We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, open-label, phase 2/3 trial of a single 30-μg dose of monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine. Healthy participants had previously received ≥3 doses of a US-authorized mRNA vaccine, with the most recent being a bivalent Omicron BA.4/BA.5-adapted vaccine administered ≥150 days before study vaccination. In this analysis, Omicron XBB.1.5, BA.2.86, and JN.1 serum neutralizing titers were assessed at baseline and 1 month after vaccination in a subset of ≥18-year-olds (N = 40) with evidence of previous SARS-CoV-2 infection. Immunogenicity was also evaluated in a demographically matched group of participants who received bivalent BA.4/BA.5-adapted BNT162b2 in another study (ClinicalTrials.gov Identifier: NCT05472038). The XBB.1.5-adapted BNT162b2 vaccine elicited higher XBB.1.5, BA.2.86, and JN.1 neutralizing titers than those elicited by bivalent BA.4/BA.5-adapted BNT162b2. Overall geometric mean fold rises in neutralizing titers from baseline to 1 month after vaccination were higher among participants who received XBB.1.5-adapted BNT162b2 than those who received bivalent BA.4/BA.5-adapted BNT162b2 for XBB.1.5 (7.6 vs 5.6), slightly higher for JN.1 (3.9 vs 3.5), and similar for BA.2.86 (4.8 vs 4.9). ClinicalTrials.gov Identifier: NCT05997290.

The importance of conflict analysis and safety considerations during work zone intervals at signalized intersections cannot be overstated, as these periods pose unique challenges and safety risks for both motorists and pedestrians. Work zones introduce temporary changes to traffic patterns, lane configurations, and signal timings, which can disrupt the flow of traffic and increase the likelihood of conflicts between vehicles and pedestrians. By conducting comprehensive conflict analysis, it is possible to identify potential conflict points, such as merging areas, pedestrian crossings, and lane transitions, and implement targeted safety measures to mitigate risks. Additionally, considering safety considerations during work zone intervals is paramount to safeguarding the well-being of road users and minimizing the occurrence of conflicts or collisions. Measures such as enhanced signage, temporary traffic control devices, and increased enforcement efforts can help promote compliance with traffic regulations and ensure the safe passage of vehicles and pedestrians through work zones. This study investigates the dynamics of traffic behavior and safety implications within work zones at signalized intersections, aiming to address key challenges and enhance intersection management strategies. Through comprehensive analysis, varying frequencies of Vehicle-to-Vehicle (V2V) conflicts were observed across different movement directions, with significant occurrences identified in specific phases of the traffic signal cycle. Specifically, 69 V2V conflicts in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8 were recorded. Furthermore, the examination of Vehicle-to-Pedestrian (V2P) conflicts underscored the importance of prioritizing pedestrian safety, with notable occurrences observed in phases associated with pedestrian crossing movements. Meanwhile, despite the closure of left-turn movements, instances of red light running persisted, with 69 red light running events in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8.To mitigate these safety concerns during work zone intervals, proactive measures are essential. Strategies include improving communication through clear signage and advanced warning systems, enhancing enforcement efforts with red light cameras and increased police presence, and investing in infrastructure improvements such as temporary pedestrian facilities. Integration of real-time data from sensors, particularly LiDAR technology, offers significant advantages in detecting conflicts and red light runners during work zone intervals. LiDAR's precise, real-time data on vehicle and pedestrian movements, combined with its 360-degree coverage and high spatial resolution, facilitates accurate detection and tracking of potential conflict scenarios, contributing to enhanced intersection safety and traffic management efficiency. This study endeavored to conduct a traffic safety analysis during work zone intervals at a signalized intersection in Baltimore City, known for its high rate of traffic crashes, utilizing LiDAR sensor technology.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) infects dromedary camels and zoonotically infects humans, causing a respiratory disease with severe pneumonia and death. With no approved antiviral or vaccine interventions for MERS, vaccines are being developed for camels to prevent virus transmission into humans. We have previously developed a chimpanzee adenoviral vector-based vaccine for MERS-CoV (ChAdOx1 MERS) and reported its strong humoral immunogenicity in dromedary camels. Here, we looked back at total RNA isolated from three immunised dromedaries pre and post-vaccination during the first day; and performed RNA sequencing and bioinformatic analysis in order to shed light on the molecular immune responses following a ChAdOx1 MERS vaccination. Our finding shows that a number of transcripts were differentially regulated as an effect of the vaccination, including genes that are involved in innate and adaptive immunity, such as type I and II interferon responses. The camel Bcl-3 and Bcl-6 transcripts were significantly upregulated, indicating a strong activation of Tfh cells, B cell, and NF-kB pathways. In conclusion, this study gives an overall view of the first changes in the immune transcriptome of dromedaries after vaccination; it supports the potency of ChAdOx1 MERS as a potential camel vaccine to block transmission and prevent new human cases and outbreaks.

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

Tuberculosis (TB) remains a global health threat, necessitating innovative strategies for control and prevention. This comprehensive review explores the Mycobacterium tuberculosis Lysine Exporter (LysE) gene, unveiling its multifaceted roles and potential uses in controlling and preventing tuberculosis (TB). As a pivotal player in eliminating excess L-lysine and L-arginine, LysE contributes to the survival and virulence of M. tuberculosis. This review synthesizes findings from different electronic databases and includes 13 studies focused on the LysE of M. tuberculosis. The research unveils that LysE can be a potential drug target, a diagnostic marker for TB, and a promising candidate for vaccine development. The absence of LysE in the widely used BCG vaccine underscores its uniqueness and positions it as a novel area for TB prevention. In conclusion, this review underscores the significance of LysE in TB pathogenesis and its potential as a drug target, diagnostic marker, and vaccine candidate. The multifaceted nature of LysE positions it at the forefront of innovative approaches to combat TB, calling for sustained research efforts to harness its full potential in the global fight against this infectious disease.

Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug resistant (MDR) K. pneumoniae are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) K. pneumoniae (n=676) isolated from patients hospitalized in 13 intensive care units (ICUs) in 6 European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility. Majority were colistin-susceptible (CS) (n=597, MIC 2 µg/ml). 288 CS isolates were randomly selected for population analysis profiling (PAP) to assess CHR prevalence. CHR was detected in 108/288 CS K. pneumoniae. No significant association was found between the occurrence of CHR and country, MIC-value, K-antigen type and O-antigen type. Overall, 92% (618/671) of the K. pneumoniae were MDR with high prevalence among CS (540/592) and CR (98.7%, 78/79) isolates. In contrast, proportion of carbapenemase-producing K. pneumoniae (CP-Kpn) was higher among CR (72.2%, 57/79) than CS isolates (29.1%, 173/594). Proportions of MDR and CP-Kpn were similar among CHR (MDR: 85%, 91/107; CP-Kpn: 29.9%, 32/107) and CS isolates (MDR: 91%, 539/592; CP-Kpn: 29.1%, 153/59). WGS analysis of PAP isolates showed diverse insertion elements in mgrB or even among technical replicates underscoring the stochasticity of the CHR phenotype. CHR isolates showed high ST diversity (Simpson’s diversity index, SDI: 0.97, in 52 of the 85 STs tested). CR (SDI: 0.85) isolates were highly associated with specific STs (ST101, ST147, ST258/ST512, P ≤ 0.003). The widespread nature of CHR among MDR K. pneumoniae in our study urge the development of rapid HR detection methods to inform on the need for combination regimens.

The study investigated the usage of open data in public organizations, focusing on the motives, preferences, and governance ideals that determine their quality. The study shed light on how open data platforms are created and improved, as well as their influence on government operations. The primary goal was to understand the motivations behind the usage of open data, evaluate gov-ernance ideals, and examine institutions' efforts to standardize data formats. Hierarchical regres-sion analysis divides variables into core reasons and different preferences, demonstrating a need for "diversification" in order to use open data effectively. Efficiency, accountability, community impact, knowledge, and high-quality service delivery are all emphasized in governance value analysis. The institution's dedication to standardizing open data formats is evidenced by legislative measures and the integration of many technologies. The findings illustrate the institution's dual strategy of em-ploying traditional techniques and new technologies for effective data management. The report suggests increasing data openness and standardization, investing in ongoing training, upgrading alerting and awareness systems, and adopting specific regulations for open data use. Monitoring and feedback techniques are critical for adjusting and refining open data services to satisfy de-velopment needs. This study adds to the scientific knowledge of open data use by highlighting important motives, preferences, and governance ideals. The offered guidelines provide practical insights for public organizations looking to improve their open data platforms by promoting openness, efficiency, and community participation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 600 million cases and over 6 million deaths worldwide. Vaccination has been the main strategy used to contain the spread of the virus, and to avoid hospitalizations and deaths. Currently, there are two mRNA-based and one adenovirus vectored vaccines approved and available for use in the U.S. population. The versatility, low cost and rapid-to-manufacture attributes of DNA vaccines are important advantages over other platforms. However, DNA vaccination must meet higher efficiency levels for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been successfully used in the veterinary field. Here we evaluated the safety, immunogenicity and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate for delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. The results demonstrated that the linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects, and was able to elicit neutralizing antibodies and T cell responses using a low dose of the linear DNA construct in prime-boost regimen, and significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model.

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2022, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease through capping of the 5' end of DNA and RNA genomes respectively, which is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, which is a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16). Moreover, it was discovered that certain polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), directly silences important interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Other viral NSPs share a role with NSP1 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases.

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.

Globalization, knowledge economy, information technology advancements, and the rise of learning societies contribute to the concept of a learning city. The study examines the economic indicators of Yazd city, Iran, in the context of learning city development. A descriptive-analytical approach with a survey method and cluster sampling was employed. Data analysis involved Kolmogorov-Smirnov normality test, single-sample T-test, simple linear regression, and Kendall's W test. The normality test confirmed data normality. The T-test indicated that experts perceived the current state of most variables in Yazd as undesirable. Regression analysis revealed a significant positive association between the economic index and independent variables. Kendall's W test prioritized areas based on economic indicators, with the top 7 and bottom 5 areas identified for focused interventions. The study emphasizes the need to prioritize areas within Yazd based on their economic indicators. This prioritization informs strategies for enhancing social and legal aspects of Yazd's transformation into a learning city. Further research should explore effective methods to cultivate a full-fledged learning environment in the city.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in <5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in >55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p <0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of a HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation for stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations along with attenuating mutations E580G and S660A in PB1 of B/Bris (B/Bris PB1att 4M). Serial passage of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine.

