Our understanding of Alzheimer’s disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses, respectively. More recently, the p53 protein, well-known as ‘the guardian of the genome,’ has gained attention for its role in the early evolution of AD. This is due to p53’s central role in the control of oxidative stress and potential involvement in both Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can influence several processes in AD. The following review will explore the impact of p53 post-translational modifications (PTMs) on its function and consequential involvement in AD pathogenesis.

Soccer is the most played sport worldwide, with over 265 million participants. It is an incredibly demanding sport, with many different technical skills and physical loads placed on the body. This makes post-match recovery strategies amongst high level soccer players of great importance. The aim of this review is to summarize the existing literature on stretching for post-match recovery, examining its relation to injury prevention, Delayed Onset Muscle Soreness (DOMS), and performance. Scientific evidence of the highest quality and relevance was extracted and reviewed. Despite its common practice, evidence does not support static stretching as a modality to improve recovery post-match amongst soccer players. Larger trials with important outcome measures are needed to determine if a post-match stretching regimen to facilitate recovery exists.

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.

Impervious surface mapping with high-resolution remote sensing imagery has attracted increasing interest as it can provide detailed information for urban structure and distribution. Previous studies have suggested that the combination of LiDAR data and high-resolution imagery for impervious surface mapping performs better than using only high-resolution imagery. However, due to the high cost of the acquisition of LiDAR data, it is difficult to obtain the multi-sensor remote sensing data acquired at the same acquisition time for impervious surface mapping. Consequently, real landscape changes between multi-sensor remote sensing data at different acquisition times would lead to the error of misclassification in impervious surface mapping. This issue has mostly been neglected in previous works. Furthermore, the observation differences generated from multi-sensor data, including the problems of misregistration, missing data in LiDAR data, and shadow in high-resolution images would also challenge the final mapping result in the fusion of LiDAR data and high-resolution images. In order to conquer these problems, we propose an improved impervious surface mapping method incorporating both LiDAR data and high-resolution imagery at different acquisition times in consideration of real landscape changes and observation differences. In the proposed method, a multi-sensor change detection by supervised multivariate alteration detection is employed to obtain changed areas and misregistration areas. The no-data areas in the LiDAR data and the shadow areas in the high-resolution imagery are extracted by independent classification yielded by its corresponding single sensor data. Finally, an object-based post-classification fusion is proposed to take advantage of independent classification results with single-sensor data and the joint classification result with stacked multi-sensor data. Experiments covering the study site in Buffalo, NY, USA demonstrate that our method can accurately detect landscape changes and obviously improve the performance of impervious surface mapping.

The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large majority of the population. Structural equation modelling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. The survey was administered to 316 respondents across the United States by a survey corporation. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy, and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short and long-term side effects before a vaccine is released.

The potential of the Additive Manufacturing technologies is impeded by the surface finish obtained on the as-manufactured material. Therefore, the influence of various surface treatments, commonly applied to space hardware, on the mechanical properties of three selected metallic alloys (SS316L, AlSi10Mg, Ti6Al4V) prepared by using Selective Laser Melting (SLM) and Electron Beam Melting (EBM) additive manufacturing processes have been investigated. Within this study, SLM using EOS M400 and EOS M280 equipment and in addition EBM using an ARCAM Q20 machine have been applied for sample manufacturing. A half-automated shot-peening process followed by a chemical and/or electrochemical polishing or Hirtisation® process has been applied in order to obtain lower surface roughness compared to their as-received states. Special emphasize has been taken on their tensile, fatigue, and fracture toughness properties. In addition, their stress corrosion cracking (SCC) behaviour including microstructural analysis using HR-SEM have been investigated.

Recent wastewater testing suggests the poliovirus is reemerging, raising questions about the efficacy of the current inactivated polio vaccine and mass vaccination to eradicate poliomyelitis. The present study reassessed reported outcomes from the placebo-control study of the 1954 Salk inactivated poliomyelitis vaccine field trial, which studied a population of 1,829,916 U.S. school children from the first three grades. The placebo-control study of the trial reported that the polio vaccine was 80% to 90% effective in reducing cases of laboratory confirmed paralytic poliomyelitis, 60% to 70% effective against type 1 of the virus, and greater than 90% effective against types 2 and 3 of the poliovirus. However, these outcomes are reported as relative risk reductions, and the absolute risk reductions of the 1954 polio vaccine field trial were never reported to the public. The present paper’s analysis reveals to the public for the first time that the inactivated poliomyelitis vaccine's absolute risk reduction of laboratory confirmed paralytic poliomyelitis in the placebo-control study is 0.01% to 0.02%, an extraordinarily low clinical effect that impugns the Salk polio vaccine’s reported effectiveness. Furthermore, absolute risk reductions for the three poliovirus types are 0.01%, 0.00%, and 0.01%, respectively. Outcome reporting bias in the 1954 inactivated poliomyelitis vaccine field trial casts doubt on eradication of the poliovirus through mass vaccination.

Background—In 2011, Miller and Goldman published a study in Human and Experimental Toxicology that found a counterintuitive, positive correlation, r = 0.70 (r² = 0.49, p < .0001), demonstrating that as nations require more vaccine doses for their infants, infant mortality rates (IMRs) tend to increase (worsen). The dataset (n = 30) included the United States, a nation that required the most vaccines for their infants, and all nations with better IMRs than the United States. Dr. E. Bailey, a professor at BYU, and her students, recently read the Miller-Goldman study and found it "troublesome that this manuscript is in the top 5% of all research outputs" and falsely claimed that its findings were due to "inappropriate data exclusion," i.e., failure to analyze the "full dataset" of all 185 nations. The "Bailey reanalysis," titled Infant vaccination does not predict increased infant mortality rate: correcting past misinformation, was posted to the medRxiv preprint server on September 10, 2021 (version 1) and October 5, 2021 (version 3) and Europe PMC preprint server on September 10, 2021. Objective—This present study examines the various claims postulated by the Bailey reanalysis and assesses the robustness of their methodology, analyses, and reported results and conclusions. Methods—Data discussed in this paper are based on the previously mentioned study by Miller and Goldman and the Bailey reanalysis. Results—Linear regression analysis of IMR and the number of vaccine doses for each country yield a statistically significant positive correlation of r = 0.70 (p < .0001) for the top nations (n = 30) chosen by Miller-Goldman and r = 0.16 (p < .04) for the "entire dataset" chosen by Bailey et al (n = 185). Bailey also conducted linear regression analyses (for the year 2019) of IMRs as a function of vaccination rates for each of eight different vaccines and reported statistically significant inverse correlations for 7 of 8 vaccines over the entire range of vaccination rates. However, Miller and Goldman reanalyzed the Bailey analyses for nations with vaccination rates below 60% and found no statistically significant correlation for six vaccines (DPT, Hib, hepatitis B, polio, rotavirus, and measles) and statistically significant positive correlations for tuberculosis (r = 0.8, p < .005) and pneumococcal (r = 0.6 p < .023) vaccines. Conclusions—Bailey’s reanalysis corroborates a statistically significant positive correlation originally reported by Miller and Goldman. However, Bailey’s reported correlation (r = +0.16, p < .04) is small, likely due to poor methodology (failing to account for covariates, i.e., disparities among numerous socioeconomic factors that add uncertainty to their conclusion). The r-value reported by the Bailey reanalysis demonstrates an effect size that is about one-fourth (0.16/0.70) that reported by Miller-Goldman—underscoring how critically important it is for Bailey's reanalysis to eliminate confounding variables. Moreover, Bailey’s linear regression analyses of IMR as a function of vaccination rates for each of eight different vaccines demonstrate that some countries with low vaccination rates have low IMRs, while other countries with high vaccination rates have high IMRs. Rather than supporting a strong inverse correlation, the Bailey reanalysis demonstrates high vaccination rates are neither necessary nor sufficient to cause low IMR.

Background: Health Care Workers (HCWs) are at increased risk of acquiring and transmitting COVID-19 infection. Also, they present role models for communities with regards to attitudes towards COVID-19 vaccination. Hence, hesitancy of HCWs towards vaccination can crucially affect the efforts aiming to contain the pandemic. Previously published studies paid little attention to HCWs in Arab countries, which has a population of over 440 million. Objectives: to assess the rates of COVID-19 vaccine hesitancy in Arabic-speaking HCWs residing in and outside the Arab countries, and their perceived barriers towards vaccination. Methods: a cross-sectional study based on an online survey was conducted from 14-Jan 2021 to 29-Jan 2021, targeting Arabic-speaking HCWs from all around the world. Results: the survey recruited 5,708 eligible participants (55.6% males, 44.4% females, age 30.6±10 years) from 21 Arab countries (87.5%) and 54 other countries (12.5%). Our analysis shows a significant rate of vaccine hesitancy among Arabic-speaking HCWs residing in and outside Arab countries (25.8% and 32.8%, respectively). The highest rates of hesitancy were among participants from the west region of the Arab world (Egypt, Morocco, Tunisia, and Algeria). The most cited reasons for hesitancy were concerns about side effects and distrust in vaccine expedited production and healthcare policies. Factors associated with higher hesitancy included age of 30-59, previous or current suspected or confirmed COVID-19, female gender, not knowing the vaccine type authorized in the participant’s country, and not regularly receiving the influenza vaccine. Conclusion: this is the first large-scale, multinational, post-vaccine-availability study on COVID-19 vaccine hesitancy among HCWs. It reveals high rates of hesitancy among Arab-speaking HCWs. Unless addressed properly, this hesitancy can impede the efforts for achieving widespread vaccination and collective immunity.

