooncology, and the survival status of patients after relapse usually means rapid deterioration, and also the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulate the body's immune system to recognize and attack cancer cells , which could be used as a in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma, This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and focus on the rGBM especially.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOC) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5,007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOC, including Alpha (n =714), Delta (n =1,877), and Omicron (n =1,802). Omicron isolates were further sub-typed as BA.1 (n =899), BA.2 (n =853), and BA.4/BA.5 (n =50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1,577/5,007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p &lt;0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p &lt;0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p &lt;0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

World Health Organization (WHO) has announced the monkeypox (MPX) epidemic a global public health emergency due to its re-emergence, remarkable increase in the number of MPX cases worldwide, and its potential spread. This paper introduces the symptoms, complications, and features of MPX; its transmission, diagnosis and testing, vaccines and treatment; MPX and sexually transmitted diseases, especially the human immunodeficiency virus (HIV); possible natural hosts or reservoirs of the monkeypox virus (MPXV). A useful tool for MPX and surgical safety recommendations are presented. The challenges in fighting the MPX epidemic, One Health strategy, and future research are discussed.

FMD is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are used to induce an immune response, but it is not sufficient to show the effect of preventing viral infection. In this study, we conducted to evaluate the increasing effect of FMD vaccine SP antibody by administrating Zn-ASP to 100 pigs from three test pig farms with feed. FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of FMD vaccine SP antibody in the 0.2% Zn-ASP-administered group significantly increased compared to that in the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8 and 16 weeks after the second vaccination, respectively (p&lt;0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. IFN-γ and IgA were significantly increased by Zn-ASP administration 4 weeks after the first vaccination and 4 weeks after the second vaccination (p&lt;0.05). On the other hand, serum AST, and CPK (p&lt;0.001) were significantly decreased by Zn-ASP. Our results show that the administration of Zn-ASP is effective in enhancing the antibody titer and immunity of the FMD vaccine by FMD vaccination, and it is thought that it can be used as an oral adjuvant (OrAd) to prevent viral diseases such as FMD.

The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we report the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and correctly processed and transported to the cell surface, where it efficiently produced cell-cell fusion. Version Spf, however, was not proteolytically processed and despite being transported to the plasma membrane, it failed to induce cell-cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin converting enzyme 2 (K18-hACE2) mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the levels of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine

Coronavirus disease (COVID-19) has had devastating impacts on the global economy and public health. This study aimed to assess the level of COVID-19 vaccine acceptance, hesitancy, and associated factors among staff and students of the Federal University of Health Sciences Otukpo, Benue State, Nigeria. A web-based cross-sectional survey was conducted between November 2021 and April 2022, and data were collected and analyzed using descriptive and inferential statistics. Of the 150 completed and analyzed questionnaires, the majority of respondents (80.0%) were between 16 and 45 years old. The study found that 58.4% of participants indicated vaccine hesitancy, with skepticism about the vaccine's fast production/rollout and fear of vaccine side effects being the most common reasons for hesitation. Respondents' age, religion, and category were significant factors influencing vaccine acceptance and hesitancy (P < 0.05). The university community has a high level of awareness of COVID-19 but low vaccine acceptance, resulting in high levels of vaccine hesitancy. The study recommends that policymakers and public health officials should prioritize testing and vaccination for job categories with higher risk of exposure to COVID-19. They should provide accurate information about COVID-19 testing and vaccination and implement workplace-based testing and vaccination programs. These interventions can help to increase COVID-19 testing and vaccination uptake among the university community and mitigate the spread of COVID-19.

Cervical cancer is preventable through vaccination, early detection, and treatment of precancerous lesions. However, global inequalities mean that the disease remains a leading cause of cancer death around the world, with over 80% of new cases and 90% of deaths occurring in low and middle-income countries (LMICs). In El Salvador, joint efforts between the Ministry of Health (MoH) and the non-profit organization Basic Health International (BHI) have been in place since 2008 with the goal of reducing the country’s disease burden. While the World Health Organization’s (WHO) call to action to eliminate cervical cancer provided worldwide momentum to implement new public health initiatives, the COVID-19 pandemic disrupted ongoing programs and jeopardized plans for the future. The purpose of this manuscript is to describe the progress that El Salvador has achieved in improving cervical cancer prevention, the impact of the pandemic on current strategies, and potential solutions that can help the country meet the WHO’s strategic targets by 2030 to accelerate the elimination of cervical cancer.