Lily tepals have a short lifespan. Once the tepals senesce, the ornamental value of the flower is lost. Some cultivars have attractive purple ovaries and fruits which greatly enhance the ornamental value of Asiatic hybrid lilies. However, little is known about the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries. To investigate the transcriptional network that governs purple ovary coloration in Asiatic hybrid lilies, we obtained transcriptome data from green ovaries (S1) and purple ovaries (S2) of Asiatic ‘Tiny Padhye’. Comparative transcriptome analysis revealed 4228 differentially expressed genes. Differential expression analysis revealed that nine unigenes including four CHS genes, one CHI gene, one F3H gene, one F3′H gene, one DFR gene, and one UFGT gene were significantly up-regulated in purple ovaries. One MYB gene, LhMYB12-Lat, was identified as a key transcription factor determining the distribution of anthocyanins in Asiatic hybrid lily ovaries. Further qPCR results showed unigenes related to anthocyanin biosynthesis were highly expressed in purple ovaries of Asiatic ‘Tiny Padhye’ at stages 2 and 3, while they showed an extremely low level of expression in ovaries of Asiatic ‘Yellow Pixels’ during all developmental stages. In addition, shading treatment significantly decreased pigment accumulation by suppressing the expression of several unigenes related to anthocyanin biosynthesis in ovaries of Asiatic ‘Tiny Padhye’. These results could further our understanding of the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries.

Aim: To investigate inflammation indices and erythropoietin (EPO) levels for their potential role in distinguishing polycythemia vera (PV) from secondary polycythemia (SP), and to compare different parameter combinations in terms of diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. PV diagnosis was made according to the 2016 WHO criteria (n=145). Those who did not fulfill the criteria were defined as having SP (n=84). Results: NLR, PLR and SII were significantly higher in the PV group (p

Avian necrotic enteritis is an enteric disease of broiler chickens caused by certain pathogenic strains of Clostridium perfringens in combination with predisposing factors. A vaccine offering complete protection against the disease has not yet been commercialized. In a previous study, we produced five recombinant proteins predicted to be surface-exposed and unique to necrotic enteritis-causing C. perfringens and the immunogenicity of these potential vaccine candidates was assessed in broiler chickens. In the current work, the relative contribution of the antibodies raised by these putative antigens to protect broiler chickens was evaluated using an experimental necrotic enteritis induction model. Additionally, the link between the immune response elicited and the gut microbiota profiles in immunized birds subjected to infection with virulent C. perfringens was studied. ELISA results showed that the IgY antibody titers in vaccinated birds on days 21 and 33 were significantly higher than those on days 7 and 14 and those in birds receiving the adjuvant alone, while the relative contribution of the specific immunity attributed to these antibodies could not be precisely determined using this experimental NE induction model. Besides, 16S rRNA gene amplicon sequencing showed that immunization of birds with recombinant proteins had a low impact on the chicken caecal microbiota.

African swine fever (ASF) is a pandemic threat to the global pig industry and wild suids. A safe and efficacious vaccine could monumentally assist in disease eradication. In the past years, promising live attenuated vaccine candidates emerged in proof-of-concept experiments, among them, “ASFV-G-∆MGF”. In our study, we tested the vaccine candidate in three animal experiments intramuscularly in domestic pigs one orally in wild boar. Further, a macrophage-grown vaccine virus and a virus grown on permanent cells could be employed. Irrespective of the production system of vaccine virus, a two-dose intramuscular immunization could induce close to sterile immunity with full clinical protection against challenge infection. After oral immunization, 50% of the vaccinees seroconverted and all responders were completely protected against subsequent challenge. All non-responders developed ASF upon challenge with two acute lethal infections and two mild and transient courses. The latter results show a lower efficiency after oral administration that would have to be taken into consideration when designing vaccination-based control measures. Our findings suggest that “ASFV-G-∆MGF” could help to contain the disease under an appropriate vaccination campaign. Further research is needed to characterize safety aspects and define possible improvements of oral efficiency.

The outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes severe respiratory infection (COVID-19) has spread in China, and the world health organization declared it pandemic. However, no approved drug or vaccines are available, and treatment is mainly supportive and through a few repurposed drugs. In this urgency situation, development of SARS-CoV-2 based vaccines is immediately required. Immunoinformatic and molecular modelling are generally used time-efficient methods to accelerate the discovery and design of the candidate peptides for vaccine development. In recent years, the use of multiepitope vaccines is proved to be a promising immunization strategy against viruses and pathogens, which induce more comprehensive protective immunity. The current study demonstrated a comprehensive in-silico strategy to design stable multiepitope vaccine construct (MVC) from B-cell and T-cell epitopes of essential SARS-CoV-2 proteins with the help of adjuvants and linkers. The integrated molecular dynamics simulations analysis revealed the stability of MVC and its interaction with human Toll-like receptors (TLRs), which trigger an innate and adaptive immune response. Later, the in-silico cloning in a known pET28a vector system also estimated the possibility of MVC expression in E. Coli. Despite this study lacks validation of this vaccine construct in terms of its efficacy, the current integrated strategy encompasses the initial multiple epitope vaccine design concepts. After validation, this MVC can present to be a better prophylactic solution against COVID-19.

COVID-19 vaccine hesitancy and its enablers would shape community uptake of non-covid vaccines such as oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included characteristics, intention to take OCV and COVID-19, reasons for COVID-19 hesitancy, and thinking and feeling about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude Prevalence Ratio, [cPR]=1.12, 95%CI[1.03-1.21]). Independent predictors of OCV hesitancy were living in semi-urban area (adjusted Prevalence Ratio [aPR]=1.10, 95%CI[1.03-1.12]), religious refusal of vaccines (aPR=1.06, 95%CI[1.02-1.12]), concerns about vaccine safety (aPR=1.05, 95%CI[1.01-1.11]) and adverse effects (aPR=1.06, 95%CI[1.01-1.12]), as well as poor knowledge (aPR=1.07, 95%CI[1.01-1.14]). Conversely, the belief about COVID-19 vaccine effectiveness reduced OCV hesitancy (aPR=0.76, 95%CI[0.62-0.93]). COVID-19 vaccine hesitancy and its drivers exhibiting a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy interventions would likely improve the introduction of novel non-COVID-19 vaccines in post-COVID-19 era.

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.

Stallion mules have been used as working equids in several countries. Aggressiveness, under the influence of testosterone, resulted in the necessity for surgical castration before work training. The gonadotropin-releasing hormone (GnRH) vaccine may be an alternative method for immunocastration in mules. The objectives were to evaluate the effect of GnRH vaccine on anti-GnRH antibody production, serum testosterone level, clinical adverse effects, and behavior toward human manipulation. Twenty-five mules were separated into 3 groups: Control-intact, Control-castrated, and Treatment. Treatment was further divided into subgroups according to condition (intact or unilateral cryptorchid) and age. Treatment received 195 µg GnRH vaccine intramuscularly at week 0, 4, and 8. Anti-GnRH antibody increased at week 6 and 10, then gradually decreased to baseline at week 22. Treatment-intact-young had the highest anti-GnRH antibody, resulting in lower serum testosterone levels during week 2-6 and 12-16 compared to Control-intact. Subcutaneous edema adjacent to the injection site was detected only in Treatment-intact after booster vaccination. During week 6-22, the behavioral scores of Treatment significantly changed toward at ease with human contact compared to a score before vaccination. In conclusion, mules responded to GnRH vaccine, which could temporarily suppress testosterone for up to 16 weeks.

Background: Respiratory syncytial virus[ RSV] is a lethal overwhelming defectiveness that influences people all over the world. The infection gets down in the lower respiratory tract and does not disperse to the remainder of the body. The objective of the study: Bioinformatics was used to create an mRNA vaccine against the Respiratory syncytial virus( RSV). Methodology: Lipid nanoparticle vaccines containing the Respiratory syncytial virus's surface fusion protein's mRNA were created for the current screening experimental investigation. Lipid nanoparticles[ LNP] with a particle size of around 90 nanometres that were created using the hot micro-emulsion process comprise the current vaccine delivery system. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current immunization lacks antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies worsen infection by enhancing viral entrance and replication in the host cells, activating cytokines and the complement cascade through the production of immunological complexes, or both. However, the current LPN-RSV mRNA vaccine of the surface fusion protein resulted in the formation of potent neutralizing antibodies with persistent protection, especially for newborns and elderly individuals who get the ideal dose regimen. Conclusion: The invention of the LNP-mRNA RSV vaccine, which might prevent RSV-caused bronchiolitis and fatal pneumonia, made the current study promising

Despite the importance of influenza vaccination for healthcare workers (HCWs), their uptake remains challenging. This study aimed to measure influenza vaccine hesitancy among HCWs in Nakhon Phanom province, Thailand. A representative cross-sectional survey was conducted at six hospitals during August – September 2020 using a self-administered questionnaire. HCWs delaying getting influenza vaccines, accepting but unsure, or refusing with doubts were categorized as hesitant. Those accepting without any doubts were classified as non-hesitant. Vaccine hesitancy determinants were identified by multivariable logistic regression analysis. A total of 338 participants (97%) completed the questionnaires; most were female nurses working at district hospitals without pre-existing chronic medical conditions. Nearly 60% of participants (197/338) exhibited influenza vaccine hesitancy, and significant factors included age above 50 years adjusted odds ratio [aOR] 3.2, 95% CI 1.3-8.5), fair knowledge of influenza/vaccination (aOR 0.4, 95% CI 0.2-0.8), and negative influence of other HCW (High level– aOR 2.3, 95% CI 1.1-4.8; Moderate level- aOR 2.1, 95% CI 1.1-4.4). Imparting updated information to the HCW combined with positive guidance from influential peers may help reduce this hesitancy.

Background: Annual influenza epidemics are a serious public health problem, causing particularly severe morbidity and mortality in high-risk groups. The study aimed to understand Poles' attitudes and beliefs towards influenza vaccinations in the flu season of 2022–2023, analyze preferences and unmet needs regarding influenza vaccinations, and examine the perception and acceptance of the influenza vaccine among individuals at risk of flu complications. Methods: A cross-sectional survey-based study was carried out on a sample of 1446 respondents. The Google Forms questionnaire was created and disseminated electronically using social media and e-mail. The pre-test was performed at the beginning of the project. Results: The majority of respondents (71%) could identify "high-risk groups" recommended for influenza vaccination. Furthermore, it was observed that individuals aged 21 to 59 demonstrated a higher level of knowledge in this regard compared to those below 20 and above 65 years old, and individuals with higher and medium education levels were much better at identifying risk groups for influenza virus infection. The majority of respondents (52.01%) reported receiving influenza vaccination at some point in the past, with 32.12% receiving it in the 2022–2023 flu season and 41.09% in the 2021–2022 season. The majority of respondents declaring acceptance of the vaccine for the 2022-2023 season were in the high-risk group. Only 17.28% of respondents declared receiving both influenza and SARS-CoV-2 vaccines in the 2022-2023 season, with the vast majority being respondents from the "high-risk group" (p

Chlamydia trachomatis (Ct) infections are the most common sexually-transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we use the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial protease-like activity factor (CPAF) protein. We tested two weekly administration options – twice intranasal (IN) followed by twice intramuscular (IM), or twice IM followed by twice IN. We assessed the humoral immune response not only in serum by CPAF-specific IgG including antibody avidity determination but also in cervical and rectal swabs by CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed upon in vitro CPAF-restimulation via IFN-γ and IL-17 ELISpots as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response: Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response by CD4 T cells. In the IM/IN vaccinated pigs, these cells also significantly downregulated their CCR7 expression – a sign for differentiation into peripheral tissue homing effector/ memory cells. Conclusively, this study demonstrates strong immunogenicity of the IM/IN administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected tropical disease of the Americas has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. The burden of disease in outside the U.S. remains poorly understood. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection, especially involving the meninges, is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine has not yet resulted in a clinically useful product, scientific efforts of vaccine development pave the way for future success.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

Vaccines decrease morbidity and mortality. Nevertheless, their benefits depend on public response. During COVID-19, vaccine hesitancy and refusal were rampant, threatening public health. A thorough understand-ing of opponents' arguments is required to address the diffusion of unreliable information on social media and prevent vaccine hesitancy from developing into vaccine refusal. Accordingly, the article examines vac-cine opponents' justifications on social media. Textual content analysis of reader comments on three health-related Israeli Facebook pages was conducted. Data collection encompassed the Israeli COVID-19 vaccination period from October 2020 to May 2022. The comments were analyzed according to the health beliefs model (HBM). We found that vaccine opponents were characterized by low perceptions of the severity of the disease combined with high perceptions of the damages of the vaccine; low perceived benefits of vac-cine compliance; vaccine hesitancy and fear along with public distrust as barriers to change; and call for ac-tion to resist the vaccine and spread related anti-establishment views on the web. As vaccination hesitancy was found to develop into public distrust in the state systems and escalate into conspiracy beliefs and an-ti-vaccination activism, its early detection may prevent future vaccine resistance.