Social media HPV vaccination interventions show promise for increasing HPV vaccination rates. An important consideration for the implementation of effective interventions into real-world practice in the translation potential, or external validity, of the intervention. To this end, we conducted a systematic literature review to describe the current body of evidence regarding the external validity of social media HPV vaccination-related interventions. Constructs related to external validity were based on the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. Seventeen articles published between 2006 and 2020 met inclusion criteria. Three researchers independently coded each article using a validated RE-AIM (reach, effectiveness/efficacy, adoption, implementation, maintenance) framework. Discrepant codes were discussed with a fourth reviewer to gain consensus. Of these 17 studies, three were pilot efficacy studies, 10 were RCTs to evaluate effectiveness, one was a population-based study, and three did not explicitly state which type of study was conducted. Reflecting this distribution of study types, across all studies the mean level of reporting RE-AIM dimensions varied with reach recording 90.8%, effectiveness (72.1%), adoption (40.3%), implementation (45.6%), and maintenance (26.5%). This review suggests that while the current HPV vaccination social media-driven interventions provide sufficient information on internal validity (reach and effectiveness), few have aimed to gather data on external validity needed to translate the interventions into real world implementation. Our data suggest that implementation research is needed to move HPV vaccination-related interventions into practice. Included in this review are recommendations for enhancing the design and reporting of these HPV vaccination social media-related interventions.

Clean production of renewable fuels is a great challenge of our scientific community. Iridium complexes have demonstrated a superior catalytic activity in the water oxidation (WO) reaction, which is a crucial step in water splitting process. Herein we have used a defective zirconium MOF with UiO-66 structure as support of a highly active Ir complex based on EDTA with formula [Ir(HEDTA)Cl]Na. The defects are induced by the partial substitution of tereftalic acid with smaller formiate groups. Anchoring of the complex occurs through a post-synthetic exchange of formiate anions, coordinated at the zirconium clusters of the MOF, with the free carboxylate group of the [Ir(HEDTA)Cl]-complex. The modified material was tested as heterogenous catalyst for the WO reaction by using Cerium Ammonium Nitrate as sacrificial agent. Although TOF and TON values are comparable to those of other iridium heterogenized catalysts, the MOF exhibits iridium leaching not limited at the first catalytic run, as usually observed, suggesting a lack of stability of the hybrid system under strong oxidative conditions.

Calibrating ecological models or making decisions with them is an optimisation problem with challenging methodological issues. Depending on the optimisation formulation, there may be a large variety of optimisation configurations (e.g. multiple objectives, constraints, stochastic criteria) and finding a single acceptable solution may be difficult. The challenges are exacerbated by the high computational cost and the non linear or elusive mathematical properties that increased with the complexity of numerical models. From the feedbacks of practitioners, the need for a guideline for conducting optimisation of complex models has emerged. In this context, we propose a practical guide for the complex model optimisation process, covering both calibration and decision-making. The guide sets out the workflow with recommendations for each step based on existing tools and methods usually scattered throughout the literature. This guide is accompanied with an ODDO template (Overview, Design, Details of Optimisation) to standardise the published description of model-based optimisation and suggests research directions.

Climacteric fruits are characterized by a dramatic increase in autocatalytic ethylene production, which is accompanied by a spike in respiration, at the onset of ripening. The change in the mode of ethylene production from autoinhibitory to auto-stimulatory is known as the system 1 (S1) to system 2 (S2) transition. Existing physiological models explain the basic and overarching genetic, hormonal, and transcriptional regulatory mechanisms governing the S1 to S2 transition of climacteric fruit. However, the links between ethylene and respiration, the two main factors that characterize the respiratory climacteric, have been largely understudied at the molecular level. Results of recent studies indicate that the AOX respiratory pathway may play an important role in mediating cross talk between ethylene response, carbon metabolism, ATP production, and ROS signaling during climacteric ripening. New genomic, metabolic, and epigenetic information sheds light on the interconnectedness of ripening-associated metabolic pathways, necessitating expanding the current, ethylene-centric physiological models. Understanding points at which ripening responses can be manipulated may reveal key, speciesand cultivar-specific targets for regulation of ripening enabling superior strategies for reducing postharvest wastage.

Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which causes considerable economic losses to the poultry industry worldwide. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing S1 and N proteins, mono-expressing S1 or N proteins alone of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, boosting with the same dose 14 days later, and following challenge with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels as well as the percentages of CD4+ and CD8+ T lymphocytes were detected within 28 days post-vaccination (dpv). The morbidity, mortality, and re-isolation of virus from the tracheas and kidneys of challenged birds were evaluated at 5 days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocyte in rHBM-S1-N group were higher than those of rHBM-S1 and rHBM-N groups, especially the cellular immunity response. At 5 dpc, the mortality, morbidity and virus re-isolation rate of rHBM-S1-N were slightly higher than those of H120 group, but were lower than those of rHBM-S1 group and rHBM-N group. The present study demonstrated that the protection of recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing S1 or N protein alone. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown cause characterized by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and more recently post-COVID-19 condition (Long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. Accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and Long COVID. To address this issue, this article aimed to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

This review critically assesses the body of research about Measles-Mumps-and-Rubella (MMR) vaccine attitudes and uptake in the United Kingdom (UK) over the past 10 years. We searched PubMed and Scopus, with terms aimed at capturing relevant literature on attitudes, uptake, decision-making, and beliefs about the MMR vaccine. Two researchers screened for abstract eligibility and after de-duplication 934 studies were selected. After screening, 40 references were included for full-text review and thematic synthesis by three researchers. We were interested in the methodologies employed, and grouped findings by whether studies concerned: (1) Uptake and Demographics; (2) Beliefs and Attitudes; (3) Healthcare Worker Focus; (4) Experimental and Psychometric Intervention; (5) Mixed Methods. We identified group and individual level determinants for attitudes, operating directly and indirectly, that influence vaccine uptake. We found that access issues, often ignored within the public “anti-vax” debate, remain highly pertinent. Finally, a consistent theme was the effect of misinformation and lack of knowledge or trust in healthcare, often stemming from the Wakefield controversy. Future COVID-19 immunisation campaigns for children should consider both access and attitudinal aspects of vaccination, and incorporate a range of methodologies to assess progress, taking into account socio-economic variables and the needs of disadvantaged groups.

The global COVID-19 pandemic claiming global spread continues to evolve, now to the verge of a third wave of outbreak possibly caused by the novel variants of concern of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The test positivity rate (TPR) and case fatal-ity rate (CFR) have increased steeply in the second wave of COVID-19 compared to the first. From the example of Kerala, a state in southern India, positivity increased from 1.33% at the peak of wave one in 10th June 2020 to 13.45% during 10th June 2021 in the second wave of pandemic. SARS-CoV-2 is an enveloped single-stranded RNA virus. Angiotensin-Converting Enzyme-2 (ACE-2) is a trans membrane surface protein present on multiple types of cells in the human body to which the viral spike protein attaches. Genetic variations in the SARS-CoV-2 and ACE2 receptor can affect the transmission, clinical manifestations, mortality and the efficacy of drugs and vaccines for COVID-19. Mutations are the primary cause of genetic variations. Given the high TPR and CFR, it is necessary to understand the variations of SARS-CoV-2 and cellular receptors of SARS-CoV-2 at the molecular level. In this review, we summarize the impact of genetic and ep-igenetic variations in determining COVID-19 pathogenesis and disease outcome.

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability and function. Here, we summarize these key regulatory events, with emphasis on how these affect their multi-functionality in health and disease.

Infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of the Spike S1 protein encoding mRNA, incorporated in a lipid nanoparticle, stabilized by polyethylene glycol (PEG). mRNA vaccines are novel in many respects, including cellular uptake, the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences encoding the SARS-CoV-2 Spike S1 protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to induction of virus neutralizing antibodies and cytotoxic T-lymphocytes will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. mRNA based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG, and potential presentation in the context of CD1 will be discussed. Adenovirus vector based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

COVID-19 pandemic that started in China has spread within 3 months to the entire globe. We tested the hypothesis that the vaccination against tuberculosis by BCG correlates with a better outcome for COVID-19 patients. Our analysis covers 55 countries complying with predetermined thresholds on the population size and number of deaths per million (DPM). We found a strong negative correlation between the years of BCG administration and the DPM along with the progress of the pandemic, corroborated by permutation tests. The results from multivariable regression tests with 23 economic, demographic, health-related, and pandemic restriction quantitative properties, substantiate the dominant contribution of BCG years to the COVID-19 outcomes. The analysis of countries according to an age-group partition reveals that the strongest correlation is attributed to the coverage in BCG vaccination of the young population (0-24 years). Furthermore, a strong correlation and statistical significance are associated with the degree of BCG coverage for the most recent 15 years, but no association was observed in these years for other broadly used vaccination protocols for measles and rubella. We propose that BCG immunization coverage, especially among the most recently vaccinated contributes to attenuation of the spread and severity of the COVID-19 pandemic.

If the world’s countries seriously tackle the climate targets agreed in Paris, their citizens are likely to experience substantial changes in production, consumption and employment. We present a long-run post-Keynesian model for studying the potential implications of a major transition on macroeconomic stability and employment. It is a demand-led model in which firms have considerable but not absolute freedom to administer prices, while household consumption exhibits inertia. Firms continually seek input-saving technological improvements that, in the aggregate, tie technological progress to firms' cost structure. Together with firm pricing strategies and wage setting, the productivities of different inputs determine the functional income distribution. Saving and investment, and production and purchase of consumption goods, are undertaken by different economic actors, driven by income and capacity utilization, with the possibility that productive capacity exceeds, or falls short of, effective demand. The model produces business cycles and long waves driven by technological change. We present results for a “downshifting” scenario in which households voluntarily withdraw labor and discuss the implications of downshifting for stability, growth, and employment. We contrast the downshifting scenario with ones in which households reduce consumption without withdrawing from the labor pool.

For centuries, crop plants have represented the basis of the daily human diet. Among them, cereals and legumes, accumulating oils, proteins and carbohydrates in their seeds, distinctly dominate modern agronomic practice. Indeed, these plants play an essential role in the food industry and fuel production. Therefore, the seeds of crop plants are intensively studied by food chemists, biologists, biochemists, and nutritional physiologists. Accordingly, not only seed development and germination, but also age- and stress-related alterations in seed vigor, longevity, nutritional value and safety can be addressed by a broad panel of analytical, biochemical and physiological methods. Currently, functional genomics is one of the most powerful tools, giving direct access to characteristic metabolic changes, accompanying plant development, senescence and response to biotic or environmental stress. Among individual methodological platforms, proteomics represents one of the most effective ones, giving access to cellular metabolism at the level of proteins. Here we discuss the main methodological approaches employed by seed proteomics in the context of physiological changes related to seed development, ageing and response to environmental stress.