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

There exists a compelling need to better understand the temporal dynamics of public sentiment towards COVID-19 vaccines in the US on a national and state-wise level for facilitating appropriate public policy applications. Our analysis of social media data from early February of 2021 and late March of 2021 shows that in spite of overall strength of positive sentiment, and increasing numbers of Americans being fully vaccinated, negative sentiment about COVID-19 vaccines still persists among sections of people who are hesitant towards the vaccine. In this study, we performed sentiment analytics on vaccine tweets, studied changes in public sentiment over time, conducted vaccination sentiment validation using actual vaccination data from the US CDC and Household Pulse Survey (HPS), explored influence of maturity of Twitter user-accounts and generated geographic mapping of sentiments by location of Twitter users. Furthermore, we leverage the emotion polarity based Public Sentiment Scenarios (PSS) framework which was developed for COVID-19 sentiment analytics, to systematically analyze directions for public policy processes to potentially improve the administration of vaccines. Application of the PSS framework provides important time sensitive insights for state and federal government agencies and associated organizations to better implement public policy processes for healthcare management, communication, transparency, motivation and societal operational policies such as social distancing. These insights are expected to contribute to processes that can expedite the vaccination program and move closer to the cherished herd immunity goal.

The novel coronavirus (COVID-19) was first reported in the U.S. on December 29, 2019 and has spread rapidly throughout the country, affecting individuals with varying severity due to their risk status. According to the Centers for Disease Control and Prevention, it is estimated that 45.4% of US adults are at higher risk for complications from coronavirus disease because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. In this study, we developed a mathematical model to assess the impact of a COVID-19 vaccine among low and high risk groups. Numerical simulations shows vaccinating both low and high risk groups simultaneously, rather than prioritizing the vaccine on high risk group only, further reduces the daily mortality. The result supports the need for an aggressive vaccination program, regardless of whether individuals are within the low or high risk population.

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shape nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a non-coding ssRNA template. The PapMV nanoparticle induces innate immunity through stimulation of the toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, either at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the CTL epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C) using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate the TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.

Healthy human subjects develop spontaneous CD8+ T cell responses to melanocyte antigens (MA) expressed by normal melanocytes, such as Tyrosinase, MAGE-A3, Melan/Mart-1, gp100, and NY-ESO-1. This natural autoimmunity directed against melanocytes might confer protection against the development of malignant melanoma (MM), where MA are present as overexpressed tumor-associated antigens. Consistent with this notion we report here that functional T cell reactivity to MA was found to be diminished in untreated MM patients: while 57.5% of healthy controls (n=40) exhibited high-frequency MA-specific T cell reactivity ex vivo, such was detected in only 12% of the untreated MM patients (n=24). Three lines of evidence suggest that the MA-reactive T cells present in healthy subjects undergo exhaustion once MM establishes itself. First, only the MA-specific T cell reactivity was affected in the MM patients; that to third party recall antigens was not. Second, in these patients, the residual MA-specific T cells, unlike third party antigen reactive T cells, were functionally impaired, showing a diminished per cell IFN-γ productivity. Third, successful immunotherapy with AGI-101H melanoma vaccine restored natural CD8+ T cell autoimmunity to MA in 85% of the vaccinated patients (n= 27). The role of natural T cell autoimmunity to tumor-associated MA is discussed based on discrete levels of T cell activation thresholds.

Global severity maps of ongoing dengue epidemic and COVID-19 pandemic do not overlap. Countries with high dengue endemicity (>1.5 million cases/year) are observably less hit by COVID-19 in terms of infection, transmission and mortality. Based on non-overlap of dengue and COVID-19 severity maps and evidence of SARS-CoV-2 serological cross-reactions with dengue, we wonder whether immediate immunization of susceptible populations in Europe, North America and Asia (China, Iran) with available live-attenuated dengue vaccines, will cue the anti-viral immune response to thwart COVID-19 (viral interference). Risk of developing post-vaccination “Antibody-dependent Enhancement” is low as dengue is not endemic in the aforesaid regions.

A B S T R A C T Genital herpes disease is caused mainly by herpes simplex virus type 2 (HSV-2), which is sexually transmitted with a high prevalence in both developed and developing countries. No vaccine is currently available against genital herpes. In this study, we introduced and expressed two genes encoding HSV-2 glycoprotein D (gD) and VP16 protein and a GFP marker gene (control) in tobacco seedlings. Positive plant infection was assessed through characteristic tobacco mosaic virus disease symptoms on leaves and by monitoring the fluorescence emitted by the expressed GFP protein. Expression of the HSV-gD2 and VP16 antigens was verified by RT-PCR, ELISA and Western blot. As a proof of concept, the immunogenicity and the protection ability of the plant produced gD antigen was tested in a mouse model of genital herpes and compared to gD antigen produced in a mammalian expression system. This showed that the plant-gD preparation, when used in combination with a CpG oligodeoxynucleotide as adjuvant, was highly immunogenic and capable of inducing complete immunity to lethal vaginal HSV-2 challenge in mice. Thus, the data presented here may have implications for the development of a production system for highly immunogenic plant-based HSV-2 vaccine antigens.