Chikungunya virus (CHIKV), a single-stranded RNA virus transmitted by Aedes mosquitoes, poses a significant global health threat, with severe complications observed in vulnerable populations. The only licensed vaccine, IXCHIQ, approved by the USFDA, is insufficient to address the growing disease burden, particularly in endemic regions lacking herd immunity. Monoclonal antibodies (mAbs), explicitly targeting structural proteins E1/E2, demonstrate promise in passive transfer studies, with mouse and human-derived mAbs showing protective efficacy. The article explores various vaccine candidates, including live attenuated, killed, nucleic-acid-based (DNA/RNA), virus-like particle, chimeric, subunit, and adenovirus vectored vaccines. RNA vaccines emerge as promising candidates due to their rapid response capabilities and enhanced safety profile. The review underscores the importance of E1 and E2 proteins as immunogens, emphasising their antigenic potential. Several vaccine candidates, such as CHIKV/IRES, measles vector (MV-CHIK), synthetic DNA-encoded antibodies, and mRNA-lipid nanoparticle vaccines, demonstrate encouraging preclinical and clinical study results. In addition to identifying potential molecular targets for antiviral therapy, the study looks into the roles played by Toll-like receptors, RIG-I, and NOD-like receptors in the immune response to CHIKV. It also offers insights into novel tactics and promising vaccine candidates.

Abstract: Lipidic carriers employed for the entrapment, encapsulation and precise targeting the bioactive compounds offer significant advantages to the biomedical, pharmaceutical, nutraceutical and cosmeceutical industries. These lipid and phospholipid-based vesicles can improve the solubility, permeation, pharmacokinetics, pharmacodynamics and bioavailability of the encapsulated material. As a matter of fact, nano-sized phospholipid vesicles have attained the highest success rate in commercialization among the available drug encapsulation technologies. Nevertheless, developing industrially acceptable products still remains a challenge. Among the main disadvantages of conventional lipidic carriers are their instability in the biological environments, and their sensitivity to changes in the pH, temperature and enzymes. To overcome these problems, the new generation of phospho/lipid-based carrier systems was developed using ingredients from microorganisms living in extremely harsh environments (i.e., archeaeobacteria). The present entry aims to review unique features of archaeolipids and recent developments in their application for the encapsulation of genetic material as well as their role and function as adjuvants and vaccine candidates.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

Aleutian mink disease virus (AMDV) is known to cause the most significant disease in the mink industry. It is globally widespread and manifested as a deadly plasmacytosis and hyperglobulinemia. So far, measures to control viral spread have been limited to manual serological testing for AMDV-positive mink. Further, due to the persistent nature of this virus, attempts to eradicate Aleutian disease (AD) have largely failed. Therefore, effective strategies to control viral spread are of crucial importance for wildlife protection. One potentially key tool in the fight against this disease is by immunization of mink against AMDV. Throughout many years, several researchers have tried to develop AMDV vaccines and demonstrated varying degrees of protection in mink by those vaccines. Despite these attempts, there are currently no vaccines available against AMDV, allowing the continuation of the spread of Aleutian disease. Herein, we summarize previous AMDV immunization attempts in mink as well as other preventative measures with the purpose to shed light on future studies designing such a potentially crucial preventative tool against Aleutian disease.

Background: Identification of cancer biomarkers that are differentially expressed (DE) under two biological conditions is an important task in many microarray studies. There exist several methods in the literature in this regards and most of these methods designed especially for unpaired samples, which does not satisfy the requirements of paired samples where the gene expressions are taken from the same patients before and after treatment. Furthermore, the traditional biomarker identification methods based on either p-values or fold change (FC) values. However, sometimes, p-value based results do not comply with FC based results due to the smaller variance of gene expressions. There are some methods that combine both p-values and FC values to solve this problem. But, these methods also show weak performance for small-sample case in presence of outlying expressions. To overcome this problem, in this paper an attempt is made to develop a hybrid robust SAM-FC approach by combining rank of FC values and rank of p-values based on SAM statistic using minimum β-divergence method, which is designed for paired samples. This method introduces a weight function known as β-weight function. This weight function produces larger weights corresponding to usual/normal expressions and smaller weights for unusual/outlying expressions. The β-weight function plays the significant role on the performance of the proposed method. Results: The proposed method uses β-weight function as a measure of outlier detection by setting β=0.2. We unify both classical and robust estimates using β-weight function such that maximum likelihood estimators (MLEs) are used in absence of outliers and minimum β-divergence estimators are used in presence of outliers to obtain reasonable p-values and FC values in the proposed method. We examined the performance of proposed method in a comparison of some popular methods (t-test, SAM, LIMMA, Wilcoxon, WAD, RP and FCROS) using both simulated and real gene expression profiles for both small-and large-sample cases. From the simulation and a real spike in data analysis results we observed that the proposed method outperforms other methods for small-sample case in presence of outliers and it keeps almost equal performance with other robust methods (Wilcoxon, RP and FCROS) otherwise. From a head-and-neck cancer (HNC) dataset the proposed method identified 2 genes (CYP3A4, NOVA1) that are significantly enriched in linoleic acid metabolism, drug metabolism, steroid hormone biosynthesis and metabolic pathways. The survival analysis through Kaplan-Meier curve revealed that combined effect of these 2 genes has prognostic capability and they might be promising biomarker of HNC. Moreover, we retrieved the 12 candidate drugs based on gene interaction from glad4u and drug bank databases. Conclusion The identified drugs showed statistical significance and critical role of the proteins indicate that these proteins might be therapeutic target in cancer. Thus, elucidating the associations between the drugs identified in the present study require further investigations.

The emergence of the H3N2 influenza virus in 1968 marked a significant event as it crossed the species barrier. Since then, ongoing mutational dynamics have led to the formation of antigenic clusters, prompting the World Health Organization to advocate for regular updates to H3N2 vaccines. Research in the Western Pacific region underscores the necessity for heightened awareness and effective control strategies. Stemming from avian influenza A, the 1968 H3N2 influenza pandemic resulted in the deaths of one million people globally, with its seasonal variants primarily affecting older individuals and causing severe illness due to antigenic drift. To address the challenge of vaccine efficacy against H3N2 mutations, researchers are exploring innovative strategies such as precise antigenic material administration, controlled release patterns, understanding immune system mechanisms, and glycan engineering. This review comprehensively examines various aspects of the Influenza A (H3N2) virus, encompassing its virological characteristics, evolutionary trends, global epidemiology, vaccination strategies, antiviral interventions, and emerging diagnostic approaches. It underscores the impact of antigenic variation on vaccine design and effectiveness, seasonal outbreak patterns, pandemic potential, and the interplay between viral factors and host immune responses. Moreover, the review evaluates antiviral therapies and the issue of drug resistance, emphasising the necessity for multidisciplinary approaches involving researchers, healthcare professionals, and policymakers to comprehend H3N2 and enhance public health interventions.

Statins prevent cardiovascular diseases, yet their use is limited by the muscle disturbances they cause. Rarely, statin-induced myopathy is autoimmune, but more commonly it is due to direct muscle toxicity. Available evidence suggests that statin-induced creatine deficiency may be a major cause of this toxicity, and that creatine supplementation prevents it. Statins inhibit guanidinoacetate methyl transferase (GAMT), the last enzyme in the synthesis of creatine, thus they decrease its intracellular content. Such decreased content could cause mitochondrial impairment, since creatine is the final acceptor of the phosphate group of adenosine triphosphate (ATP) at the end of mitochondrial oxidative phosphorylation. Decreased cellular synthesis of adenosine triphosphate (ATP) would follow. Accordingly, ATP synthesis is decreased in statin-treated cells. In vitro, creatine supplementation prevents the opening of mitochondrial permeability transition pore caused by statins. Clinically, creatine administration prevents statin myopathy in statin-intolerant patients. Additional research is warranted to hopefully confirm these findings. However, creatine is widely used by athletes with no adverse events, and has demonstrated to be safe even in double-blind, placebo-controlled trials of elder individuals. Thus, it should be trialed, under medical supervision, in patients who cannot assume statin due to the occurrence of muscular symptoms.

Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of available structurally diverse antifungal drug armamentariums. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro antifungal activities of globospiramine against Candida albicans and Candida tropicalis and explore its possible target proteins using in silico methods. The colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid by decreasing almost 50% of the viable CFUs 60 min after treatment. Results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against C. albicans (MIC = 8 µg/mL; MFC = 4 µg/mL) and potential fungistatic effects against C. tropicalis at lower concentrations (MIC = 4 µg/mL; MFC > 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in C. albicans cells at concentrations of 16 and 8 µg/mL, which agreed with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments indicated stable, strong binding of globospiramine with the target proteins 1,3-β-glucan synthase and Als3 adhesin enzymes, which are indirectly involved in apoptotic-driven candidal inhibition.

Vaccine uptake is one of the indicators that has been used to guide immunization programs. This study aimed to evaluate whether the measles vaccine uptake is predicted by measles vaccine hesitancy. A community-based cross-sectional study was conducted in urban districts in Khartoum state in February 2019. Measles vaccine uptake among children was measured as either fully vaccinated or partially/not vaccinated. The Parents Attitude about Childhood Vaccination (PACV) scale was used to measure measles vaccine hesitancy. Multivariate logistic regression was run to identify the predictors of measles vaccination uptake controlling for sociodemographic variables and the adjusted odds ratios (aORs) with 95% CI were calculated. The receiver operator characteristic (ROC) curve was performed, besides area under the curve (AUC) for the PACV was computed. Data was collected from 495 participants. We found that measles vaccine hesitancy (PACV scores) predicted the uptake of measles vaccine after controlling other potential social confounders such as mother’s age and the number of children (aOR 1.055, 95% CI 1.028-1.028). Additionally, the ROC for the PACV yielded area under the curve (AUC 0.686 (95% CI 0.620-0.751, P <0.001). Our findings show that measles vaccine hesitancy in Sudan directly influences the uptake of the measles vaccine. Addressing the determinants of vaccine hesitancy through communication strategies will improve vaccine uptake.