We present a formalism to assess the safety of the COVID19 vaccines and infer a causal relation between vaccine administration and adverse effects, in particular death. We use data on adverse effects from VAERS covering the time interval [01-10-2020, 31-12-2021] (downloaded on 1 Feb 2022). We measure a vaccine fatality rate of order 0.01 for all vaccine manufacturers and identify a strong heterogeneity in the vaccine toxicity across vaccine lots, spanning up to four orders of magnitude. We compute the correlation between vaccination dates and death dates, and produce an estimate of the time lag that maximises the correlation, finding that the onset of adverse effects happened statistically (i.e. 32-41 percentiles) within one day after the vaccine administration and that death happened statistically (i.e. 22-50 percentiles) within about two weeks after the vaccine administration. These results provide data-based insights that can guide public health measures and health insurance policies.

Endometriosis is an oestrogen-dependant reproductive disease, with genetic, vascular, neural, inflammatory and auto-immune characteristics. There are many theories about the etiology of endometriosis, however, all of these theories have limitations and do not explain all the locations that endometriosis is found or types of patients with endometriosis. The objective of this paper is to postulate the hypothesis that endometriosis is caused by Maternal Microchimerism, the presence of maternal cells in the fetus. A literature review was conducted, analysing the characteristics, current etiological theories of endometriosis, theory limitations and relationship of maternal microchimerism and endometriosis. At time of writing, there was no literature on maternal microchimerism and endometriosis. These results suggest that Maternal Microchimerism could be a cause of endometriosis. This could account for the genetic and auto-immune characteristics seen in people with endometriosis, inducing a micro-environment for vascular, neural and epigenetic changes. This could also account for account for endometriosis seen in non-menstruating patients, such as men, fetuses and post-menopausal women and endometriosis found in non-peritoneal locations. If the hypothesis of Maternal Microchimerism is correct, endometriosis could be considered a pregnancy-related disease that could affect all humans, changing the accepted demographics of patients and potentially new diagnostic techniques and treatment options for patients with endometriosis. Further studies are needed to test this hypothesis.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

In this study, we surveyed over 600 participants to determine: a) major causes to mental stress during the pandemic and its future impacts, and b) diversity in public perception and acceptance (specifically for children) of Covid-19 vaccination. Statistical results and intelligent clustering outcomes indicate significant relationships between sociodemographic diversity, mental stress causes, vaccination perception, and Covid-19 infections. For instance, statistical results indicate significant dependence between mental stress due to Covid-19 and gender (p = 1.7e-05). Over 25% of males indicated work related stress comparing 35% in females however, females indicated more stressed (17%) due to relationships comparing to males (12%). Around 30% of Asian/Arabic participants don’t feel vaccination being safe as compared to 8% of white-British and 22% of white-European indicating significant dependence (p = 1.8e-08) with ethnicity. More specifically, vaccination acceptance for children is significantly dependent to ethnicity (p = 3.7e-05) where only 47% participants show willingness towards children’s vaccination. Primary dataset in this study along with experimental outcomes identifying sociodemographic information diversity with respect to public perception and acceptance of vaccination to children and potential stress factors might be useful for public and policy makers to be better prepared for future epidemics as well as working globally to combat mental health issues and running more effective vaccination campaigns.

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

The emergence of the COVID-19 pandemic has propelled the use of alcohol-based hand sanitizers to the fore as a SARS-CoV-2 control measure. To be effective these products must comply with relevant quality parameters such as alcohol concentration, methanol limits and purity. The current study was designed to determine the quality of alcohol-based hand sanitizer products in the Nairobi metropolitan area. For this purpose, 74 commercially marketed samples were collected and subjected to analysis by gas chromatography. Only three samples (4.1%) complied with the regulatory specifications for alcohol content, methanol limits and pH. Five samples (6.8%) complied with the specification for alcohol content but did not meet methanol or pH limits. A total of 44 (59.5%) samples had methanol levels that exceeded threshold limits. Eleven samples (14.9%) were found with methanol substitution (i.e., methanol, instead of ethanol or isopropanol, was the main alcohol component). The results show that users of alcohol-based hand sanitizers are being exposed to substandard and falsified products which in addition to being non-efficacious pose harm due to unacceptable levels of toxic impurities. Regular, routine post-market surveillance is needed to prevent such products from reaching the market.

Understanding the role of risk regions identified by genome-wide association studies (GWAS) have made considerable progress lately referred to the post-GWAS era. Annotation of the genes to the GWAS and fine-mapped functional variants, and understanding their biological pathway/gene networks enrichments is expected to give rich dividend by elucidating the mechanisms underlying prostate cancer. To this aim, we compiled and analysed currently available post-GWAS data on genes identified through GWAS and validated through experimental studies in prostate cancer to investigate molecular biological pathways enriched for assigned functional genes. The results highlight some well-known cancer signalling pathways, antigen presentation process and enrichment in cell growth and development gene networks suggesting prostate cancer may result from the accumulation of the effects of functional variants through multiple gene sets and pathways. The upstream analysis identifies critical transcription factors, which supplements the results regarding the regulatory role of the post-GWAS genes. We also identified the common genes between post-GWAS and three well-annotated prostate cancer Oncomine data in patient samples in order to uncover possible main genes in prostate cancer development/progression. Post-GWAS generated knowledge of gene networks and pathways, if analysed further and targeted appropriately, will have an important impact on clinical management of the disease.

Pseudomonas aeruginosa is a critical healthcare challenge due to its ability to cause persistent infections and the acquisition of antibiotic resistance mechanisms. Lack of preventive vaccines and rampant drug resistance phenomenon has rendered patients vulnerable. As new antimicrobials are in the preclinical stages of development, mining for the unexploited drug targets is also crucial. Here, we designed a chimeric vaccine against P. aeruginosa using a subtractive proteomics approach and identified nine unique enzymes as novel drug targets in PAO1 proteome. A total of five unique proteins were selected as potential vaccine candidates based on essentiality, extracellular localization, virulence, antigenicity, pathway association, protein-protein interaction analysis, hydrophilicity, and low molecular weight. These include two outer membrane porins OprF (P13794) and OprD (P32722), a protein activator precursor pra (G3XDA9), a probable outer membrane protein precursor PA1288 (Q9I456), and a conserved hypothetical protein PA4874 (Q9HUT9). These proteins were further analyzed using a reverse vaccinology approach to identify immunogenic and antigenic T cell and B cell epitopes. The best scoring epitopes qualifying for all set criteria were then further subjected to the construction of a polypeptide multi-epitope vaccine construct with cholera toxin B (CtxB) subunit as an adjuvant. The identified drug targets qualifying the screening criteria were: UDP-2-acetamido-2-deoxy-d-glucuronic acid 3-dehydrogenase WbpB (G3XD23), aspartate semialdehyde dehydrogenase (Q51344), 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase (Q9HV71), 3-deoxy-D-manno-octulosonic-acid transferase (Q9HUH7), glycyl-tRNA synthetase alpha chain (Q9I7B7), riboflavin kinase/FAD synthase (Q9HVM3), aconitate hydratase 2 (Q9I2V5), probable glycosyltransferase WbpH (G3XD85) and UDP-3-O-[3-hydroxylauroyl] glucosamine N-acyltransferase (Q9HXY6). For druggability and pocketome analysis crystal and homology structures of these proteins were retrieved and developed. A sequence-based search was performed in different databases (ChEMBL, Drug Bank, PubChem and Pseudomonas database) for the availability of reported ligands and tested drugs for the screened targets. These predicted targets may provide a basis for the development of reliable antibacterial preventive and therapeutic options against P. aeruginosa.

Visceral Leishmaniasis is a neglected tropical disease affecting 12 million people annually. Even in the second decade of the 21st century, it has remained without an effective vaccine for human use. In the current study, we have designed three multiepitope vaccine candidates by the selection of multiple IFN-γ inducing MHC-I and MHC-II binder T-cell specific epitopes from 3 previously identified antigen genes of Leishmania donovani from our lab, by immune-informatic approach using IFNepiotpe, NET-MHC-1 and NET MHC-2 webservers. We have tested the protective potential of these three multiepitope proteins as vaccine in a hamster model of visceral leishmaniasis. The immunization data revealed that the vaccine candidates induced a very high level of Th-1 biased protective immune response in-vivo in a hamster model of experimental visceral Leishmaniasis, with one of the candidates inducing a sterile immunity. The vaccinated animals displayed highly activated monocyte macrophages with the capability of clearing intracellular parasites due to increased respiratory burst. Additionally, these proteins induced activation of polyfunctional T cells secreting INF-γ, TNF-α, and IL-2 in ex-vivo stimulation of human peripheral blood mononuclear cells, further supporting the protective nature of designed candidates.

The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.

Background: Little is known about potential confounding factors influencing the humoral response in individuals having received the BNT162b2 vaccine. Methods: Blood samples from 231 subjects were collected before and 14, 28 and 42 days following COVID-19 vaccination with BNT162b2. Anti-Spike Receptor-Binding-Domain protein (anti-Spike/RBD) immunoglobulin G (IgG) antibodies were measured at each time-point. Impact of age, sex, childbearing age status, hormonal therapy, blood group, body mass index and past-history of SARS-CoV-2 infection were assessed by multivariable analyses. Results and Conclusions: In naïve subjects, the level of anti-Spike/RBD antibodies gradually increased following administration of the first dose to reach the maximal response at day 28 and then plateauing at day 42. In vaccinated subjects with previous SARS-CoV-2 infection, the plateau was reached sooner (i.e. at day 14). In the naïve population, age had a significant negative impact on anti-Spike/RBD titers at day 14 and 28 while lower levels were observed for males at day 42, when corrected for other confounding factors. BMI as well as B and AB blood groups had a significant impact in various subgroups on the early response at day 14 but no longer after. No significant confounding factors were highlighted in the previously infected group.