Models of subsurface structures are important for successful deposit exploration but are challenged by the need to integrate data from different geophysical methods. In the present study, we evaluated a method of joint inversion in which audio-magnetotelluric (AMT) and dual frequency induced polarization (DFIP) data sets are inverted simultaneously to produce a consistent 2D resistivity model to show a clear image of subsurface structures. To achieve the objectives, we conducted AMT and DFIP surveys first on the same survey line within the Dongjun lead-zinc deposit in inner Mongolia by developing 31 AMT survey sites with an interstation separation of 40 m on a 1440 m survey track and operated in fifty-three frequencies in the range 1–10,400 Hz to record the resistivity distribution of subsurface to depths exceeding 800 m. The same survey setup up was applied to the DFIP method by utilizing the SQ-3C model with a pole-dipole array configuration and conducted measurements at frequencies of 4 Hz and 4/13 Hz. We first separately inverted AMT and DFIP measurements. The two-dimensional (2D) model obtained from AMT data revealed distinct low resistivity anomalies in the middle of the 2D inversion model. In contrast, the DFIP inversion model showed a high resistive body in the same region. In response to the discrepancies observed in the separate 2D inversion models, we implemented a joint inversion for both the AMT and DFIP datasets. The joint inversion resistivity model shows surficial conducting bodies and a high conductive body along the profile with relatively high Percent Frequency Effect (PEF) indicating high chargeability. The final joint inversion resistivity model clearly images the large silica alteration zone and the Pb-Zn mineralization. This study demonstrates the feasibility of a joint inversion methodology and highlights the value of integrating geophysical methods through joint inversion for enhanced characterization and exploration of lead-zinc ores.

Secondary movement disorders (SMDs) represent a heterogeneous group of neurological conditions characterized by abnormal, involuntary movements resulting from various underlying causes. This comprehensive review aims to thoroughly understand SMDs, including their epidemiology, pathophysiology, clinical manifestations, diagnostic approach, and management strategies. SMDs encompass a spectrum of movement abnormalities, including dystonia, chorea, athetosis, myoclonus, tics, and tremors. They can arise from a multitude of etiologies, such as drug-induced effects, post-infectious processes, metabolic disturbances, and structural brain lesions. The epidemiology of SMDs varies depending on the underlying cause, with some conditions being more prevalent in specific populations or age groups. Understanding the pathophysiology of SMDs is crucial for accurate diagnosis and targeted management. Diagnosing SMDs requires a comprehensive approach, including a detailed history, physical examination, laboratory investigations, neuroimaging studies, and sometimes electrophysiological studies. Management of SMDs is multifaceted and may involve pharmacological, non-pharmacological, and surgical interventions. Individualized treatment plans are essential, considering the underlying cause, severity of symptoms, and patient preferences. Emerging concepts in the field of SMDs include advancements in genetic research, identification of biomarkers, and development of novel therapeutic approaches. There is a growing focus on patient-centered care and improving the quality of life for individuals with SMDs. In conclusion, SMDs pose diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management. Continued research and collaboration are essential for advancing our understanding and treatment of these complex disorders.

The role of initial state (ISI) and final state (FSI) ion–ion interactions in heavy ion double charge exchange (DCE) reactions A(Z,N)→A(Z±2,N∓2) are studied in the context of double single charge exchange (DSCE) reactions given by sequential actions of the isovector nucleon–nucleon (NN) T–matrix. The second order DSCE reaction amplitude is investigated in momentum representation in a formulation, focused on the extraction of nuclear matrix elements under the conditions of strong initial state (ISI) and final state (FSI) interactions. In closure approximation and using the momentum representation, the reaction amplitude is finally separated into ISI/FSI distortion coefficients and reaction kernels and nuclear matrix elements. The ISI/FSI reaction kernels emerge as the result of the repeated scattering on the avoided volume, introduced by the imaginary parts of the ion–ion optical potential and acting as sinks for the quantal probability current. The closure approximation allows derive a set of induced effective two–body isotensor interactions, given by products of spin–scalar, spin–vector central and rank–2 spin–tensor interactions. The intermediate propagator plays a key role in establishing correlation between the DCE transitions in the projectile and target nucleus. The presented approach emphasizes the special features of DSCE reaction dynamics as proceeding like a system of two coupled isospin dipoles whose strengths are determined by the momentum-space form factors of the NN isovector interaction. The properties of the DSCE interaction form factors are investigated and the approach is applied to data.

Two pre-pulses focused at different positions and at different time moments were used to enhance THz emission generated by the main pulse. The emission of THz radiation from air breakdown regions of focused ultrashort fs-laser pulses (800 nm/35 fs) at shockwave front prepared by pre-pulses was investigated, and a 3D spatio-temporal control was established for the most intense emission. The laser pulse-induced air breakdown forms a ~120 micrometers-long focal volume and generates a shockwave that delivers denser air into the focal region of the main pulse for enhanced generation of THz radiation at 0.1-2.5 THz spectral window. The intensity of pre- and main-pulses was at the tunneling ionisation intensities (1-3)x10¹⁶ W/cm² and corresponded to sub-critical (transparent) plasma in air. Polarisation analysis revealed that the orientation of the air density gradients generated by pre-pulses and their time-space placement defined the ellipticity of the generated THz electrical field. The rotational electric current is the origin of THz radiation. The current is created by non-parallel gradients of electron density and temperature. Scaling dependencies of THz emission control are established.