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, mechanism of infection, role of angiotensin-converting enzyme 2, host defense responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants.

Meningioma (MGM) is the most common type of intracranial tumor in adults. The validation of novel prognostic biomarkers to better inform tumor stratification and clinical prognosis is urgently needed. Many molecular and cellular alterations have been described in MGM tumors over the past few years, providing a rational basis for the identification of biomarkers and therapeutic targets. The role of receptor tyrosine kinase (RTKs), including those of the ErbB family of receptors, as oncogenes has been well established in several cancer types. Here, we review histological, molecular, and clinical evidence suggesting that RTKs, including the epidermal growth factor receptor (EGFR, ErbB 1), as well as other members of the ErbB family, may be useful as biomarkers in MGM.

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.

Lung cancer is one of the most important health risks worldwide for human. Non-small cell lung cancer (NSCLC) is the most common cause of premature death from malignant disease. This study provides in-depth insights from systems biology analyses to identify molecular to inform systemic drug targeting in NSCLC. Gene expression profiles from non small cell lung cancer were analyzed with genome-scale biomolecular networks (I,e., protein-protein interaction, transcriptional and post transcriptional regulatory networks). The aim of the study was to determine the pathways and expression profile of the genes to discover molecular signature at RNA and protein levels which could serve as potential drug targets for therapeutics innovation and the identification of novel targets. Eight proteins, six TFs and seven miRNAs came into prominence as potential drug targets. The differential expression profiles of these reporter biomolecules were cross-validated by independent RNA-Seq and miRNA-Seq. Risk discrimination performance of the reporter biomolecules NPR3, JUN, PPARG, TP53, CKMT1A, SP3 and TFAP2A were also evaluated. Total 213 drugs and 7 proteins were found for non small cell lung cancer through dgidb. Among these identified drugs seven drugs such as- Gemcitabine, Carboplatin, paclitaxel, Docetaxel, Crizotinib, Bevacizumab and Gemcitabine is used for NSCLC which is approved by National Cancer Institute. The molecular signatures and repurposed drugs presented here permit further attention for experimental studies which are offer significant potential as biomarkers and candidate therapeutics for precision medicine approaches to clinical management of NSCLC.

Utility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of ≥ 70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene-expressed profiling identified significantly different neuregulin-2 (NRG2) gene expressions between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23±2.80) was significantly lower than that of controls (9.27±4.78, p < 0.001). Next, we resequenced all exons of NRG2 in other 349 ASD subjects, who were compared with super-controls from the Taiwan Biobank using case-control association analysis to determine the existence of mutations or single-nucleotide polymorphisms (SNPs). We identified three SNPs, including two noncoding ones, IVS3 + 13A > G (rs889022) and IVS9 + 32T > A (rs182642591), and one insertion/deletion (indel) SNP, named indel GCCCGGC, rs1323957797, in the NRG2 coding region. The genotype and allele frequency distribution of rs1323957797 significantly differed between ASDs and controls (p < 0.0001). Our findings showed significant differences in genotype and allele frequency distribution of the indel SNP, rs1323957797, located in the EGF-like domain region at the C-terminal of the NRG2 precursor protein. Together with our findings, the indel SNP mutation was significantly more common in ASDs than controls, leading to lower NRG2 expression than controls, influencing NRG2 function. Our study’s findings suggest that NRG2 is a susceptibility gene for ASD.

Although several carbon sequestration methods have been proposed according to theories from various disciplines, it is not known which method is the best. This study evaluated and summarized the advantage and disadvantages of several major carbon sequestration methods, including carbon capture and sequestration, ocean alkalinization, algal cultivation, and wood burial, based on the first principles, namely, sequestration scale and time, elemental stoichiometry, and energy use efficiency. This study suggested that, at present, wood burial may be a leading candidate for carbon sequestration because it can be implemented immediately on a large scale, is cost-effective and efficient, has a long sequestration time, has low technical requirements, and has a relatively low impact on agriculture. This study also discussed the implementation of wood burial from the perspective of nutrient requirements. To achieve carbon neutrality by 2050, the present study proposed a 25-year project starting in 2025 with an average sequestration rate of 3 Pg C per year, which includes burying 1.5 Pg of dead wood carbon and the creation of 9.7 × 10⁶ ha woodland.

The worldwide outbreak of SARS-CoV-2 in early 2020 caused numer- ous deaths and unprecedented measures to control its spread. We employed our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery, repurposing, and design platform to identify small molecule inhibitors of the virus to treat its resulting indication, COVID-19. Initially, few experimental studies existed on SARS-CoV-2, so we optimized our drug candidate prediction pipelines using results from two independent high-throughput screens against prevalent human coronaviruses. Ranked lists of candidate drugs were generated using our open source cando.py software based on viral protein inhibition and proteomic interaction similarity. For the former viral protein inhibition pipeline, we computed interaction scores between all compounds in the corresponding candidate library and eighteen SARS-CoV proteins using an interaction scoring protocol with extensive parameter optimization which was then applied to the SARS-CoV-2 proteome for prediction. For the latter similarity based pipeline, we computed interaction scores between all compounds and human protein structures in our libraries then used a consensus scoring approach to identify candidates with highly similar proteomic interaction signatures to multiple known anti-coronavirus actives. We published our ranked candidate lists at the very beginning of the COVID-19 pandemic. Since then, 51 of our 276 predictions have demonstrated anti-SARS-CoV-2 activity in published clinical and experimental studies. These results illustrate the ability our platform to rapidly respond to emergent pathogens and provide greater evidence that treating compounds in a multitarget context more accurately describes their behavior in biological systems.

1) Background: CFH and HTRA1 genes are traditional markers of increased risk of AMD across populations. Recent findings suggest that additional genes, for instance, in the dystrophin-associated protein complex might be promising markers for AMD. 2) Methods: Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of 134 cases with 134 unpaired controls. Cases were 60 years or older (CARMS grade 4-5, as assessed by experienced ophthalmologists following the AAO guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or RPE changes on fundus exam and negative family history of AMD. We examined SNPs in the SGCD gene: rs931798, rs140617, rs140616, and rs970476 by sequencing and RT-PCR. Genotyping quality check and univariate analyses were performed with PLINK v.1.9. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. 3) Results: After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% (1.81, 95%CI 1.06-3.14, p=0.031), especially the geographic atrophy phenotype (1.82, 95%CI 1.03-3.21, p=0.038) compared to the G/G homozygous. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (Adjusted OR 0.13, 95%CI 0.02-0.91, p=0.041). 4) Conclusions: SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted.

Owing to the rising demand for vegetable soybean products, there is an increasing need for high-yield soybean varieties to raise the output. However, complex correlation patterns among quantitative traits with genetic interactions bring a challenge for vegetable soybean breeding. Here, a genome-wide association study (GWAS) was applied for six yield-related traits with 188 vegetable soybean accessions. A total of 81 SNPs were identified for pod length, plant height, pods number, pod thickness, pod width, and seed weight per plant by Blink model. Among these significant SNPs, 79 were novel SNPs, while 2 overlapped with previously reported SNPs. A total of 220 genes were found in 100 kb upstream and downstream regions of significant SNPs, of which 17 genes were functional proteins. Among these function proteins, four candidate genes, Glyma.13G109100, Glyma.03G183200, Glyma.09G102200, and Glyma.09G102300 were analyzed as significant haplotype variations, which encode MYB-related transcription factor, auxin-responsive family protein, F-box protein and CYP450, respectively. In addition, the relative expression with four candidate genes in the V030 and V071 (Among them, the plant height, pod number and fresh pod weight of V030 were lower than V071 strains) vegetable soybean were significantly different and these genes could be involved in plant growth and development via various pathways. Therefore, we proposed four genes from vegetable soybean germplasm that could be the key candidate genes for pod yield and plant height and these studies will accelerate the process of high-yield vegetable soybean breeding.

Vaccination is widely regarded as a cornerstone in animal or herd health and infectious disease management. Nineteen vaccines against the major pathogens implicated in bovine respiratory disease are registered for use in the UK by the Veterinary Medicines Directorate (VMD). However, despite annual prophylactic vaccination, bovine respiratory disease is still conservatively estimated to cost the UK economy approximately £80 million per annum. This review examines the vaccine types available, discusses the surrounding literature and scientific rationale of the limitations and assesses the potential of novel vaccine technologies.

Coronavirus disease 2019 (COVID-19) has been first appeared in Wuhan, China but its fast transmission, led to its widespread prevalence in various countries and make it a global concern. In addition, lack of a definitive treatment is another concern that needs to be attention. Researchers have come up with several options, which are not certain, but protease inhibitor and some antiviral agent are in the forefront. In this study a virtual screening procedure employing docking of different databases including 1615 FDA approved drugs was used to identify new potential small molecule inhibitors for protease protein of COVID-19. The docking result indicates that among all, simeprevir (Hepatitis C virus (HCV) NS3/4A protease inhibitor) could fit well to the binding pocket of protease and because of some other positive features including ADME profile, might be a helpful treatment option for COVID-19.

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.

Background: This study aimed to evaluate whether measles vaccine uptake can be predicted directly or indirectly by parental perceptions about the availability of measles vaccine services with parental hesitancy towards the measles vaccine as a potential mediator. Methods: This was a community-based cross-sectional study conducted at Omdurman locality in Khartoum state, Sudan in February 2019. The study population included parents/ guardians having at least one child aged 2 -3 years old. Mediation analysis was conducted using two models, the ordinary least squares path analysis and multiple logistic regression. Results: a total of 495 responded and the mean age of the mothers who participated in the study was 31.1 (SD=5.73). A half of the respondents (50.1%) completed university education and nearly three-quarters of the respondents (74.7%) were housewives. After controlling for the other factors, including the mother’s age and the number of children, parental perception about the accessibility and availability of the measles vaccine influences the uptake of the measles vaccine indirectly through the mediation effect of measles vaccine hesitancy. Conclusions: We suggest that intervening in measles vaccine hesitancy in addition to measles vaccination access issues will have positive impact on the uptake and coverage of the measles vaccine in Sudan.

The study focuses on the crucial aspect of lossless compression for FAST pulsar search data. The deep generative model PixelCNN, stacking multiple masked convolutional layers, achieves neural network autoregressive modeling, making it one of the most excellent image density estimators. However, the local nature of convolutional networks causes PixelCNN to concentrate only on nearby information, neglecting important information at greater distances. Although deepening the network can broaden the receptive field, excessive depth can compromise model stability, leading to issues like gradient degradation. To address these challenges, the study combines causal attention modules with residual connections, proposing the Causal Residual Attention Module to enhance the PixelCNN model. This innovation not only resolves convergence problems arising from network deepening but also widens the receptive field. It effectively utilizes global features, particularly capturing vertically correlated features prominently present in subgraphs of candidates. This significantly enhances its capability to model pulsar data.In the experiments, the model is trained and validated using the HTRU1 dataset. The study compares the average negative log-likelihood score with baseline models like GMM, STM, and PixelCNN. The results demonstrate the superior performance of the our model over other models. Finally, the study introduces the practical compression encoding process by combining the proposed model with arithmetic coding.