Open pit mining is a common activity in the Yucatan peninsula for the extraction of limestone. This mining is known under the generic name of quarries, and regionally as sascaberas (sascab=white soil in Mayan language). These areas are characterized by the total removal of the natural vegetation cover and soil in order to have access to the calcareous material. The present study shows the composition and structure of the vegetation in five quarries after approximately ten years of abandonment, and the conserved vegetation near to each one of the quarries in southeastern Quintana Roo. Using a canonical correspondence analysis (CCA), the distribution of the species was determined in relation to the edaphic variables: soil depth, percentage of organic matter (OM), cationic exchange capacity (CEC), pH and texture. 26 families, 46 genera and 50 species were recorded in the quarries and 25 families, 45 genera and 47 species were recorded in the conserved areas. The dominant species in the quarries belong to the families Poaceae, Fabaceae, Rubiaceae and Anacardiaceae. The quarries with higher values of OM (1.63%), CEC (24.05 Cmol/kg), depth (11 cm) and sand percentage (31.33%) include the following species like Lysiloma latisiliquum, Metopium brownei and Bursera simaruba which are commonly found in secondary forests. On the other hand, quarries with lower values of OM (0.39%), CEC (16.58 Cmol/kg) and depth (5.02), and higher percentage of silt (42.44%) were dominated by herbaceous species belonging to the Poaceae family and by Borreria verticillata, which are typical in disturbed areas of southeastern Mexico. In all cases, the pH was slightly alkaline due to the content of calcium carbonate (CaCO3), characteristic of the soils of the region. The edaphic variables are significantly correlated with the development and distribution of vegetation, and with the structure of the communities.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.

Declaration of smallpox eradication by the WHO on 1980 led to discontinuation of the world-wide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV) and the recent synthetic achievements, increases the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign as no other protective measure has been approved to achieve eradication and ensure world-wide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure, confers effective protection. The long incubation period and the uncertainty of the exposure status in the surrounding population calls for the development and evaluation of safe and effective methods that would allow to extend the therapeutic window and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements and open questions.

(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting of the Receptor-Binding Domain (RBD) of the SARS-CoV-2 spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice and non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against the WT isolate of the virus, and, with partners in India and Indonesia it was later developed into two closely resembling human vaccines, Corbevax and Indovac. Here, we describe the development and characterization of a next-generation vaccine adapted to the recently emerging XBB variants of SARS-CoV-2. (2) Methods: We conducted preclinical studies in mice using a novel yeast-produced SARS-CoV-2 XBB.1.5 RBD subunit vaccine candidate formulated with alum and CpG. We examined the neutralization profile of sera obtained from mice vaccinated twice intramuscularly at a 21-day interval with the XBB.1.5-based RBD vaccine, against WT, Beta, Delta, BA.4, BQ.1.1, BA.2.75.2, XBB.1.16, XBB.1.5 and EG.5.1 SARS-CoV-2 pseudoviruses. (3) Results: The XBB.1.5 RBD/CpG/alum vaccine elicited a robust antibody response in mice. Furthermore, serum from vaccinated mice demonstrated potent neutralization against the XBB.1.5 pseudovirus as well as several other Omicron pseudoviruses. However, regardless of high antibody cross-reactivity by ELISA, the anti-XBB.1.5 RBD antigen serum showed low neutralizing titers against the WT and Delta virus variants. (4) Conclusions: Whereas we observed modest cross-neutralization against Omicron subvariants by sera from mice vaccinated with the WT RBD/CpG/Alum vaccine or with the BA.4/5-based vaccine, sera raised against the XBB.1.5 RBD showed robust cross-neutralization. These findings underscore the imminent opportunity for an updated vaccine formulation utilizing the XBB.1.5 RBD antigen.

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.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Gonorrhea is a major global public health problem with emergence of multiple drug-resistant strains with no effective vaccine. This retrospective cohort study aimed to estimate the effectiveness of the New Zealand meningococcal B vaccine against gonorrhea associated hospitalization. The cohort consisted of individuals born 1984-1999 residing in New Zealand, therefore eligible for meningococcal B vaccination during 2004-2008. Administrative datasets of demographics, customs, hospitalization, education, income tax and immunization, were linked using the national Integrated Data Infrastructure. The primary outcome was hospitalization with a primary diagnosis of gonorrhea. Cox’s proportional hazards models were applied with a Firth correction for rare outcomes to generate estimates of hazard ratios. Vaccine effectiveness estimates were calculated as 1-Hazard Ratio expressed as percent. There were 1,143,897 eligible cohort members, with 135 missing information on gender, 16,245 missing ethnicity and/or 197,502 missing deprivation hence 935,496 were included in the analysis. After adjustment for gender, ethnicity and deprivation, vaccine effectiveness (MeNZB™) against hospitalization caused by gonorrhea was estimated to be 24% (95% CI 1-42%). In conclusion, vaccination with MeNZB™ significantly reduced the rate of hospitalization from gonorrhea. This supports prior research indicating possible cross protection of this vaccine against gonorrhea acquisition and disease in the outpatient setting.

In Italy HPV vaccination was implemented for girls since 2007 but its coverage was lower than recommended level. Sicily is one of the Italian administrative regions with lower vaccination coverage, ranging in the birth cohorts 1996–1999 from 59% to 62%. Aim of the study was to investigate factors associated with refusal of anti-HPV vaccination among young adult women of Palermo, Italy. A cross-sectional study was conducted through the administration of a telephone questionnaire, consisting of 23 items on HPV infection and vaccination knowledge based on Health Belief Model framework. The eligible population were young women with at least a previous vaccination among all included in Sicilian Vaccination schedule, without starting or completing anti-HPV vaccination schedule. Overall, 141 young women were enrolled, of them 84.4% were unvaccinated and 15.6% had at least one dose of HPV vaccine. In multivariate analysis, factors associated with the failure to perform the HPV vaccination were degree as school level (OR = 10.2, p = 0.041), lower participation at school seminar on HPV (OR = 0.2, p = 0.047) and lower perception of anti-HPV vaccine benefits (OR = 0.4, p = 0.048). Public health educational program focusing and tailored on benefits perception of anti-HPV vaccine and HPV disease severity, especially if carried out at school, can improve HPV vaccination uptake.

As shown earlier, the algorithmic complexity, like Shannon information and Boltzmann entropy, tends to increase in accordance with the general law of complification. However, the algorithmic complexity of most material systems does not reach its maximum, i.e. chaotic state, due to the various laws of nature that create certain structures. The complexity of such structures is very different from the algorithmic complexity, and we intuitively feel that its maximal value should be somewhere between order and chaos. I propose a formula for calculation such structural complexity, which can be called - structuredness. The structuredness of any material system is determined by structures of three main types: stable, dissipative, and post-dissipative. The latter are defined as stable structures created by dissipative ones, directly or indirectly. Post-dissipative structures, as well as stable, can exist for an unlimited time, but at the micro level only, without energy influx. The appearance of such structures leads to the “ratchet” process, which determines the structuregenesis in non-living and, especially, in living systems. This process allows systems with post-dissipative structures to develop in the direction of maximum structuring due to the gradual accumulation of these structures, even when such structuring contradicts the general law of complification.

Sustainable agriculture is essential to provide food security for a growing world population without further sacrificing the integrity of the environment. To make progress towards agricultural sustainability we must consider ecological and socioeconomic processes within the agricultural socio-ecosystem and involve stakeholders in the research process. We propose an innovative experimental approach for examining how natural regulation of ecosystems may provide an alternative to increasing external inputs in agriculture while improving the socio-economic welfare of farmers. These “social-ecological experiments” go further to participatory action research by not only involving stakeholders in the research process but also by manipulating simultaneously socioeconomic and ecological processes under real field conditions to give a faster route to sustainability. Social-ecological experiments are undertaken in real field conditions, explicitly involving stakeholders, and help untangle the drivers of social-ecological dynamics under various land management and farming practices. Social-ecological experiments are distinct from adaptive management and scenario-planning approaches as they highlight the interactions between ecological and social processes, manipulate the social and ecological processes shaping the system and show causal links between patterns and processes. As an example, we describe a social-ecological experiment for reducing herbicide use. Social-ecological experiments offer great opportunities for increasing stakeholders’ acceptance of environmental policies implemented through adaptive management. These experiments may help to identify management practices that optimize multiple objectives, deliver a portfolio of ecosystem services and satisfy key stakeholders.

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b compared to IgG1. Furthermore, we found that immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicates that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double dose dapsone combination therapy (DDD CT) for a total of 7-8 weeks. At the completion of therapy, all three patients major Lyme symptoms remained in remission for a period of 25-30 months. In conclusion, Double dose dapsone therapy could represent a novel and effective anti-infective strategy in chronic Lyme disease/PTLDS, especially in those individuals who have failed regular dose dapsone combination therapy (DDS CT) or standard antibiotic protocols. A randomized, blinded, placebo-controlled trial is warranted to evaluate the efficacy of DDD CT in those individuals with chronic Lyme disease/PTLDS.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naïve mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, introduction of genes encoding immunomodulatory functions into a candidate LAIV that can serve as natural adjuvants to improve overall vaccine safety and efficacy.