ABSTRACT: Iodixanol is an iso-osmolar nonionic dimeric hydrophilic contrast agent with a higher viscosity than the monomeric agents. It is the only Food and Drug Administration (FDA)approved isoosmolar agent in the United States, and it is the only contrast agent with an FDA-approved indication for use in cardiac computed tomographic angiography (CCTA), to assist in the diagnostic evaluation of patients with suspected coronary artery disease. In clinical studies, it has been noted to have fewer side effects and similar image quality when compared to low osmolar contrast media. This can be attributed to the pharmacological properties of iodixanol. In the field of cardiology, iodixanol among other intravenous contrast media is used for coronary computed tomography angiography and cardiac catheterization. In this article, the use, tolerability and efficacy of iodixanol in the field of cardiology are reviewed, specifically evaluating the use for CCTA and coronary angiography, including outcome studies, randomized trials and comparisons to other contrast agents.

In this study, we considered the structural stability, electronic properties, and phonon dispersion of the cubic (c-ZrO₂), tetragonal (t-ZrO₂), and monoclinic (m-ZrO₂) phases of ZrO₂. We found that the monoclinic phase of zirconium dioxide is the most stable among the three phases in terms of total energy, lowest enthalpy, highest entropy, and other thermodynamic properties. The smallest negative modes were found for m-ZrO₂. Our analysis of the electronic properties showed that during the m–t phase transformation of ZrO₂, the Fermi level first shifts by 0.125 eV toward higher energies and then decreases by 0.08 eV in the t–c cross-section. The band gaps for c-ZrO₂, t-ZrO₂, and m-ZrO₂ are 5.140 eV, 5.898 eV, and 5.288 eV, respectively. Calculations based on the analysis of the influence of doping 3.23, 6.67, 10.35, and 16.15 mol. %Y₂O₃ onto the m-ZrO₂ structure showed that the enthalpy of m-YSZ decreases linearly, which accompanies further stabilization of monoclinic ZrO₂ and an increase in its defectiveness. A doping-induced and concentration-dependent phase transition in ZrO₂ under the influence of Y₂O₃ was discovered, due to which the position of the Fermi level changes and the energy gap decreases. It has been established that, not only for pure systems but including those doped with Y₂O₃, the main contribution to the formation of the conduction band is made by the p-states of electrons. The t-ZrO₂ (101) and t-YSZ (101) surface models were selected as optimal surfaces for water adsorption based on a comparison of their surface energies. An analysis of the mechanism of water adsorption on the surface of t-ZrO₂ (101) and t-YSZ (101) showed that H₂O on unstabilized t-ZrO₂ (101) is adsorbed dissociatively with an energy of -1.22 eV, as well as by the method of molecular chemisorption with an energy of - 0.69 eV and the formation of a hydrogen bond with a bond length of 1.01 Å. In the case of t-YSZ (101), water is molecularly adsorbed onto the surface with an energy of -1.84 eV. Dissociative adsorption of water occurs at an energy of -1.23 eV, near the yttrium atom. The results show that ab initio approaches are able to describe the mechanism of doping-induced phase transitions in (ZrO₂+Y₂O₃)-like systems, based on which it can be assumed that DFT calculations can also flawlessly evaluate other physical and chemical properties of YSZ, which have not yet been studied quantum chemical research. The obtained results complement the database of research works carried out in the field of the application of biocompatible zirconium dioxide crystals and ceramics in green energy generation and can be used in designing humidity-to-electricity converters and creating solid oxide fuel cells based on ZrO₂.

In this study, we considered the structural stability, electronic properties, and phonon dispersion of the cubic (c-ZrO₂), tetragonal (t-ZrO₂), and monoclinic (m-ZrO₂) phases of ZrO₂. We found that the monoclinic phase of zirconium dioxide is the most stable among the three phases in terms of total energy, lowest enthalpy, highest entropy, and other thermodynamic properties. The smallest negative modes were found for m-ZrO₂. Our analysis of the electronic properties showed that during the m–t phase transformation of ZrO₂, the Fermi level first shifts by 0.125 eV toward higher energies and then decreases by 0.08 eV in the t–c cross-section. The band gaps for c-ZrO₂, t-ZrO₂, and m-ZrO₂ are 5.140 eV, 5.898 eV, and 5.288 eV, respectively. Calculations based on the analysis of the influence of doping 3.23, 6.67, 10.35, and 16.15 mol. %Y₂O₃ onto the m-ZrO₂ structure showed that the enthalpy of m-YSZ decreases linearly, which accompanies further stabilization of monoclinic ZrO₂ and an increase in its defectiveness. In this case, the position of the Fermi level changes abruptly, and the energy gap decreases. It has been established that, not only for pure systems but including those doped with Y₂O₃, the main contribution to the formation of the conduction band is made by the p-states of electrons. The t-ZrO₂ (101) and t-YSZ (101) surface models were selected as optimal surfaces for water adsorption based on a comparison of their surface energies. An analysis of the mechanism of water adsorption on the surface of t-ZrO₂ (101) and t-YSZ (101) showed that H₂O on unstabilized t-ZrO₂ (101) is adsorbed dissociatively with an energy of -1.22 eV, as well as by the method of molecular chemisorption with an energy of - 0.69 eV and the formation of a hydrogen bond with a bond length of 1.01 Å. In the case of t-YSZ (101), water is molecularly adsorbed onto the surface with an energy of -1.84 eV. Dissociative adsorption of water occurs at an energy of -1.23 eV, near the yttrium atom. The obtained results complement the database of research works carried out in the field of the application of biocompatible zirconium dioxide crystals and ceramics in green energy generation and can be used in designing humidity-to-electricity converters and creating solid oxide fuel cells based on ZrO₂.