Cameroon introduced the malaria vaccine in its routine immunization programme on 22 January 2024, in the 42 districts out of 200, among the most at risk of malaria. A cross-sectional analysis of data on vaccine key events in the introduction roadmap and vaccine uptake during the first 30 days was conducted. In addition to available gray literature related to the introduction of the malaria vaccine, data on malaria vaccine uptake by vaccination session, collected through a digital platform, were analyzed. A total of 1,893 reports were received from 22 January 2024 to 21 February 2024 from 766 health facilities (85% of overall completeness). Two regions out of 10 recorded less than 80% of completeness. As of 21 February 2024, 13,811 children have received the first dose of the malaria vaccine, including 7,124 girls (51.6%) and 6,687 boys (48.4%). Thirty six percent of children were vaccinated through outreach sessions versus 61.5% through sessions in fixed posts. The overall monthly immunization coverage with the first dose was 37%. Early results have shown positive attitudes towards and acceptance of malaria vaccines. Suboptimal completeness of data reporting and low coverage highlight persistent gaps and challenges in vaccine rollout.

Background In 2016, Global Polio Eradication Initiative (GPEI) recommended cessation of type 2 oral poliovirus vaccine (OPV) and OPV using countries switched from trivalent to bivalent OPV (bOPV) with addition of inactivated poliovirus vaccine (IPV) in the routine immunization schedule. The current GPEI strategy 2022-2026 includes bOPV cessation plan and switching to IPV standalone or the combination vaccine schedules in future. The focus of our study was to evaluate immunogenicity of monovalent OPV type 1 (mOPV1) with IPV and IPV only schedules. Methods This was a three-arm, multi-center randomized controlled trial conducted in 2016-2017 in India. Participants, at birth, were randomly assigned to bOPV-IPV (Arm A) or mOPV1-IPV (Arm B) or IPV (Arm C) schedules. Serum specimens collected at birth, 14-, 18- and 22- weeks age were analyzed with standard microneutralization assay for all three poliovirus serotypes. Results Results of 598 participants were analyzed. The type 1 cumulative seroconversion rates four weeks after completion of the schedule at 18 weeks were 99.5% (97.0-99.9), 100.0% (97.9-100.0) 96.0% (92.0-98.1) in Arms A (4bOPV+IPV), B (4mOPV1+IPV) and C (3IPV) respectively. Type 2 and type 3 seroconversion at 18 weeks were 80.0% (73.7-85.1), 76.9% (70.3-82.4), 93.2% (88.5-96.1) and 100.0% (98.0-100.0), 81.9% (75.6-86.8), 99.4% (96.9-99.9) respectively in the three arms. Conclusions This study shows high efficacy of different polio vaccines for serotype 1 in all three schedules. Type 1 seroconversion rate of mOPV1 is non-inferior to bOPV. All the vaccines provide high type specific immunogenicity. The program can adopt the use of different vaccines or schedules depending on epidemiology from time-to-time.

Background/Aim: In clinical practice, uterine lipoleiomyomas are variants of uterine leiomyomas, often found incidentally, and do not require surgical treatment unless patient’s symptomatic. Therefore, these should be clinically differentiated from lesions that need surgical treatment. Conversely, hemangiomas, or blood vessel benign tumors, rarely develop in the uterus; however, many clinical complications such as abdominal pain and excessive vaginal bleeding result from a uterine hemangioma. Hemangiomas can occur at any age and primarily affect pregnant women. Materials and Methods: The oncological properties of uterine lipoleiomyoma and hemangioma in adults were investigated using molecular pathological examination on tissue excised from patients with uterine leiomyoma. Results: Through molecular pathological studies, which included potential biomarkers for uterine mesenchymal tumors, a differential diagnosis was established for this case of mesenchymal tumor. Herein, we report a 54-year-old non-pregnant woman who presented with vaginal bleeding and underwent hysterectomy after detection of a 140 × 100 mm intramural mass diagnosed as a concurrent uterine hemangioma and lipoleiomyoma after molecular histopathologic examinations. Conclusion: As far as we know, this case is the first patient of concurrent uterine hemangioma and lipoleiomyoma. Hence, such occurrence of several types of mesenchymal tumors must be considered in the differential diagnosis of patients with abnormal vaginal bleeding.

Mitochondrial Encephalohepatopathy (MEH) is an autosomal recessive neurodevelopmental disorder usually accompanied by microcephaly, white matter changes, cardiac and hepatic failure. Here, we applied the whole-exome sequencing (WES) framework on a trio family data with unaffected non-consanguineous parents and proband (neonate girl) with this inherited disorder. A total of 2,928,402 variants were observed with 2,613,746 SNPs, 112,336 multiple nucleotide polymorphisms (MNPs), 72,610 insertions, 113,207 deletions and 16,503 mixed variants. These variations are responsible for 82,813,631 effects on various genomic regions. Our pipeline uncovered candidate gene mutations from these variants and retained a handful of 5,277 variants harboring 3,598 genes, out of which, 8 genes codes for non-coding RNA while 178 genes are those with high impact severity. Among these 178 variants, 125 are de-novo variants that are not previously reported in the ClinVar database. Consistent to previous studies, the leftover high impact severity genes are involved in encephalopathy, Leigh syndrome, Charcot–Marie–Tooth disease, global developmental disorder, seizures, spastic paraplegia, premature ovarian failure, mitochondrial myopathy-cerebellar, ataxia-pigmentary, retinopathy syndrome, ocular and retinal degeneration, deafness, intellectual disability, cardiofacioneurodevelopmental syndrome etc. All these clinical features were also observed in the patient studied. The current analysis highlights and expands the genetic architecture of the MEH phenotype. Furthermore, this pipeline on trio family data significantly broadens the concept of its usefulness as a first-tier diagnostic method in the detection of complex multisystem phenotypic disorders.

Genome-wide association studies have revealed a locus at 8p12 that is associated with breast cancer risk. Fine-mapping of this locus identified 16 candidate causal variants (CCVs). However, as these variants are intergenic, their function is unclear. To map chromatin looping from this risk locus to a previously identified candidate target gene, DUSP4, we performed chromatin conformation capture analyses in normal and tumoral breast cell lines. We identified putative regulatory elements, containing CCVs, that loop to the DUSP4 promoter region. Using reporter gene assays, we found that the risk allele of CCV rs7461885 reduced the activity of a DUSP4 enhancer element, consistent with the function of DUSP4 as a tumor suppressor gene. Furthermore, the risk allele of CCV rs12155535, located in another DUSP4 enhancer element, was negatively correlated with looping of this element to the DUSP4 promoter region, suggesting that this allele would be associated with reduced expression. These findings provide the first evidence that CCV risk alleles downregulate DUSP4 expression, suggesting that this gene is a regulatory target of the 8p12 breast cancer risk locus.

The phenomenon of vaccine hesitancy is a growing threat to public health with far-reaching implications. The widening gap between the vaccinated and the proportion needed for herd immunity raises two critical research questions that are of interest to practitioners, researchers, and policymakers: (1) What determines one’s decision to be vaccinated? and (2) What is the implication of COVID-19 vaccine hesitancy on economic recovery? In this study, we use empirical data in the context of South Africa to investigate factors affecting COVID-19 vaccine hesitancy and their implications for economic recovery. Findings reveal key socio-demographic and institutional drivers of COVD-9 vaccine hesitancy, which include age (the youth are more hesitant), inadequate information on the vaccine (those who perceive they have adequate information are vaccinated), trust issues in government institutions, conspiracy beliefs, vaccine-related factors, and perceived side effects associated with the vaccine. Additionally, an individual’s decision to remain hesitant about COVID-19 vaccination has implications for businesses and the economy by limiting movement and trade, increasing unemployment, and causing a resurgence of new variants. Based on the findings, action plans such as information dissemination, convenience vaccination centers, consistency communications, and targeted campaign strategies are recommended for improving vaccine intakes and a positive economic recovery.

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.

Stalk rot caused by Fusarium fungi is one of the most widespread and devastating diseases of maize, and the introduction of resistant genotypes is one of the most effective strategies for controlling the disease. Breeding genotypes with genetically determined resistance will also allow less use of crop protection products. The aim of the research was to identify molecular markers and associated candidate genes determining maize plant resistance to Fusarium stalk rot. The plant material for the study consisted of 122 maize hybrids, which were sown in plots of 10 m2, in a complete randomized block design, in three repetitions, at two locations (Smolice: 51 42’ 58.904’’ N, 17 13’ 29.13’’ E and Kobierzyce: 50 58’ 19.411’’ N, 16 55’ 47.323’’ E). The analyzed genotypes were simultaneously subjected to next-generation sequencing using the Illumina platform. The results of the observation of the degree of infection and sequencing were used for association mapping, which ultimately resulted in the selection of 10 molecular markers important at both places. Among the identified markers, two SNP markers that are located inside candidate genes play an important role. Marker 4772836 is located inside the serine/threonine-protein kinase bsk3 gene, while marker 4765764 is located inside the histidine kinase 1 gene. Both genes can be associated with plant resistance to Fusarium stalk rot, and these genes can also be used in breeding programs to select resistant varieties.

Enzymatic hydrolysis of bovine and human hemoglobin yields a diversity of bioactive peptides, some of which are recognized for their antimicrobial properties. Certain small antimicrobial and anticancer peptides target protein synthesis inhibition. This study aims to produce bioactive peptides through enzymatic hemoglobin hydrolysis and evaluate their effects on cell growth inhibition, potentially serving as candidates for biological anticancer drugs. Rapid screening of candidate anticancer peptides derived from enzymatic hydrolysis of bovine and human hemoglobin was conducted using the Lepidium sativum radicle growth technique. The results demonstrate that: 1) the degree of hydrolysis (DH) significantly influences the production of bioactive peptides. DH levels of 3-10% yield considerably stronger radicle growth inhibition compared to DH 0 (native hemoglobin form), exhibiting three to four times greater intensity. 2) Certain peptide fractions from bovine hemoglobin exhibit higher activity than those from human hemoglobin. 3) The structural characteristics of peptides play a crucial role in the observed biological effects. 4) The α137-141 peptide is the most active among the fractions obtained from bovine (IC₅₀ = 29 ± 1 µg/mL) and human hemoglobin (IC₅₀ = 48 ± 2 µg/mL), standing out 10 to 15 times more potent than other hemoglobin fractions. In conclusion, these findings affirm the bioactivity of peptide fractions obtained from bovine and human hemoglobin. The study highlights how enzymatic hydrolysis of bovine and human hemoglobin can yield peptides that inhibit protein synthesis. Ultimately, these results suggest the feasibility of obtaining candidate peptides for biological anticancer drugs from both human and bovine hemoglobin sources. These scientific advances show new hope in the fight against cancer which affects a large number of people around the world.