The poultry industry is affected by many epidemics and Newcastle Disease (ND) is a constant threat, known as a devastating disease for poultry farmers around the world. According to the average death time of chicken embryos, virus strains can be classified as lentogenic, mesogenic, or velogenic. The current research will clarify the vulnerable host range as well as the epidemiology and geographic distribution of ND in Pakistan. The introduction of the virus into poultry can have serious economic consequences, including the loss of production of sick and dying poultry, the cost of control measures (such as population reduction and disinfection measures), and possible trade restrictions in the event of an outbreak. The virus is transmitted by direct contact with sick poultry or carriers. Infected birds can also spread the virus in their feces. It can also be spread through respiratory secretions, contaminated feed, equipment, water, or feces. We will also discuss vaccines that which vaccines are available for NDV in Pakistan and vaccines can fight against this disease or not? In this study, a qualitative risk analysis was carried out to assess Pakistan's vulnerability to the introduction of virulent NDV strains

We employ the solution concept of ex post Nash equilibrium to predict the interaction of a finite number of agents competing in a finite number of basic games simultaneously. The competition is called a multi-game. For each agent, a specific weight, considered as private information, is allocated to each basic game representing its investment in that game and the utility of each agent for any strategy profile is the weighted sum, i.e., convex combination, of its utilities in the basic games. Multi-games can model decision making in multi-environments in a variety of circumstances, including decision making in multi-markets and decision making when there are both material and social utilities for agents as, we propose, in the Prisoner's Dilemma and the Trust Game. Given a set of pure Nash equilibria, one for each basic game in a multi-game, we construct a pure Bayesian Nash equilibrium for the multi-game. We then focus on the class of so-called uniform multi-games in which each agent is constrained to play in all games the same strategy from an action set consisting of a best response per game. Uniform multi-games are equivalent to multi-dimensional Bayesian games where the type of each agent is a finite dimensional vector with non-negative components. A notion of pure type-regularity for uniform multi-games is developed and it is shown that a multi-game that is pure type-regular on the boundary of its type space has a pure ex post Nash equilibrium which is computed in constant time with respect to the number of the types and is independent of prior probability distributions. We then develop an algorithm, linear in the number of types of the agents, which tests if a multi-game is pure type-regular on the boundary of its type space in which case it returns a pure ex post Nash equilibrium for the multi-game.

The current urban environment is faced with the potential threat of frequent natural disasters, and the sustainable development of post-disaster community has become a global issue. As an intrinsic motivation influencing the social interaction and capital operation of community, social network is an important mechanism promoting such sustainable development. However, the difference in social network caused by different member structure, spatial arrangement and management mechanism of post-disaster communities in different reconstruction modes has influenced such sustainable development process. Therefore, reasonable selection of reconstruction mode is crucial. This paper applied analytic hierarchy process to comprehensively measure and compare the social network strength in post-disaster communities in the four reconstruction modes adopted by the government of China, i.e. unified planning and unified construction, unified planning and independent construction, in situ reconstruction and relocation resettlement, with communities after the 2008 Sichuan earthquake in Chengdu, China as study objects from the perspective of three social relations (the relations between residents and residents, residents and managers, and residents and servers). The results showed that strong connections are generally presented in the social network of post-disaster communities in unified planning modes, that the strength is significantly higher than that of those in non-unified planning modes, and that the strength of UPIC communities is the highest. Meanwhile, government intervention, residents’ free participation and market operation are positively correlated to government trust, community interaction and community service respectively. The positive impact of government intervention is the most significant, but it has a peak value. No government management and excessive government intervention will exert negative impacts. The coordination of government, society and market is the key contents of post-disaster community reconstruction. The reconstruction modes based on “government leadership, resident participation and market operation” may become a feasible path for such sustainable development.

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.

Sexually transmitted infections (STIs) such as Gonorrhea is associated with serious morbidity and mortality rates in the world considering the multiple virulence factors possessed. The disease is manifested as salpingitis, pelvic inflammatory disease (PID), and bacteremia and is controlled by macrophages, dendritic cells, neutrophils, T cells, epithelial cells and cytokines. Dihydroliponamide acetyltransferase, a component of the mitochondrial pyruvate complex can be used as immunogenic target. Recent changes in the strain allowed the bacteria to acquire resistance against antibiotics.Vaccination remains an alternative to prevention against the disease. This study predicts an effective epitope-based vaccine against dihydrolipoamide acetyltransferase of Neisseria Gonorrhea using immunoinformatics approaches. Sequences retrieved from NCBI were passed on several prediction tests to analyze for possible B-cell, T-cell MHC class I epitopes and class II. Two epitopes showed high binding affinity for B-cells, while thirteen epitopes showed high binding affinity for MHCI and forty-five for MHCII. A population coverage of 100% for combined MHC I and II dictates the huge number of individuals who will benefit from formulating the vaccine. We recommend invivo and invitro studies to prove our prediction results.

DNA vaccines are stable, safe, cost effective to produce and relatively quick and easy to manufacture. However, to date DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits and macaques, at 4 to 10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.

The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax®, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins. CD4 T cell reactivity was mostly directed to HA/NA proteins in influenza B strains, and NP/M1/M2/NS1/NEP proteins in the case of the Influenza A strains. CD8 responses to both influenza A and B viruses preferentially targeted the more conserved core viral proteins. Following vaccination, both CD4 and CD8 responses against the various influenza antigens were increased in day 15 to day 91 post vaccination period and maintained a Th1 polarized profile. Importantly, no vaccine interference was detected, with the increased responses balanced across all 4 included viral strains for both CD4 and CD8 T cells, and targeting HA and multiple additional viral antigens.

The long-term laboratory aspects of the effects of COVID-19 on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical-laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older hospitalised in the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. Inflammatory markers such as ferritin > 300 U/L were observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST > 25 U/L, and GGT ≥ 50 or 32 U/L were associated with ALT > 29 U/L. There was a correlation between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID, especially in those hospitalised in the acute phase. In addition, ALT > 29 U/L was associated with other markers of liver injury, such as LDH, GGT, and ferritin.

Background and Objectives: Due to huge demand and availability of Banana, innovative cost effective method is necessary to promote and smoothen the banana production among farmers commercially mitigating the demand. Method and Materials: In this study, we feed cow dung mixture along with Urea, TSP, MoP, water to the distal part of rachis after cutting down male bud as soon as the female flowers matured into fruits (T1). The effect of this method was then compared with two control groups; one with the same strategy except fertilizer applied on root following ring method (C1, Positive control) and another was male flower untouched without applying fertilizer on rachis or root (C2, Negative control). Results and Conclusion: T1 showed more than double increase in length than controls. In the same way, in case of shape (diameter), T1 (0.46 cm) showed twice as better growth in the C1 (0.22 cm) and C2 (0.18 cm). Trend analysis showed the test group T1 curve is much steeper than the control groups suggesting faster growth rate than the other two. Finally, the cost of fertilizers for T1 per plant was estimated 0.091 USD while for positive control C1 it was 2.9 USD. This study shows an approach to be effective and economic comparing to traditional method of fertilizer application, which can be adapted as a new method of banana production.

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

In the recent days, lipid nanoparticles have been successfully emerged as one of the most advanced technology for highly efficient in vivo delivery of exogenous mRNA, especially for delivery of COVID-19 vaccines. For the vaccines to be successful or protective, they require highly efficient mRNA delivery systems. However, developing effective, translatable vaccines with better safety against some of the SARS‐CoV‐2 variants is still a challenge. Lipid nanoparticles (LNPs) are composed of four different types of lipids including ionizable lipids, helper or neutral lipids, cholesterol and polyethylene glycol (PEG) attached lipids. In this review, we present recent advancements and insights in designing the advanced LNPs and their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as the ionizable lipids are most important drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy were discussed. Finally, expert opinion of LNPs for mRNA vaccines were discussed which might address the future challenges in the development of mRNA vaccines employing highly efficient LNPs using novel set of ionizable lipids.

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.

There is growing recognition in research and policy of a mental health crisis among Canada’s paramedics but despite this, epidemiological surveillance of the problem is in its infancy. Just weeks before the emergence of the COVID-19 pandemic, we surveyed paramedics from a single, large, urban paramedic service in Ontario, Canada to assess for symptom clusters consistent with Post-Traumatic Stress Disorder (PTSD), major depressive disorder, and generalized anxiety disorder and to identify potential risk factors for each. In total, we received 589 completed surveys (a 97% completion rate) and found that 11% screened positive for PTSD, 15% for depression, and 15% for anxiety, with 1 in 4 active-duty paramedics screening positive for any of the three as recently as February 2020. In adjusted analyses, the risk of a positive screen varied as a function of employment classification, gender, self-reported resilience, and previous experience as a member of the service’s peer support team. Our findings support the position that paramedics screen positive for mental disorders at high rates – a problem likely to have worsened since the onset of the COVID-19 pandemic. We echo the calls of researchers and policymakers for urgent action to support paramedic mental health in Canada.

The urgency to develop vaccines against Covid-19 is putting pressure on the long and expensive development timelines which are normally required for development of lifesaving vaccines. There is a unique opportunity to take advantage of new technologies, smart and flexible design of clinical trials, and evolving regulatory science to speed up vaccine development against Covid-19 and transform vaccine development altogether.

Manual visual inspections typically conducted after an earthquake are high-risk, subjective, and time-consuming. Delays from inspections often exacerbate the social and economic impact of the disaster on affected communities. Rapid and autonomous inspection using images acquired from unmanned aerial vehicles offer the potential to reduce such delays. Indeed, a vast amount of re-search has been conducted toward developing automated vision-based methods to assess the health of infrastructure at the component and structure level. Most proposed methods typically rely on images of the damaged structure, but seldom consider how the images were acquired. To achieve autonomous inspections, methods must be evaluated in a comprehensive end-to-end manner, incorporating both data acquisition and data processing. In this paper, we leverage recent advances in computer generated imagery (CGI) to construct a 3D synthetic environment for simulation of post-earthquake inspections that allows for comprehensive evaluation and valida-tion of autonomous inspection strategies. A critical issue is how to simulate and subsequently render the damage in the structure after an earthquake. To this end, a high-fidelity nonlinear finite element model is incorporated in the synthetic environment to provide a representation of earthquake-induced damage; this finite element model, combined with photo-realistic rendering of the damage, is termed herein a physics-based graphics models (PBGM). The 3D synthetic en-vironment with PBGMs provide a comprehensive end-to-end approach for development and validation of autonomous post-earthquake strategies using UAVs, including: (i) simulation of path planning of virtual UAVs and image capture under different environmental conditions; (ii) au-tomatic labeling of captured images, potentially providing an infinite amount of data for training deep neural networks; (iii) availability of the ground truth damage state from the results of the finite-element simulation; and (iv) direct comparison of different approaches to autonomous as-sessments. Moreover, the synthetic data generated has the potential to be used to augment field datasets. To demonstrate the efficacy of PBGMs, models of reinforced concrete moment-frame buildings with masonry infill walls are examined. The 3D synthetic environment employing PBGMs is shown to provide an effective testbed for development and validation of autonomous vision-based post-earthquake inspections that can serve as an important building block for ad-vancing autonomous data to decision frameworks.