Differentiation of induced pluripotent stem cells to a range of useful, mature target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, organoids expressed ACE2 capable of binding SARS-Cov2 spike protein demonstrating the physiological relevance of the organoids produced. This study demonstrates the rapid production of pulmonary organoids using a multi-germ layer approach that could be used for studying novel respiratory disease interactions.

This work discusses diatomic molecular spectroscopy of laser-induced plasma and analysis of data records, specifically signatures of cyanide, CN. Line strength data from various databases are compared for simulation of the CN, B2Σ+⟶X2Σ+, Δv=0 sequence. Of interest are recent predictions using an astrophysical database, i.e., ExoMol, a laser-induced fluorescence database, i.e., LIFBASE, and a program for simulating rotational, vibrational and electronic spectra, i.e., PGOPHER. Cyanide spectra that are predicted from these databases are compared with line strength data that are in use by the author for the last three decades in the analysis of laser-plasma emission spectra. Comparisons with experimental laser-plasma records are communicated as well, and for spectral resolutions of 33 and 110 picometer. The accuracy of the CN line strength data is better than one picometer. Laboratory experiments utilize 308-nm, 35-picosecond bursts within an overall 1-nanosecond pulse-width, and 1064-nm, 6-ns pulse-width radiation. Experimental results are compared with predictions. Differences of the databases are elaborated for equilibrium of rotational and vibrational modes and at an internal, molecular temperature of the order of 8,000 Kelvin. Applications of accurate CN data include for example combustion diagnosis, chemistry, and supersonic and hypersonic expansion diagnosis. The cyanide molecule is also of interest in the study of astrophysical phenomena.

Objectives: Although pitch reception poses a great challenge for individuals with cochlear implants (CIs), formal auditory training (e.g., high variability phonetic training, HVPT) has been shown to provide direct benefits in pitch-related perceptual performances such as lexical tone recognition for CI users. As lexical tones in spoken language are expressed with a multitude of distinct spectral, temporal, and intensity cues, it is important to determine the sources of training benefits for CI users. The purpose of the present study was to conduct a rigorous fine-scale evaluation with the categorical perception (CP) paradigm to control the acoustic parameters and test the efficacy and sustainability of HVPT for Mandarin-speaking pediatric CI recipients. The main hypothesis was that HVPT-induced perceptual learning would greatly enhance CI users’ ability to extract the primary pitch contours from spoken words for lexical tone identification and discrimination. Furthermore, individual differences in immediate and long-term gains from training would likely be attributable to baseline performance and duration of CI use. Design: Twenty-eight prelingually deaf Mandarin-speaking kindergarteners with CIs were tested. Half of them received five sessions of HVPT within a period of three weeks. The other half served as control who did not receive the formal training. Two classical CP tasks on a tonal continuum from Mandarin Tone 1 (high-flat in pitch) to Tone 2 (mid-rising in pitch) with fixed acoustic features of duration and intensity were administered before (pretest), immediately after (posttest), and 10 weeks post training termination (follow-up test). Participants were instructed to either label a speech stimulus along the continuum (i.e., identification task) or determine whether a pair of stimuli separated by zero or two steps from the continuum was the same or different (i.e., discrimination task). Identification function measures (i.e., boundary position and boundary width) and discrimination function scores (i.e., between-category score, within-category score, and peakedness score) were assessed for each child participant across the three test sessions.Results: Linear mixed-effects (LME) models showed significant training-induced enhancement in lexical tone categorization with significantly narrower boundary width and better between-category discrimination in the immediate posttest over pretest for the trainees. Furthermore, training-induced gains were reliably retained in the follow-up test 10 weeks after training. By contrast, no significant changes were found in the control group across sessions. Regression analysis confirmed that baseline performance (i.e., boundary width in the pretest session) and duration of CI use were significant predictors for the magnitude of training-induced benefits. Conclusions: The stringent CP tests with synthesized stimuli that excluded acoustic cues other than the pitch contour and were never used in training showed strong evidence for the efficacy of HVPT in yielding immediate and sustained improvement in lexical tone categorization for Mandarin-speaking children with CIs. The training results and individual differences have remarkable implications for developing personalized computer-based short-term HVPT protocols that may have sustainable long-term benefits for aural rehabilitation in this clinical population.