Smoking during pregnancy remains one of the most significant risk factors for poor birth outcomes. The Loma Linda University Health Comprehensive Tobacco Treatment Program (CTTP) is the largest maternal tobacco cessation program in San Bernardino County – the largest county in the contiguous US. CTTP is an eight week, incentivized, behavioral intervention for tobacco cessation for pregnant smokers. As part of program evaluation, we used a retrospective cohort design to assess smoking abstinence and to identify predictors of relapse/smoking after enrollment. Among CTTP cohort enrollees (n=233) from 2012-2013 we found: 1) a 28.4% 8 week point prevalence abstinence (PPA), and at a median of 9 months of follow-up after the PPA, 81.6% continued to indicate tobacco cessation, and 2) a high rate of relapse or loss to follow-up (56%). Our modeling of relapse/smoking after enrollment indicated that this was higher in young mothers, non-Hispanic mothers (White, Black), first/third trimester mothers, and rural mothers. The evaluation identified efficacy of the behavioral model at 8 weeks, but that relapse/smoking was occurring in disparity populations. Formative research is needed to expand the programmatic outreach and enrollment of mothers wanting to quit smoking.

Role identity theory describes the purpose and meaning in life that comes, in part, from occupying social roles. While robustly linked to health and well-being, this may become, however, when an individual is unable to fulfil the perceived requirements of an especially salient role in the way that they believe they should. Amid high rates of mental illness among public safety personnel, we interviewed a purposely selected sample of 21 paramedics from a single service in Ontario, Canada to explore incongruence between an espoused and able-to-enact paramedic role identity. Situated in an interpretivist epistemology, and using successive rounds of thematic analysis, we developed a framework for role identity dissonance wherein chronic, identity-relevant disruptive events cause emotional and psychological distress. While some participants were able to recalibrate their sense of self and understanding of the role, for others, this dissonance was irreconcilable, contributing to disability and lost time from work. In addition to contributing a novel perspective on paramedic mental health and well-being, our work also offers a modest contribution to the theory in using the paramedic context as an example to consider identity disruption through chronic workplace stress.

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.

Background: COVID-19 booster uptake remained poor among healthcare workers (HCW) despite evidence of improved immunity against Delta and Omicron variants. While most studies used a questionnaire to assess hesitancy, this study aimed to identify factors affecting true booster hesitancy by examining actual vaccine uptake across time. Method: COVID-19 vaccination database records among HCW working at 7 Singaporean public primary care clinics between January to December 2021 were extracted, with gender, profession, place of practice, vaccination type and dates. Time to booster was calculated from the date of vaccination minus date of eligibility. Chi-square test was used to compare relationship between 1st dose and booster hesitancy, Kaplan-Meier method and Log-rank test were adopted to evaluate differences in cumulative booster uptake. Multivariate cox regression was used to investigate predictors for timely booster vaccination. Vaccination rate was charted across time and corroborated with media releases pertaining to legislative changes. Results: 877 of 891 (98.9%) primary care HCW were fully vaccinated, 73.8% of eligible HCW had taken the booster. HCW were less booster hesitant [median 16 (5-31.3) days] compared to the 1st dose [median 39 (13-119.3) days]. 1st dose hesitant HCW were more likely to be booster hesitant (OR=3.66, 95%CI 2.61-5.14). Adjusting for sex, workplace and time to 1st dose, ancillary (HR=1.53, 95%CI 1.03-2.28), medical (HR=1.8, 95%CI 1.18-2.74) and nursing (HR=1.8, 95%CI 1.18-2.37) received boosters earlier compared with administrative staff. No temporal relationship was observed between booster uptake, legislative changes and COVID-19 infection numbers. Conclusion: Vaccine hesitancy among HCW had improved from booster to 1st dose, with timely booster vaccination among medical and nursing staff. Tailored education, risk messaging and strategic legislation might help to reduce delayed booster vaccination.

Plastid gene expression involves many post-transcriptional maturation steps resulting in a complex transcriptome composed of multiple isoforms. Although short read RNA-seq has considerably improved our understanding of the molecular mechanisms controlling these processes, it is unable to sequence full-length transcripts. This information is however crucial when it comes to understand the interplay between the various steps of plastid gene expression. Here, the study of the Arabidopsis leaf plastid transcriptome using Nanopore sequencing showed that many splicing and editing events were not independent but co-occurring. For a given transcript, maturation events also appeared to be chronologically ordered with splicing happening after most sites are edited.

Despite the remarkable success of SARS CoV-2 vaccines, the rise of variants, some of which are more resistant to the effects of vaccination, highlights the potential need for additional COVID-19 vaccines. We used the Multiple Antigen Presenting System (MAPS) technology, in which proteins are presented on a polysaccharide polymer to induce antibody, Th1, Th17 and CD8+ T cell responses, to engineer a novel vaccine targeting SARS CoV-2. This vaccine contains a fragment of the spike (S) protein receptor-binding domain (RBD) sequence of the original D614G strain and was used to immunize nonhuman primates (NHP) for assessment of immunological responses and protection against SARS CoV-2 challenge. The SARS CoV-2 MAPS vaccine generated robust neutralizing antibodies as well as Th1, Th17 and cytotoxic CD8 T-cell responses in NHPs. Furthermore, MAPS-immunized NHPs had significantly lower viral loads in the nasopharynx and lung compared to control animals. Taken together, these findings support the use of the MAPS platform to make a SARS CoV-2 vaccine. The nature of the platform also could enable its use for the inclusion of different variants in a single vaccine.

The novel coronavirus disease (COVID-19) has created immense threats to public health on various levels around the globe. The unpredictable outbreak of this disease and the pandemic situation are causing severe depression, anxiety and other mental as physical health related problems among the human beings. To combat against this disease, vaccination is essential as it will boost the immune system of human beings while being in the contact with the infected people. The vaccination process is thus necessary to confront the outbreak of COVID-19. This deadly disease has put social, economic condition of the entire world into an enormous challenge. The worldwide vaccination progress should be tracked to identify how fast the entire economic as well as social life will be stabilized. The monitor ofthe vaccination progress, a machine learning based Regressor model is approached in this study. This tracking process has been applied on the data starting from 14^th December, 2020 to 24^th April, 2021. A couple of ensemble based machine learning Regressor models such as Random Forest, Extra Trees, Gradient Boosting, AdaBoost and Extreme Gradient Boosting are implemented and their predictive performance are compared. The comparative study reveals that the AdaBoostRegressor outperforms with minimized mean absolute error (MAE) of 9.968 and root mean squared error (RMSE) of 11.133.

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

Eastern (EEEV) and Venezuelan (VEEV) equine encephalitis viruses (EEVs) are related, (+)ssRNA arboviruses that can cause severe, sometimes fatal, encephalitis in humans. EEVs are highly infectious when aerosolized, raising concerns for potential use as biological weapons. No licensed medical countermeasures exist; given the severity/rarity of natural EEV infections, efficacy studies require animal models. Cynomolgus macaques exposed to EEV aerosols develop fever, encephalitis, and other clinical signs similar to humans. Fever is nonspecific for encephalitis in macaques. Electrocardiography (ECG) metrics may predict onset, severity, or outcome of EEV-attributable disease. Macaques were implanted with thermometry/ECG radiotransmitters and exposed to aerosolized EEV. Data was collected continuously, and repeated-measures ANOVA and frequency-spectrum analyses identified differences between courses of illness and between pre-exposure and post-exposure states. EEEV-infected macaques manifested widened QRS-intervals in severely ill subjects post-exposure. Moreover, QT-intervals and RR-intervals decreased during the febrile period. VEEV-infected macaques suffered decreased QT-intervals and RR-intervals with fever onset. Frequency-spectrum analyses revealed differences in the fundamental frequencies of multiple metrics in the post-exposure and febrile periods compared to baseline and confirmed circadian dysfunction. Heart rate variability (HRV) analyses revealed diminished variability post-exposure. These analyses support using ECG data alongside fever and clinical laboratory findings for evaluating medical countermeasure efficacy.

The effectiveness of forest resources depends on the comprehensiveness and rationality of their consumption and processing into finished products. This article discusses a problem of utilising solid fir wood greenery residues generated during the industrial production of essential oils. Bioconversion is considered to be the most promising utilization method. The objective of this research was to study the chemical composition of bioconversion products of fir wood greenery-based substrates. The РР-3.2 strain of Pleurotus pulmonarius (Fr.) Quél was used as a biodestructor. In the process of bioconversion, the contents of polysaccharides and lignin substances is reduced to 38 and 28 % respectively. Up to 20 % of protein accumulates in bioconversion products of fir wood greenery. The amount of nucleic acids is not more than 1.5 g per 1 kg, the contents of heavy metals, such as mercury, cadmium, arsenic, lead, do not exceed maximum permissible concentration standards. The substrate weight loss reaches 15 %. When fallen leaves and post-extraction poplar bud residues are added to the substrate, the substrate-destroying activity of fungi rises, as well as the protein content increases by 3 %. The digestibility of products as a result of bioconversion increases 1.6–2.8 times depending on the substrate composition. The obtained data enable to recommend post-fermented substrates based on fir wood greenery and balsam poplar biomass for use as a protein feed additive.

Facing unprecedented global declines in the extent and integrity of ecosystems, the 15^th UN Biodiversity Conference (COP-15) in Kunming, China, presents an opportunity for transformative change. However, a lack of consensus on two key issues – resource mobilization and Access and Benefit Sharing (ABS) associated with Digital Sequence Information (DSI) – risks stalling negotiations for an ambitious ‘Post-2020 Global Biodiversity Framework’ as the next 10-year strategic plan under the Convention on Biological Diversity. We highlight systemic misconceptions concerning the financing of biodiversity and the burden this places on the ABS system. In the context of DSI, we caution that conflating ABS with resource mobilization risks disrupting modern science policy built on open access, with potentially severe ramifications for scientific research and innovation. To resolve these tensions, we call for a recalibration of discussions on ABS in order to maximize the value delivered by biodiversity for all of society, including indigenous peoples and local communities.

mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, mucosal administration of mRNA based on lipid nanoparticle technology faces challenges in clinical translation. In contrast, adenovirus-based vaccines induce strong T-cell responses and have been approved for intranasal delivery. To leverage the inherent strengths of both the mRNA and adenovirus platforms, we developed a novel modular adenoviral mRNA delivery platform based on Tag/Catcher bioconjugation. Specifically, we engineered adenoviral vectors integrating Tag/Catcher proteins at specific locales on the Ad capsid proteins, allowing us to anchor mRNA to the surface of engineered Ad viruses. In proof-of-concept studies, the Ad-mRNA platform successfully mediated mRNA delivery and could be optimized via the highly flexible modular design of both the Ad-mRNA and protein bioconjugation systems.

In this study an adjusting post-processing approach is implemented for improving intra-hourly forecasts of solar power and ramp events of PV solar power systems at different locations in the United States. This study also serves as an out-of-sample test to evaluate the performance of the adjusting approach with different locations and timescales. Thus, various individual intra-hourly forecasts of solar power are combined and adjusted by applying the adjusting approach. Both point and probabilistic forecasts of solar power are included. After that, solar power ramp event forecasting by the adjusting approach is carried out.

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

The paper presents new data on mineralogical-geochemical peculiarities of the granites and pegmatites of the Baikal area (Olkhon Region) with implications for the age, generation conditions and geodynamic settings of magmatism. The early Paleozoic granitoids of the Olkhon region are syncollisional formations produced from the gneiss-schistose substratum of the Olkhon metamorphic sequences. Pegmatoid granites and pegmatites of the Region were generated within a wide age range (458-390 Ma) and include different mineralogical and geochemical types. Amongst the Early Paleozoic granitoids, pegmatoid rocks are products of the collisional magmatism evolution and are similar to granites in terms of the mineral composition and distribution patterns of rare and rare earth elements. On the Olkhon island (Baikal lake) the pegmatite of the Tashkiney vein belong to the Be-Nb-Ta mineralogical-geochemical type demonstrating high contents of W, Sn U, Th and very low concentrations of Li and volatile components (F, B). In the Pryolkhonye area, vein pegmatite Iliksin is with Li, Be, Nb, Ta mineralization (lepidolite, vorobyevite, samarskite et al). The studied pegmatite veins are similar both by the profound negative Ba, Sr, Eu, and Zr anomalies. The zircons from the Tashkiney vein (390±5.0 Ma) and of the Iliksin vein (430.1±2.2 Ma, U-Pb isotope LA ICP MS metod) indicate the formation of pegmatite at the late post-collisional stage of magmatism in the Olkhon Region. As regard to mineralogical and geochemical characteristics, vein pegmatites with amazonite (Ainsky and Ulan-Nur) belong to the Li-F type. The tantalum mineralization, represented by microlites and minerals of the columbite-tantalite group is associated with the Ainsky amazonite pegmatite. As opposed to the Early Paleozoic syncollisional granitoids and pegmatoid formations, the middle Paleozoic vein bodies of pegmatites (Tashkiney, Iliksin, Ainsky, Ulan-Nur) are regarded as rare-metal pegmatites. In terms of geochemical characteristics, they are similar to the rare-metal pegmatoid granites and pegmatites of the intra-plate setting widespread in Mongolia and Transbaikalia. The rare-metal mineralization in the Olkhon region may be genetically related to the evolution of Be-Nb-Ta and Li-F types of the post-collisional granites and pegmatites.

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.

ME/CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome) is a chronic, complex, heterogeneous disease that affects millions and lacks both diagnostics and treatments. Big data, or the collection of vast quantities of data that can be mined for information, has transformed the understanding of many complex illnesses like cancer (1,2) and multiple sclerosis (3,4), by dissecting heterogeneity, identifying subtypes, and enabling the development of personalized treatments. It is possible that big data can reveal the same for ME/CFS. Solve M.E. developed and launched the You + ME Registry to collect longitudinal health data from people with ME/CFS, people with Long COVID (LC) and control volunteers using rigorous protocols designed to harmonize with other groups collecting data from similar groups of people. The Registry is an invaluable resource because it integrates with a symptom tracking app, as well as a biorepository, to provide a robust and rich dataset that is available to qualified researchers. Accordingly, it facilitates collaboration that may ultimately uncover causes and help accelerate the development of therapies.

In the Valpolicella area (Verona - Italy) Vitis vinifera cv. Corvina is the main grape variety used to produce Amarone wine. Before starting the winemaking process, the Corvina grapes are stored in a withering (i.e., dehydrating) warehouse until about 30% of the berry weight is lost (WL). This practice is followed to have the chemical metabolites concentrate in the berry and enrich the Amarone wine in aroma and antioxidant compounds. In compliance with the guidelines and strict Amarone protocol set by the Consorzio of Amarone-Valpolicella, withering must be carried out by setting the grapes in a suitable environment, either under controlled relative air humidity (RH) conditions and wind speed (WS) – no temperature modification is to be applied – or, following the traditional methods, in open-air natural environmental conditions. In general, the two processes have different dehydration kinetics due to the different conditions in terms of temperature, RH, and WS, which affect the accumulation of sugars and organic acids and the biosynthesis of sec-ondary metabolites such as stilbenes and glycoside aroma precursors. For this study, the two grape-withering processes were carried out under controlled (C) and not-controlled (NC) condi-tions and the final compositions of the Corvina dried grapes were compared also to evaluate the effects on the organoleptic characteristics of Amarone wine. The findings highlighted differences between the two processes mainly in terms of the secondary metabolites of the dried grapes, which affect the organoleptic characteristics of Amarone wine.

At present, there are no hardware or biochemical systems allow to assess the severity of post-COVID syndrome in vivo. The hardware of the proposed biotechnical system is based on routine transthoracic electrical impedance rheography, which makes it possible to register the frequency characteristics of the patient's bioimpedance response to controlled stress stimulation, thereby simultaneously fixing the characteristics of his productive heart, the state of the hemomicrocirculatory bed, the efficiency of the gas transport function of his blood, and also reliably assess personal reactivity and adaptive potential. Subsequent mathematical approximation of the obtained biometric data by an original neural network makes it possible to rank the results obtained and automatically generate a program of medical rehabilitation for a particular patient, depending on the severity of his post-COVID syndrome. The study results proved two reliable physiological signs confirming the presence of latent post-COVID complications: a decrease in the base impedance value for light exercise and an increase in the length of the systolic arc of the rheocardiogram.

Despite the research conducted worldwide, there is no treatment specific for SARS-CoV-2 infection with efficacy proven by randomized controlled trials. A chance for a breakthrough is vaccinating the majority of the global population. The public opinion surveys on vaccine hesitancy prompted our team to investigate the Polish medical community's attitude towards the SARS-CoV-2 and influenza vaccinations. In-person and online surveys of Healthcare Workers (HCWs): doctors, nurses, medical students, and other allied health professionals (n=419) took place between 14.09.2020 and 5.11.2020. In our study, 68.7% of respondents would like to be vaccinated with the COVID-19 vaccine. The safety and efficacy of vaccination against COVID-19 would persuade 86.3% of hesitant and those who would refuse to be vaccinated. 3.1% of all respondents claimed that no argument would convince them to get vaccinated. 61.6% of respondents declared a willingness to receive an influenza vaccination, of which 83.3% were also inclined to receive the planned COVID-19 vaccination. Although a significant part of respondents - 62.5% (262/419) indicated, they trusted the influenza vaccine more than the COVID-19 vaccine in direct comparison, more respondents intended to get the COVID-19 vaccination than the influenza vaccine in the 2020/2021 season.

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

In this paper the development process of a deployable modular sandwich panelized system for rapid assembly building construction is presented, and its structural performance under some different action effects is investigated. This system, which includes an innovative sandwich panel and its integrated connections, can be used as structural walls and floors in quickly assembled post-disaster housing, as well as load bearing panels for pre-fabricated modular construction and semi-permanent buildings. Panels and connections are composed of a pneumatic fabric formwork, and two 3-D high-density polyethylene (HDPE) sheets as the skins, filled with high-density rigid Polyurethane (PU) foam as the core. HDPE sheets manufactured with a studded surface considerably enhance the stress distribution, buckling performance and delamination strength of the sandwich panel under various loading conditions. The load-carrying behaviour of the system in accordance with some ASTM standards is presented here. The results show the system satisfies the codes criteria regarding semi-permanent housing.

Land-cover classification that uses very-high-resolution (VHR) remote sensing images is a topic of considerable interest. Although many classification methods have been developed, there is still room for improvements in the accuracy and usability of classification systems. In this paper, a novel post-processing approach based on a dual-adaptive majority voting strategy (D-AMVS) is proposed for improving the performance of initial classification maps. D-AMVS defines a strategy for refining each label of a classified map that is obtained by different classification methods from the same original image and fusing the different refined classification maps to generate a final classification result. The proposed D-AMVS contains three main blocks. 1) An adaptive region is generated by extending gradually the region around a central pixel based on two predefined parameters (T1 and T2) in order to utilize the spatial feature of ground targets in a VHR image. 2) For each classified map, the label of the central pixel is refined according to the majority voting rule within the adaptive region. This is defined as adaptive majority voting (AMV). Each initial classified map is refined in this manner pixel by pixel. 3) Finally, the refined classified maps are used to generate a final classification map, and the label of the central pixel in the final classification map is determined by applying AMV again. Each entire classified map is scanned and refined pixel by pixel based on the proposed D-AMVS. The accuracies of the proposed D-AMVS approach are investigated through two remote sensing images with high spatial resolutions of 1.0 and 1.3 m, respectively. Compared with the classical majority voting method and a relatively new post-processing method called general post-classification framework, the proposed D-AMVS can achieve a land-cover classification map with less noise and higher classification accuracies.