Disruptive technologies (DT) have featured prominently in almost every human activity since the advent of computerization. The likely effects of DT on economic processes and human professions have and continue to generate fears and debates which spurred this investigation. To break away from the traditional approach the operational breakeven theory and the discriminant analysis techniques of Altman’s Z-score, and Enyi’s Relative Solvency Ratio were used to examine the relationship between firms’ market-induced-survival-ratio (MISR) and the disruptive technology gains index (DTGI) of seventy-three firms drawn from Nigeria and India. Descriptive and inferential statistics were used to analyze the data generated. The results showed that a sizeable number of firms has profited from the introduction of disruptive technologies with MISR and DTGI returning a 10% significant relationship while others are still struggling to measure up to the requirements of disruptive technologies in their chosen economic fields. The implication of this is that businesses must brace up and embrace digital transformation if they must stay afloat in this era of disruptive technologies. This study recommends a revolutionary approach to digital transformation in view of the fast pace of global integration while managers and business owners should adopt more pragmatic approach in appraising the operations and finances of a firm for effective results and timely responses to potential business challenges.

Geomagnetic induced current (GIC) is a ground end manifestation associated with the space weather perturbations that should be greatly taken into account by the society. Although the GICs implication to the power system is not regular, it can cause large scale of system failure. In equatorial, the power system is considered safe since the most intense of geomagnetic storm happened in high latitude. However, the internal damage due to GICs which finally led to the South African power system failure has totally changed the normal perception. Therefore, a preliminary investigation on the GICs activity in equatorial region is performed to understand the space weather impact to the power system. Time derivative of the horizontal magnetic field component (dB/dt) is done to indicate the GICs activity value based on Faraday’s law. All the reported power failures are compiled to produce the threshold value of dB/dt, which possibly cause the harmful effect to the system. Then, dB/dt analysis is extended to show the pattern of GICs activity in function of magnetic latitude and local time. The results reveal that power network in equatorial region has possibly suffered by GIC. Plus, high number of intense GIC activity in this region occurred during dayside.

This article reports new measurements of laser-induced plasma hypersonic expansion measurements of diatomic molecular cyanide (CN). Focused, high-peak power 1064-nm Q-switched radiation of the order of 1 TW/cm² generates optical breakdown plasma in a cell containing a 1:1 molar gas mixture of N₂ and CO₂ at a fixed pressure of 1.1 × 10⁵ Pascal and in a 100 ml/min flow of the mixture. Line-of-sight (LOS) analysis of recorded molecular spectra indicate the outgoing shockwave at expansion speeds well in excess of Mach number 5. Spectra of atomic carbon confirm an increased electron density near the shock wave, and equally, molecular CN spectra reveal higher excitation temperature near the shockwave. The results are consistent with corresponding high-speed shadow graphs obtained by visualization with an effective shutter speed of five n anosecond. In addition, LOS analysis and application of integral inversion techniques allow inferences about the spatio-temporal distribution of the plasma.

Laser-induced breakdown spectroscopy (LIBS) of pharmaceutical drugs that contain paracetamol is investigated in air and argon atmospheres. Characteristic neutral and ionic spectral lines of various elements and molecular signatures of CN violet and C₂ Swan band systems are observed. The relative hardness of all drug samples is measured as well. Principal component analysis, a multivariate method, is applied in data analysis for demarcation purposes of the drug samples. The CN violet and C₂ Swan spectral radiances are investigated for evaluation of possible correlation of the chemical and molecular structures of the pharmaceuticals. Complementary Raman and Fourier-transform-infra-red spectroscopies are used record molecular spectra of the drug samples. The applicationof the above techniques for the drug screening are important for identification and mitigation of drugs that reveal additives that may cause adverse side-effects.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Respiratory Syncytial Virus (RSV) continues to pose a significant challenge, contributing to elevated hospitalization rates among children up to 5 years old, with a disproportionate burden on newborn and infants under 6 months old. The unique characteristics of the young immune system make it prone to altered responses to infections and vaccinations, requiring a tailored approach to disease prevention. The recent approval of the maternal RSV vaccine, (brand name ABRYSVO), represents a pivotal advancement in preventive strategies among newborns and infants, marking a milestone in RSV research as the first market-approved maternal vaccine. The present review examines clinical trial data on both recent and previous vaccine candidates, as well as the licensed vaccine, focusing on the prevention of RSV disease in newborns and young infants through the passive acquisition of antibodies following maternal immunization. Additionally, it evaluates the safety profile of these vaccines.