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

Background: Many randomized controlled trials (RCTs) and systematic reviews (SRs) on acupuncture treatment for post-acute stroke dysphagia have been published. Due to conflicting results an overview of SRs to summarize and assess the quality of this evidence to determine whether acupuncture is effective for this disease was conducted. Methods: Seven databases were searched for SRs and/or Meta-analysis of RCTs and quasi-RCTs on acupuncture for post-acute stroke dysphagia. Two authors independently identified SRs and meta-analyses, collected data to assess the quality of included SRs and meta analyses according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the revised Assessment of Multiple Systematic Reviews (AMSTAR 2). Results: 31 SRs were identified. Quality of 22 SRs was critically low, 5 SRs were low, and 4 Cochrane SRs were moderate when evaluated by AMSTAR2. 17 SRs reported 85.2-96.3% items of PRISMA. Five SRs included explanatory RCTs, 16 SRs included pragmatic RCTs, and 10 SRs included both. Conclusion: Currently evidence on the effectiveness of acupuncture on post-acute stroke dysphagia is low quality. Type of study appeared to have no direct influence on the result, but the primary outcome measures showed a relationship with the quality of SRs. High quality trials with large sample sizes should be the focus of future research. PROSPERO REGISTRATION NUMBER: CRD42019134163

Background: This study investigated the prevalence of worsening problems using Post Stroke Checklist (PSC) at 3, 6, and 12 months post-stroke and their associations with health-related quality of life. Methods: In stroke patients admitted between June 2014 and December 2015, PSC and EuroQol-5Dthree level (EQ-5D-3L) were assessed at post-stroke 3 (n=181), 6 (n=175), and 12months (n=89). The prevalence of worsening problems and its association withEQ-5D-3L at post-stroke 3 and 6months were analyzed. Results: An average of 0.59 (range 0–12), 1.47 (range 0–12), and 1.00 (range 0–10) worsening problems per patient was identified at 3, 6, and 12months after stroke, respectively. The most frequently and continuously identified worsening problems were mood disturbances (reported by 8.8%, 16.0% and13.5% of patients at 3, 6, and 12 months post-stroke, respectively). Worsening mobility was significantly associated with worse EQ-5D index at post-stroke 3 months (β,-0.583; 95% CI, -1.045 to -0.120). The worsening of mobility and communication was significantly associated with worse EQ-5D index at post-stroke 6 months (mobility: β,-0.170; 95% CI, -0.305 to -0.034, communication: β,-0.164; 95% CI, -0.309 to -0.020). Conclusions: PSC may be useful for the detection of various subjective worsening problems during serial clinical follow-up after stroke. Appropriate rehabilitation and management strategy to solve the identified problems could improve the quality of life in stroke survivors.

Introduction: The top priority of active immunoprophylaxis of pertussis is immunisation of infants as they can develop severe multiple-organ complications or even die from this disease. Objectives: The aim of the work is the identification of factors negatively affecting vaccine immunity to pertussis in preschool children prior to the administration of the first booster. Patients and Methods: The research was conducted on 352 children from 4.5 to 5.9 years of age who were hospitalised in the University Children’s Hospital in Lublin (Poland) from 1 January 2012 to 31 December 2015. The children taking part in the study had been administered all the mandatory vaccines from their birth to the age of 2 or 2.5 years old according to the Polish Immunisation Program 2008-2009. The immunoenzymatic method ELISA was applied to assess vaccine immunity to tetanus, diphtheria, pertussis, Haemophilus influenzae type b (Hib), poliomyelitis (IPV), mumps, rubella and measles. The level of vaccine antibodies to hepatitis type B was determined chemilumiscently. Results: The protective antibody titer was not found in 41 (11.65%) children before the administration of the booster. To verify the collective impact of parameters analised on antibody titer to pertussis, the Generalized Linear Model (GLZ) was used. Gender, type of vaccine, asthma, Hib and mumps antibody titers have been shown to be predicators of vaccine immunity to pertussis. Conclusions: Immunomodulation considered on the example of titer of IgG antibody to pertussis can serve as a useful model of the assessment of development of acquired immunity after mandatory vaccinations.

As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to alleviate this burden. However, the human antibody response is intricate and often obscure, with factors like antigenic seniority or original antigenic sin "OAS", and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.

Applications in security and electronic surveillance require combination of excellent magnetic softness with good mechanical and anti-corrosive properties and low dimensionality. We overviewed the properties of soft magnetic glass-coated microwires and different post-processing making them quite attractive for electronic article surveillance and security applications. We studied the magnetostatic interaction between the microwires and routes to tune the non-linear hysteresis loops by using the arrays of different types of amorphous microwires. The presence of neighbouring microwire (either Fe or Co-based) significantly affects the hysteresis loop of the whole microwires array. In a microwires array containing magnetically bistable microwires we observed splitting of the initially rectangular hysteresis loop with a number of Barkhausen jumps correlated with the number of magnetically bistable microwires. Essentially, non-linear and irregular hysteresis loops have been observed in mixed arrays containing Fe and Co-rich microwires. The observed non-linearity in hysteresis loops allowed to increase the harmonics and tune their magnetic field dependencies. Non-linear hysteresis loops have been also observed upon devitrification of amorphous microwires. On the other hand, several routes allowing to tune the switching field by either post-processing or modifying the magnetoelastic anisotropy have been reviewed. Observed unique combination of magnetic properties together with thin dimensions and excellent mechanical and anti-corrosive properties provide excellent perspectives for the use of glass-coated microwires for security and electronic surveillance applications.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Dengue is one of the life-threatening common neglected tropical diseases of the world, yet to develop any therapeutic for its treatment and prevention. Although there is a licensed vaccine reported, but becomes less efficacious due to the presence of multiple serovars of the dengue virus (DENV). Thus, an efficacious dengue vaccine potent to work against all the serovars is very crucial and time-demanding. Here we used a comprehensive hierarchical reverse vaccinology approach to design an epitope-based vaccine, targeted against multiple serovars of the DENV. Conservancy and population coverage analysis of the promiscuous epitopes revealed the robust immune response against multiple serovars of the DENV and various ethnicities. Final vaccine constructs comprising of B and T-cell epitopes, Universal pan-HLA DR or PADRE (AKFVAAWTLKAAA) sequence, and an adjuvant (β-defensin) at N-terminal of the construct with suitable linkers. Physiochemical properties and secondary structure profiling of the vaccine protein secured its hydrophilic, thermostable, and other structural nature. Molecular docking analysis indicates the deep binding of the proposed vaccine in the binding groove of the human immune TLR4 receptor present on the dendritic cell. In addition, disulfide engineering was coped to extend its stability. Furthermore, molecular dynamics simulation of the modeled vaccine-TLR8 complex showed minimum deformability. Finally, in silico cloning approach of the vaccine construct within an expression vector (pET28a+) assure good expression. Proposed vaccine may give novel insights for treatment of dengue patients.

Marburg virus disease (MVD) is a hemorrhagic fever and cause death up to 88% of people and is the same as Ebola virus, It is transmitted through skin contact or mucous membrane in the eyes, nose or mouth with blood or body fluids like urine, saliva sweat, feces and by object contaminated with body fluids. Despite these facts, yet there is no approved vaccine have been developed for the eradication of Marburg virus infections. Therefore, this study described a multi epitope-based peptide vaccine against Marburg virus viral protein 35, using several immunoinformatics tools combined with molecular docking studies. Utilizing Vaxijen 2.0 server, the V35 protein revealed to be antigenic with a score of 0.4316. Prediction of the T-cell and B-cell epitopes was then conducted. RTFDAFLGV epitope was found to be the most promising one with binding affinity to the highest numbers of MHC I alleles, a positive score in the Class I immunogenicity study and non-allergen. These results were further confirmed by the good interaction of RTFDAFLGV to the groove of HLA-A*02:01 with binding energy of -8.1 kcal/mole. Finally, the vaccine was cloned in silico to ensure its validity and efficiency of expression. To ensure its safety and immunogenic profile, in-vitro and in-vivo bioassays are recommended to confirm these findings.

Several researchers have contemplated deep learning-based post-filters to increase the quality of statistical parametric speech synthesis, which perform a mapping of the synthetic speech to the natural speech, considering the different parameters separately and trying to reduce the gap between them. The Long Short-term Memory (LSTM) Neural Networks have been applied successfully in this purpose, but there are still many aspects to improve in the results and in the process itself. In this paper, we introduce a new pre-training approach for the LSTM, with the objective of enhancing the quality of the synthesized speech, particularly in the spectrum, in a more efficient manner. Our approach begins with an auto-associative training of one LSTM network, which is used as an initialization for the post-filters. We show the advantages of this initialization for the enhancing of the Mel-Frequency Cepstral parameters of synthetic speech. Results show that the initialization succeeds in achieving better results in enhancing the statistical parametric speech spectrum in most cases when compared to the common random initialization approach of the networks.

We aimed to assess awareness, knowledge, and attitudes of healthy pregnant women towards human papillomavirus (HPV), to estimate factors associated with a positive attitude towards HPV immunization and to assess the uptake of the vaccine among their children. A cross-sectional study was conducted at the University Clinic of Gynecology and Obstetrics, Belgrade, Serbia among pregnant women attending their regular gynecological check-ups at the 12th gestational week. Knowledge about HPV and HPV vaccine was assessed using a specifically designed 12-item and 5-item questionnaires. Out of total 265 included women, 79.3% had heard of HPV, and 37.5% knew that HPV vaccine exists. HPV vaccine knowledge score was associated with higher odds for a positive attitude towards vaccination of both female (OR = 4.10, 95% CI 1.50-11.29) and male (OR = 3.71, 95% CI 1.52-9.01) child. The number of children (OR = 1.32, 95% CI 1.04-1.67) and high vaccine knowledge score (OR = 1.64 95% CI 1.13-2.39) were independent predictors associated with willingness to vaccinate child against HPV. The gynecologist was the preferable point of reference for information seeking about the HPV vaccine. Despite relatively high HPV awareness and knowledge among pregnant women in Serbia, about one-third of them are HPV vaccine aware, and are willing to vaccinate their children against HPV.