In Nigeria, Cervical cancer (CC) and lack of Human Papillomavirus (HPV) awareness poses significant HPV infection risk among women. This study was conducted at Ibrahim Badamasi Babangida (IBB) University in Nigeria; focused on assessing HPV awareness and knowledge, particularly concerning its association with CC and oral contraceptive (OC) pills among students and staff. We adapted and validated a 20-item HPV knowledge scale and explored factors influencing knowledge, vaccination rates, awareness, and the impact of ethnicity on HPV knowledge. Also, due to the non-normality of the knowledge score, non-parametric tests were done. Data were summarized using median and interquartile range (IQR), while categorical data were presented in frequency and percentage distribution. We established the reliability of the 20-item knowledge scale with a strong Cronbach's alpha coefficient of 0.913, indicating internal consistency. However, it revealed a concerning lack of awareness and knowledge about HPV, only 34.8% of participants were aware of HPV infection, and only 25.0% knew about HPV vaccine. Additionally, ethnicity was identified as a significant factor affecting HPV knowledge. Considering these findings, this study emphasizes the need for targeted interventions to enhance HPV awareness and knowledge, particularly among specific ethnic groups. Despite the development and validation of a reliable knowledge scale, the study underscores the importance of educational initiatives to address this knowledge gap, ultimately reducing the risk of HPV infection and CC in Nigeria.

More than 13.5 billion COVID-19 vaccine doses have so far been delivered between 2021 and 2023 through a mix of delivery platforms, with mass vaccination campaigns being the main approach. In 2022, with the most likely scenario of continued circulation of SARS-CoV-2 and the need for periodic booster doses, there was a need for countries to plan for more sustainable approaches to provide COVID-19 vaccination. In this context of uncertainty, a global tool for integrating COVID-19 vaccines into immunization programmes and primary health care was published jointly by WHO and UNICEF to respond to country needs. The guidance leveraged existing health system frameworks, proposed four steps for the COVID-19 integration journey, and identified investment areas. The development process maximized robust global stakeholder and country engagement, and the timeframe was aligned with donor funding windows to support the integration of COVID-19 vaccination. The rapid dissemination of guidance allowed its use by countries to ascertain their readiness for integrating COVID-19 vaccination and inform the development of national plans and funding applications. While progress has been made in specific areas (e.g., optimizing cold chain and logistics leveraging COVID-19 vaccination), in the context of decreasing demand for COVID-19 vaccines, reaching adult COVID-19 vaccine high-priority-use groups and engaging and coordinating with other health programmes (beyond immunization) remains a challenge. We share the learning that despite the uncertainties of a pandemic, guidance documents can be developed and used within a short timeframe. Working in partnership with stakeholders beyond immunization towards a common objective is powerful and can allow progress to be made on integrating health services and preparing better for future pandemics.

Neisseria meningitidis (N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and machine learning methods, we estimated the potential strain coverage by fHbp and NHBA vaccine variants (51 and about 30%, respectively); the NadA antigen sequence was found in only 17.8% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden coverage of N. meningitidis strains.

During the COVID-19 pandemic, online media were the most widely used source of scientific information. Often, they are also the only ones on science-related topics. Research has shown that much of the information available on the Internet about the health crisis lacked scientific rigor and that misinformation about health issues can pose a threat to public health. In turn, millions of Catholics were found to be demonstrating against vaccination against COVID-19 based on "false" and misleading religious arguments. This research analyses publications about the vaccine in Catholic online media with the aim of understanding the presence of information (and misinformation) in this community. An algorithm designed for each media outlet collected COVID-19 vaccine-related publications from 109 Catholic media outlets in five languages. In total, 970 publications were analysed for journalistic genres, types of headlines and sources of information. The results show that most publications are informative and most of their headlines are neutral. However, opinion articles have mostly negative headlines. Also, a higher percentage of the opinion authors come from the religious sphere and most of the sources cited are religious. Finally, 35% of the publications relate the vaccine to the framing issue of abortion.

The most widely spread and neglected zoonotic disease – Leptospirosis, with an estimated 1.03 million cases and 58,900 deaths occurring annually, is a concern and can be prevented only by effective immunization. Due to the urgent need for a novel vaccine, various research organizations have been evaluating the protective immune response elicited by recombinant vaccines. In this study amino-acid sequences of Outermembrane protein (OMPL) 1, LipL 32, 41 and 46 from ten pathogenic serovars of Leptospira were selected to obtain epitopes that induce CD4+ and CD8+ T cell responses by binding to the MHC molecules. These B cell and T cell epitopes were used to design multi-epitope vaccine to which an adjuvant sequence was added at the N-terminal end and appropriate linkers were used to join the different epitopes to increase the efficiency of the vaccine constructs. Using an immuno-informatics approach, constructs were analyzed for the physiochemical properties, secondary and tertiary structure and its validation, docking with different receptors and prediction of binding affinity for each docked complex, followed by molecular dynamics simulation. Taking in consideration all the results, multi-epitope constructs designed may prove to be promising vaccine candidates against Leptospirosis and warrants experimental validation.

Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain chimeric virus became neuroinvasive in doses of 107-106 PFU and can be used as a model of Flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.

Vaccination is one of the best approaches to control and eradicate foot-and-mouth disease (FMD). To achieve this goal, vaccines with inactivated FMD virus antigen in suitable adjuvants are being used in addition with other control measures. However, only a limited number of vaccine strains are commercially available which often have a restricted spectrum of activity against the different FMD virus strains in circulation. As a result, when new strains emerge, it is important to measure the efficacy of the current vaccine strains against these new variants. This is important for countries where FMD is endemic but also for countries that hold an FMD vaccine bank to be prepared for emergency vaccination. The emergence and spread of the O/ME-SA/Ind-2001 lineage of viruses posed a serious threat to countries which had OIE-endorsed FMD control plans and had not reported FMD for many years. In vitro vaccine matching results showed a poor match (r1-value &lt;0.3) to the more widely used vaccine strain O Manisa and less protection in a challenge test. This paper describes the use of O3039 vaccine strain as an alternative either alone or in combination with the O Manisa vaccine strain with virulent challenge by a O/ME-SA/Ind-2001d sub-lineage virus from Algeria (O/ALG/3/2014). The experiment included challenge at 7 days post vaccination (to study protection and emergency use) and 21 days post vaccination (as would be done in standard potency studies). The results indicated that the O3039 vaccine strain alone as well as the combination with O Manisa is effective against this strain of the O/ME-SA/Ind/2001d lineage offering protection from clinical disease even after 7 days post vaccination and with reduction in viraemia and virus excretion.

The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. 1,150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign.

Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) is the virus that caused COVID-19 around the world. The disease starts off as a flu-like symptom and then eventually spreads in the human body.Infections are easily transmitted from human to human which makes it more severe among individuals. SARS-CoV-2 virus is in the same family of viruses SARS and MERS.As of today, there is no approved vaccine that can cure COVID-19. However, potential treatments showing promising improvement results among affected COVID-19 patients. In this review, the effectiveness of the current treatments for COVID-19 has been explored.

New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat the COVID-19 disease. Several approaches are being used by scientists for investigation including 1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease and 2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, new B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries such as the Netherlands, Switzerland and France.

Influenza virus imprinting is now understood to significantly the influence immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year to subsequently build a complex influenza virus immune history but very little is known about how the imprinting strain influences vaccine responses. To investigate the imprinted host immune responses to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60 day recovery period was given to build immune memory, ferrets were immunized and the challenge at Day 123. Samples were collected throughout the time course and immunological assays were performed to investigate recall mechanisms. The preimmune-vaccinated ferrets did not experience significant disease during challenge while naïve-vaccinated ferrets had severe disease. Hemagglutination inhibition assays showed preimmune ferrets had a more robust antibody response post vaccination, increased virus neutralization activity. Virus specific immunoglobulins were of predominantly the IgG isotype suggesting B cell maturity and plasticity at vaccination. These results are important and should be considered for vaccine design.

Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the CDC recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic ,cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an ELISA and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.

The wealth of data obtained during the past 20 years using Laser-Induced Breakdown Spectroscopy (LIBS) indicates that the technique is very promising to detect small chemical contents of alloying elements. The potential of LIBS was looked more seriously during the past two decades or so as more data were obtained on Aluminum and steel to study the phenomena in the condition of local thermodynamic equilibrium and time-delay between a Q-switch laser and an intensified CCD camera. Since the past decade, some data on compounds were also shown to be useful in determining small concentrations of harmful elements. This manuscript is intended to show that the technique of LIBS performance is very promising in fields such as micro-machining, in alloying element analysis, surface cleaning and environmental applications even with lightweight spectrometers having a relatively low resolution, which can potentially be air-borne.

This work communicates analysis of aluminum monoxide, AlO, laser-plasma emission records using line strength data and the ExoMol astrophysical database. A nonlinear fitting program computes comparisons of measured and simulated diatomic molecular spectra. Predicted cyanide spectra of the AlO, ${\rm B}\ ^2\,\Sigma^+ \longrightarrow {\rm X} \ ^2\,\Sigma^+$, $\Delta {\rm v} = 0, \pm 1, \pm 2, + 3$ sequences and progressions compare nicely with 1 nanometer resolution experimental results. The analysis discusses experiment data captured during laser ablation of Al$_2$O$_3$ with 266-nm, 6-mJ pulses. The accuracy of the AlO line strength data is better than one picometer. This work presents as well comparison of the $^{27}$Al$^{16}$O line strength and of ExoMol data for spectral resolutions of 0.1nm and 0.07nm. Accurate AlO databases show a volley of applications in laboratory and astrophysical plasma diagnosis.