The aim of present study was to link the gene expression profile of selected candidate genes with blood profile, growth performance and carcass traits of Barki lambs. Thirty-eight Barki lambs were divided into 3 groups (fast, intermediate and slow growing) according to growth perfor-mance. Body tissues (muscle, liver and fat) were taken from for RNA isolation and Real-time PCR. The results indicated that, the final body weight hot carcass weight were heavier (P ≤ 0.05) in fast (49.9 Kg and 24.57) than intermediate (40.7 and 19.07 Kg) and slow (30.8 and 15.10 Kg) growing animals. The blood profile of total protein, total lipids, calcium, T3 and T4 hormones did not differ among sheep groups. Genes involved in protein biosynthesis (RPL7), fatty acid oxidation (CPT1) and lipolysis (FABP4) were up regulated in fast and intermediate growing lambs in all studied tissues. While, gene-regulating lipogenesis (ADIPOQ) was expressed simi-larly in fat and liver tissues, but increased its expression in muscle of fast and intermediate growing lambs. Expression of CAPN3 was increased in fast and intermediate growing compared to slow growing lambs. In conclusion, the current study providing an evidence for the im-portance of co-expression of these genes in main body tissues linked with growth performance of Barki lambs.

Background and objectives: Colorectal cancer (CRC) is the second most common cause of cancer-related death in the world, but early diagnosis ameliorates the survival of CRC. This report directed to identify molecular biomarker signatures in CRC. Materials and Methods: We analyzed two microarray datasets (GSE35279 and GSE21815) from Gene Expression Omnibus (GEO) to identify mutual differentially expressed genes (DEGs). We integrated DEGs with protein-protein interaction and transcriptional/post-transcriptional regulatory networks to identify reporter signaling and regulatory molecules; utilized functional overrepresentation and pathway enrichment analyses to elucidate their roles in biological processes and molecular pathways; performed survival analyses to evaluate their prognostic performance; and applied drug repositioning analyses through Connectivity map (CMap) and geneXpharma tools to hypothesize possible drug candidates targeting reporter molecules. Results: A total of 727 up-regulated and 99 down-regulated DEGs were detected. The PI3K-Akt signaling, Wnt signaling, ECM-interaction, and cell cycle were identified as significantly enriched pathways. Ten hub proteins (ADNP, CCND1, CD44, CDK4, CEBPB, CENPA, CENPH, CENPN, MYC, and RFC2), 10 transcription factors (ETS1, ESR1, GATA1, GATA2, GATA3, AR, YBX1, FOXP3, E2F4, and PRDM14) and 2 miRNAs (miR-193b-3p and miR-615-3p) were detected as reporter molecules. The survival analyses through Kaplan Meier curves indicated remarkable performance of reporter molecules in estimation of survival probability in CRC patients. In addition, several drug candidates including anti-neoplastic and immunomodulating agents were repositioned. Conclusions: This study presents biomarker signatures at protein and RNA levels with prognostic capability in CRC. We think that the molecular signatures and candidate drugs presented in this study might be useful in future studies indenting development of accurate diagnostic and/or prognostic biomarker screens and efficient therapeutic strategies in CRC.

Schistosomiasis, a disease historically associated with poverty, lack of sanitation and social inequalities, is a chronic, debilitating parasitic infection, affecting hundreds of millions of people in endemic countries. Although schistosomiasis control approach has shown that chemotherapy is capable of reducing morbidity in humans, rapid re-infection is a reminder that the impact of drug treatment on transmission control or elimination initiatives is marginal. In addition, and regardless of more than two decades of well-executed control activities based on large-scale chemotherapy, the disease is expanding in many areas including Brazil. The development of the Sm14/GLA-SE schistosomiasis vaccine is an emblematic open knowledge innovation that has successfully completed Phase I and Phase IIa clinical trials, with Phase II/III trials underway in the African continent and to be followed in Brazil. Discovery and experimental phases were long term achievements leading to a robust collection of data that are strongly supporting the presently ongoing Clinical Phase. This paper reviews the development of the Sm14 vaccine formulated with GLA-SE (Glucopyranosyl Lipid A), from the earlier experimental developments to clinical trials including the recent status of Phase II studies.

The worldwide competition to vaccinate against COVID-19 has highlighted the importance of immunization measures in containing the virus. Saudi Arabia, like the rest of the globe, must assess socio-demographic subtleties, chronic illnesses, vaccination effects, and public health policy implications as it navigates this complicated environment. This cross-sectional study examined Saudi COVID-19 vaccine in many ways. It examined the socio-demographic makeup of vaccine recipients, the prevalence of chronic conditions in this population, vaccine administration patterns, post-vaccination side effects, and vaccine-infection rates. A questionnaire-based online survey of 401 participants ensured gender, nationality, age, weight, and educational diversity. We analyzed vaccine manufacturer choice for each dosage, side effects after the first and second doses, and chronic diseases in the sample. Pfizer/BioNTech vaccines are preferred for all three doses, reflecting worldwide vaccination acceptance patterns. Side effects were not significantly different between vaccination kinds. Interestingly, immunization reduced infection rates, demonstrating the efficacy of COVID-19 vaccines. The data fills important information gaps and illuminates Saudi COVID-19 vaccination kinetics. These data support the global preference for mRNA vaccines, demonstrating the faith in this breakthrough technology. They also sponsor COVID-19 vaccine safety and effectiveness studies. The dramatic drop in infection rates among vaccinated people shows how vaccinations suppress the pandemic. These findings inform Saudi Arabia's immunization efforts. As booster doses become more common, long-term vaccination research is crucial. Vaccine reluctance, especially in certain demographics, must be addressed. Due to vaccines' protective potential, equitable vaccine distribution and large immunization programs are essential for herd immunity and pandemic management. This thorough cross-sectional study helps policymakers and healthcare practitioners build successful and inclusive COVID-19 immunization regimens in Saudi Arabia.

Durum wheat is an economically and nutritionally important cereal. The increase in durum wheat yield is mostly associated with improving grain traits. The grain size and shape-related traits are directly related to wheat yield. In addition, grain size influences the seed germination rate and seedling vigour, which play key roles in stand establishment and yield. Thus, it is important to investigate grain traits both agro-morphologically and genetically. In this study, a panel of durum wheat, consisted of 146 genotypes, was evaluated for grain traits agro-morphologically, and a genome-wide association study (GWAS) was conducted to dissect the genomic regions associated with these traits. As a result of GWAS, a total of 41 marker-trait associations (MTAs) were identified on different chromosomes of durum wheat. Of these MTAs, only 11 were stable across environments. A BLAST search for flanking sequences of every stable MTAs in the Svevo genome identified 18 putative candidate genes directly associated with seed traits of different plants, particularly wheat seeds. In conclusion, the annotation results and literature information provide strong evidence that identified stable MTAs and their candidate genes may have important functions in the formation of wheat grain traits. After the validation of these MTAs with different fine-mapping and functional characterization studies, these loci may provide valuable information for geneticists and breeders to improve wheat yield.

Horizontal gene transfer (HGT) is the transmission of genes between organisms by other means than parental to offspring inheritance. While it is prevalent in prokaryotes, HGT is less frequent in eukaryotes and particularly in metazoan. Here, we propose Alienness, a taxonomy-aware web application that parses BLAST results against public libraries to rapidly identify candidate HGT in any genome of interest. Alienness takes as input the result of a BLAST of a whole proteome of interest against any NCBI protein library. The user defines recipient (e.g. metazoan) and donor (e.g. bacteria, fungi) branches of interest in the NCBI taxonomy. Based on the best BLAST E-values of candidate donor and recipient taxa, Alienness calculates an Alien Index (AI) for each query protein. An AI >0 indicates a better hit to candidate donor than recipient taxa and a possible HGT. Higher AI represent higher gap of E-values between candidate donor and recipient and a more likely HGT. We confirmed the accuracy of Alienness on phylogenetically confirmed HGT of non-metazoan origin in plant-parasitic nematodes. Alienness scans whole proteomes to rapidly identify possible HGT in any species of interest and thus fosters exploration of HGT more easily and largely across the tree of life.

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprising of killed, inactivated, or live attenuated pathogens have resulted in protective immune responses, negative consequences of their administration have been well-appreciated. Modern vaccines have evolved to contain purified antigenic proteins, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to modern vaccine platforms. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present repetitive array of antigens for improving immunogenicity and enhancing protective responses. Discovery and characterization of naturally occurring PNPs from various living organisms such as bacteria, archaea, viruses, insects, and eukaryotes, as well as computationally designed structures and approaches to link antigens to the PNPs have paved the way for unprecedented advances in the field of vaccine technology. In this review, we focus on some of the widely used naturally occurring and optimally designed PNPs for their suitability as promising vaccine platforms for displaying native-like antigens from viral pathogens for protective immune responses. Such platforms hold great promise in combating emerging and re-emerging infectious diseases and enhancing vaccine efficacy and safety.

Traditional vaccines are produced by using weakened or inactivated forms of disease-causing pathogens to produce the target antigen they are designed to protect against. Messenger RNA vaccines are a class of vaccines that employ a minute segment of genetic material, known as messenger RNA (mRNA), which contains directives for the cells in the body to generate a particular protein. This genetic material is synthesized in the laboratory and packaged into a lipid nanoparticle, which protects and helps it enter cells for further protein synthesis. During vaccination with mRNA vaccine, the lipid nanoparticles containing the mRNA are injected into the muscle of vaccinees. Once inside the cells, the mRNA instructs the cells to produce a protein which is then displayed on the surface of the cell, triggering an immune response. During this, the immune system recognizes the displayed protein as foreign and mounts a defense by producing antibodies and activating immune cells to target and eliminate the protein. Furthermore, these immune responses generate a memory cell, facilitating the immune system to promptly react in case of encountering the authentic pathogen as an infection in the future. The mRNA vaccines are flexible and the sequence can be easily synthesized in the lab based on the genetic information of the target pathogen. Additionally, mRNA vaccines can be developed for new strains or variants of the target disease easily. This was particularly evident during the COVID-19 pandemic, where mRNA vaccines like the Pfizer-BioNTech and Moderna vaccines were developed and authorized for emergency use within a year. But currently, available mRNA vaccines require extensive cold chain, antigen delivery, potential immune response variability optimization, and sophisticated manufacturing process. The efforts to explore next-generation mRNA vaccine development are aimed to further improve the effectiveness, stability, and delivery methods. One focus of research has been to enhance the stability of mRNA vaccines, particularly temperature sensitivity which makes storage and distribution easier, particularly in regions with limited access to cold chain infrastructure. Self-amplifying mRNA vaccines, on the other hand, are designed to generate multiple copies of the mRNA within cells which potentially leads to a higher production of the target protein, resulting in a stronger immune response. Additionally, studies are exploring new delivery systems to improve the target and efficiency of mRNA vaccines using specialized nanoparticles and liposomes to specifically deliver mRNA to certain cell types or immune cells. Another area of interest is the development of combination vaccines, where multiple mRNA sequences are included in a single vaccine protecting against multiple diseases targeting strains or variants of a particular pathogen simultaneously. While current mRNA vaccines are administered via intramuscular injection, studies are underway to deliver directly into the skin offering enhanced immune response and the ability to use smaller vaccine doses.

Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.

The Bacillus Calmette-Guérin (BCG) vaccine has been used for over one hundred years to protect against the most lethal infectious agent in human history, tuberculosis. Over four billion BCG doses have been given and, worldwide, most newborns receive BCG. A few countries, including the United States, did not adopt the WHO recommendation for routine use of BCG. Moreover, within the past several decades, most of Western Europe and Australia, having originally employed routine BCG, have discontinued its use. This review article articulates the impacts of those decisions. The associated consequences include increased tuberculosis, increased infections caused by non-tuberculous mycobacteria (NTM), increased autoimmune disease (autoimmune diabetes and multiple sclerosis) and increased neurodegenerative disease (Parkinson’s disease and Alzheimer’s disease). This review also offers an emerged zoonotic pathogen, Mycobacterium avium ss. paratuberculosis (MAP) as a mostly unrecognized NTM that may have a causal role in some, if not all, of these diseases. Current clinical trials with BCG for varied infectious, autoimmune and neurodegenerative diseases have brought this century-old vaccine to the fore due to its presumed immuno-modulating capacity. With its historic success and strong safety profile, the new and novel applications for BCG may lead to its universal use –putting the Western World back onto the road not taken.

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

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.

Ningxiang pigs exhibit a diverse array of fatty acids, making them an intriguing model for exploring the genetic underpinnings of Fatty acid metabolism. In this study, we conducted a genome-wide association study using a dataset comprising 50,697 SNPs and samples from over 600 Ningxiang pigs. Our investigation yielded novel candidate genes linked to five saturated fatty acids (SFAs), four monounsaturated fatty acids (MUFAs), and five polyunsaturated fatty acids (PUFAs). Re-markably, 37, 21, and 16 SNPs showed significant associations with SFAs, MUFAs, and PUFAs, respectively. Notably, ALGA0047587, H3GA0046208, DRGA0016063, and ALGA0031262 demonstrated substantial phenotypic variance (≥ 30%) in Arachidic acid (C20:0), Elaidic Acid (C18:1n-9(t)), and Arachidonic acid (C20:4n-6), respectively. Several significant SNPs were posi-tioned proximally to previously reported genes. In total, we identified 11, 6, and 5 candidate genes associated with SFAs, MUFAs, and PUFAs, respectively. These findings hold great promise for advancing breeding strategies aimed at optimizing meat quality and enhancing lipid metabolism within the intramuscular fat (IMF) of Ningxiang pigs.

Rapeseed (Brassica napus) is one of the most important oil crops in the world; however, drought significantly curtails its growth and productivity. Identifying drought-tolerant germplasm is an efficient and low-cost strategy for addressing water shortages. Using water loss ratio (WLR) as an index of drought tolerance, we screened a panel of 265 B. napus lines. We identified eight low-WLR and six high-WLR accessions, which were regarded as drought-tolerant and drought-sensitive, respectively. Further validated these selected accessions at the seedling stage under drought-stress conditions. The drought-tolerant accessions had significantly greater fresh and dry weights under drought stress than the drought sensitive accessions. Using RT-qPCR, we showed that a set of previously reported drought-adaptive marker genes were expressed at higher levels in the drought-tolerant lines than in the drought-sensitive lines. These results indicated that the drought-tolerant genotypes could be identified from natural populations using WLR. Then, we performed a genome-wide association study to identify loci harboring single nucleotide polymorphisms (SNPs). A total of 139 SNPs were significantly associated with the WLR, of which chromosome A10 harbored the largest number. Furthermore, four putative candidate genes were selected by combining the SNP–WLR association results and transcriptional expression data with the changes in drought tolerance. Thus, we have identified two drought-tolerant B. napus cultivars and uncovered genome-wide variation differentiating B. napus lines related to WLR, in addition to providing insights for further research into WLR-related drought mechanisms.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

: Background: Vaccination against COVID-19 has been the main strategy used by most countries to limit the spread of the virus. However, vaccine uptake has been low in Africa, leading to the implementation of several interventions in order to improve vaccine coverage. This study was conducted due to the lack of information about COVID-19 vaccine coverage and the factors associated with vaccine hesitancy. Methods: This cross-sectional study was carried out in Kinshasa city using multi-stage random sampling. A total of 2160 households were included in the study. The data were analyzed using Stata 15 software. The means and standard deviations were calculated for normally distributed continuous variables, while proportions with their 95% confidence intervals (CIs) were calculated for categorical variables. Pearson’s chi-square test or Fisher’s exact test was used to test the associations between dependent variables and each independent variable. Logistic regression was used to identify the factors associated with hesitancy receiving the COVID-19 vaccination. Results: The majority of respondents were aged between 25 and 34 and 35 and 49 (28.9%). During this study, 15% (95% CI [13.25–17.9]) of respondents had received at least one dose of the COVID-19 vaccine. Among the reasons given for refusing to be vaccinated, most respondents cited concerns about the vaccine being unsafe or causing adverse reactions (45%). Among the reasons given for accepting the vaccine, 26% thought that the vaccine prevented superinfection. The factors associated with hesitancy toward the COVID-19 vaccine were female gender, an age of less than 35 years, and living in non-slum households. Conclusions: Despite the interventions implemented across the country, the reluctance to be vaccinated remains a problem; this could lead to poor health outcomes, especially among the elderly and those with pre-existing conditions. It is important to step up awareness-raising campaigns in the community in order to increase the uptake of vaccination.

The Hepatitis B virus, chronically infects over 240 million persons worldwide. The Hepatitis B vaccine is 90% effective in preventing perinatal transmission if the first dose is given within the first 24 hours of life followed by a minimum of 2 subsequent doses. In October 2021, Antigua and Barbuda, through it’s only public hospital - the Sir Lester Bird Medical Centre, instituted a hospital based Hepatitis B vaccine birth dose policy. Timely birth dose coverage was 72% and total birth dose coverage 81%. 10.5% of parents refused the hepatitis b – birth dose, of which 76% either felt uncomfortable or preferred to wait. 100% of babies born before arrival received timely vaccine administration, likewise 100% of Hepatitis B exposed babies were vaccinated, with 83% of them receiving the Hepatitis B Immunoglobulin. A maternal Hepatitis B surface antigen result was available for 90.4% of mothers. Barriers to timely birth dose administration included vaccination hesitancy, gaps in healthcare worker knowledge, and the consistent supply of Hepatitis B vaccine. Instituting a quality improvement team, health information system, robust educational efforts, and addressing barriers will make achieving the WHO programmatic targets of eliminating mother to child transmission of hepatitis B by 2030 possible.

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain, which has naturally high pathogenic properties for mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity also in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced. SA-M5 lost E358E/K heterogeneity and retained E358, which is the prevalent amino acid at this position among H1N1pdm09 strains. Besides, in the hemagglutinin of SA-M5, two heterogeneous substitutions (G155G/E and S190S/R) were identified. Both viruses, SA-M5 and SA-WT, were compared for their toxicity, ability to replicate, pathogenicity, and immunogenicity for mice. In mice infected with SA-M5 or SA-WT strains, toxicity, virus titer in pulmonary homogenates, and mouse survival did not differ significantly. Contrarily, an increase in the immunogenicity of SA-M5 compared to SA-WT was observed. This increase could be due to the substitutions G155G/E and S190S/R in the HA of SA-M5. The prospects for using SA-M5 in studying the immunogenicity mechanisms were also discussed.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic in 2020, following which a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, it has been reported worldwide that the modified mRNAs encoding spike proteins and lipid nanoparticles, which are used as drug delivery systems, not only cause thrombosis and cardiovascular disorders post vaccination, but might also cause diverse diseases involving all organs and systems, including the nervous system. Furthermore, the toxicity and pathogenicity of spike proteins may necessitate defining these proteins as nonbiological infective material. Based on these reports and the abundant evidence that has come to light in the past few years, this paper aims to draw the attention of medical professionals to the various risks associated with transfusion using blood products derived from long COVID patients or from genetic vaccine recipients, and to make proposals regarding specific inspection items, testing methods, regulations, etc. This paper provides insights to address the post-vaccination syndrome and its consequences following such genetic vaccination programs.

Metal nanoframes have gained tremendous attention in the domain of modern research and development due to their distinctive 3D spatial structure, efficient physiochemical properties, and comparatively good activity. Different strategies have been implicated by the researchers to design nano frame of varying chemical nature and shapes. Most of the synthetic protocols being adopted to design a nano framee, mainly consist of two main steps, nucleation and growth of solid particles and secondly excavation of the interiors. In this context, many synthetic methods are overviewed. To show their unprecedented performance or activity, a few applications in catalytic, biomedical, theranostic, SERS, sensing of different materials, reduction of CO2, etc are also discussed.

Recently, a database of human piRNAs has been created, which allows studying the binding of many piRNAs to mRNAs of genes involved in many diseases, including cancer. In the present work, we investigated what piRNAs can interact with candidate esophageal squamous cell carcinoma (ESCC) genes. The binding of 480 thousand piRNAs with mRNAs of 66 candidate ESCC genes was studied. Bioinformatic studies found that piRNAs bind only to the mRNAs of nine candidate genes: AURKA, BMP7, GCOM1, ERCC1, MTHFR, SASH1, SIX4, SULT1A1, and TP53. It has been shown that piRNAs can bind to mRNA by overlapping nucleotide sequences in limited 3'UTR and 5'UTR regions called clusters of binding sites (BSs). The existence of clusters of piRNA BSs significantly reduces the proportion of nucleotide sequences of these sites in the mRNA of target genes. Competition between piRNAs occurs for binding to the mRNA of target genes. Individual piRNAs and groups of piRNAs that have separate BSs and clusters of BSs in the mRNAs of two or more candidate genes have been identified in the mRNAs of these genes. This organization of piRNAs BSs indicates the interdependence of the expression of candidate genes through piRNAs. Significant differences in the ability of genes to interact with piRNAs avoid the side effects of piRNAs on genes with the lack of binding of such piRNAs. Individual piRNAs and sets of piRNAs are proposed and recommended for the diagnosis and therapy of ESCC.

The excessive use of synthetic insecticides in modern agriculture has led to the contamination of the environment and the development of insect resistance. In this study, we evaluated the potential of tangerine (Citrus reticulata L.) peel essential oil (EO) as a natural insecticide against greenhouse whitefly (Trialeurodes vaporariorum W. (Homoptera: Aleyrodidae)), a common pest in greenhouse production. Petroleum ether (PET) and n-hexane (HEX) were used as solvents to extract essential oil (EO) from tangerine peels. The yield of EO was 1.59 % and 2.00 % (m/m) for PET and HEX, respectively. The insecticidal activity of EO was evaluated by measuring the mortality rate (MR) of greenhouse whiteflies at different time intervals. The results showed that PET and HEX extracts of tangerine EO effectively controlled the greenhouse whitefly. With both solvents, it was observed that with doses of 12.5% (v/v), similar results were achieved as with the positive control (corresponding to the commercial insecticide imidacloprid). Additionally, the FTIR analysis found that the EO contained d-limonene, which may be the source of its insecticidal properties. Therefore, tangerine peel essential oil is an excellent natural insecticide candidate for controlling greenhouse whiteflies effectively and sustainably.

Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Delayed cancer detection is one of the common causes of poor prognosis in case of many cancers including the cancers of the oral cavity. Despite improvement and development of new and efficient gene therapy treatments, very little has been done to algorithmically assess the impedance of these carcinomas. In this work, we attempt to annotate viable attributes in oral cancer gene datasets for identification of gingivobuccal cancer (GBC). We further apply supervised and unsupervised machine learning methods to the gene datasets revealing key candidate attributes for GBC prognosis. Our work highlights the importance of automated identification of key genes responsible for GBC that could perhaps be easily replicated to other forms of oral cancer detection.

The proper regulation of RNA processing is critical for muscle development and the fine-tuning of contractile ability between muscle fiber-types. RNA binding proteins (RBPs) regulate the diverse steps in RNA processing including alternative splicing, which generates fiber-type specific isoforms of structural proteins that confer contractile sarcomeres with distinct biomechanical properties. Alternative splicing is disrupted in muscle diseases such as myotonic dystrophy and dilated cardiomyopathy, and is altered after intense exercise as well as with aging. It is therefore important to understand splicing and RBP function, but currently only a small fraction of the hundreds of annotated RBPs expressed in muscle have been characterized. Here we demonstrate the utility of Drosophila as a genetic model system to investigate basic developmental mechanisms of RBP function in myogenesis. We find that RBPs exhibit dynamic temporal and fiber-type specific expression patterns in mRNA-Seq data and display muscle-specific phenotypes. We performed knockdown with 105 RNAi hairpins targeting 35 RBPs and report associated lethality, flight, myofiber and sarcomere defects, including flight muscle phenotypes for Doa, Rm62, mub, mbl, sbr, and clu. Interestingly, knockdown phenotypes of spliceosome components, as highlighted by phenotypes for A-complex components SF1 and Hrb87F (hnRNPA1), revealed level- and temporal-dependent myofibril defects. We further show that splicing mediated by SF1 and Hrb87F is necessary for Z-disc stability and proper myofibril development, and strong knockdown of either gene results in impaired localization of Kettin to the Z-disc. Our results expand the number of RBPs with a described phenotype in muscle and underscore the diversity in myofibril and transcriptomic phenotypes associated with splicing defects. Drosophila is thus a useful model to gain disease-relevant insight into cellular and molecular phenotypes observed when expression levels of splicing factors, spliceosome components and splicing dynamics are altered.

المستخلص تصنيع لقاح مكون من الحمض النووي الريبوزي الرسول الخاص بالبروتينات المسئولة عن انتاج البروتينات نيورامنيديز والهيم اجليوتونين لفيروسي الانفلونزا الخنازير والطيورمحاط بجزيئات دهنية بحجم النانوميتر عدوى انفلونزا الخنازير وانفلونزا الطيور مشكلة خطيرة تؤرق العالم كله هذه الايام خصوصا انها مميتة لكثير من اطفال العالم . بعد فترة التعافي من الاصابة تتكون المناعة المكتسبة ضدها لمدة عام تقريبا. هذه الانفلونزا تسبب تسمم فيروسي في الدم بالاضافة للالتهاب الرئوي وهذامن بين اكبرالاسباب للوفاة بين الاطفال قبل سن عامين عالميا بشكل مباشر. الهدف من الدراسة هو انتاج لقاح الحمض النووي الريبوزي الرسول من نوع الام بالنانوتكنولوجي لبروتينات الهيم اجليوتونين والنيورامنيديز الموجودة على سطح هذه الفيروسات التي تساعدتها في الاتصاق بالعائل الذي ستتكاثر داخل خلاياه بالجهاز التنفسي. هذه الدراسة دراسة استكشافية ومن خلالها استطاعنا تصميم هذا اللقاح باستعمال نظام توصيل للقاح بالنانوتكنولوجي حجم جزيئاته 70نانوميمتر. اللقاح الجديد اظهر فاعلية بنسبة 60% واظهر فاعلية حيوية مقاربة واثار جانبية اقل بالمقارنة باللقاحات المتوفرة حاليا بالسوق الدوائي ضد هذا النوع من الفيروسات الوبائية. ABSTRACT Background: Worldwide, Swine and Avian influenza, or the H1N1 and H5N1 serotypes of the Influenza A virus, is a highly contagious illness. In recent years, the global incidence of mortality rate has surpassed 284,000 fatalities. Aim of the study: The production of mRNA vaccine lipid nanoparticles (LNP) to combat the deadly strains of Avian and Swine influenza (H1N1 and H5N1 of the influenza A serotype). Methodology: Polymerase chain reaction (PCR) was used to clone genes of interest encoding Haemagglutinin (HA) and Neuraminidase (NA) of Influenza A virus strains (H5N1 and H1N1) known as Avian flu and Swine flu, respectively. The genes were then inserted using the EcoR1, BAM Hind II restriction endonuclease type II, and Ligase enzyme into the pET-21(+) transcription vector plasmid. On the other hand, the hybrid transcription vectors were mixed with T7 RNA polymerase and ribonucleotides within a test tube after being linearized using EcoR II. Following their purification via reversed-phase high-performance liquid chromatography (RP-HPLC), the mRNAs of the HA and NA were encased in 70 nm LNPs and subjected to reverse-phase high-performance liquid chromatography (RP-HPLC). Lastly, immunogenicity studies were performed in stages 1/2 of randomized human and preclinical clinical trials. Results: The bivalent vaccination had around 63% efficacy in preclinical studies and approximately 60% efficacy in randomized human clinical trials. As shown by the ELISA test, strong neutralizing antibodies against HA were prevalent. Conclusion: The current study is a promising effort because of the development of the novel LNP-mRNA vaccine, which could lower the incidence of Avian and Swine flu infectious disorders.

Equine hepacivirus (EqHV, Flaviviridae, Hepacivirus) is a small, enveloped, RNA virus generally causing sub-clinical hepatitis with occasional fatalities. EqHV is reported in equids worldwide, but for Italy data are limited. To address this, a survey study was set up to estimate prevalence at national level and among different production categories (equestrian, competition, work and meat and reproduction) and national macro-regions (North, Central, South and Islands). Data obtained testing 1801 horse serum samples by Real-Time RT PCR were compared within the categories and regions. The NS3 fragment of the PCR-positive samples was sequenced by Sanger protocol for phylogenetic and mutational analysis. The tertiary structure of the NS3 protein was also assessed. The estimated national prevalence was 4.27% [1.97-6.59, 95%CI] and no statistical differences were detected among production categories and macro-regions. The phylogenesis confirmed the distribution in Italy of the three known EqHV subtypes, suggesting also a possible fourth sub-type that however requires further confirmation. Mutational profiles that could also affect the NS3 binding affinity to the viral RNA were detected. The present paper demonstrates that EqHV should be included in diagnostic protocols when investigating causes of hepatitis and in quality control protocols for blood derived products, due to its parental transmission.

The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of IDIF improves Alzheimer’s Disease (AD)-like pathology in mice, although mechanism of action and pharmacokinetics remain unknown. Radiolabeling IDIF with positron or gamma emitters may aid in the in vivo evaluation of IDIF using non-invasive nuclear imaging techniques. In this work, we report isotopic exchange reaction to obtain IDIF radiolabeled with 18F. [19F/ 18F]exchange reaction over IDIF in dimethylsulfoxide at 160 °C resulted in the formation of [18F]IDIF in 7±3% radiochemical yield in a 20 minutes reaction time, with a final radiochemical purity of >99%. Biodistribution studies after intravenous administration of [18F]IDIF in wild-type mice using positron emission tomography (PET) imaging showed capacity to cross the blood-brain barrier (ca. 1% of injected dose per gram of tissue in the brain at t&gt;10 min post administration), rapid accumulation in the liver, long circulation time and progressive elimination via urine. Our results open opportunities for future studies in larger animal species or human subjects.

Soybean seed sugars are among the most abundant beneficial compounds for human and animal consumption in soybean seeds. Higher seed sugars such as sucrose are desirable as it contributes to taste and flavor in soy-based food. Therefore, the objectives of this study were to use ‘Forrest’ by ‘Williams 82’ (F×W82) recombinant inbred line (RIL) soybean population (n=309) to identify quantitative trait loci (QTL) and candidate genes that control seed sugar (sucrose, stachyose, and raffinose) contents in two environments (North Carolina and Illinois) over two years (2018 and 2020). A total of 26 QTL that control seed sugars contents were identified and mapped on 16 soybean chromosomes (chrs.). Interestingly, five QTL regions were identified in both locations, Illinois and North Carolina, in this study on chrs. 2, 5, 13, 17, and 20. Amongst 57 candidate genes identified in this study, 16 were located within 10 Megabase (MB) of the identified QTL. Amongst them a cluster of four genes involved in the sugars’ pathway was collocated within 6 MB with two QTL that were detected in this study on chr. 17. Further functional validation of the identified genes could be beneficial in breeding programs to produce soybean lines with high beneficial sucrose and low raffinose family oligosaccharides.

A derivative series of 3,4-dimethoxy-β-nitrostyrene were synthesized and identified including new compound 6. The effect of antimicrobial activity of 3,4-alkyloxy modification of β-nitrostyrene was investigated. A molecular docking was also performed to obtain information about their interactions with Protein Tyrosine Phosphatase 1B (PTP1B). PTP1B containing cysteine 215 and arginine 221 as essential active residues plays a key role in signaling pathways that regulate various cell functions of microorganisms, which also act as negative regulator in signaling pathways of insulin that are involved in type 2 diabetes and other metabolic diseases. Compound 5 and 6 were the most potent as fragment of PTP1B inhibitor based on molecular docking, but compound 5 was more effective against Candida albicans. These compounds interact with serine 216 and arginine 221 residues. However, further research is needed to investigate their potential medicinal use.

Several herbivores feed on maize in field and storage setups making the development of multiple-insect resistance a critical breeding target. In this study, an association mapping panel of 341 tropical maize lines was evaluated in three field environments for resistance to FAW (fall armyworm) whilst bulked grains were subjected to MW (maize weevil) bioassay, genotyped with Diversity Array Technologies single nucleotide polymorphisms (SNPs) markers. A multi-locus genome-wide association study (GWAS) revealed 62 quantitative trait nucleotides (QTNs) associated with FAW and MW resistance traits on all 10 maize chromosomes, of which, 47 and 31 were discovered at stringent Bonferroni genome-wide significance level of 0.05 and 0.01, respectively, and located within or close to multiple-insect resistance genomic regions (MIRGRs) concerning FAW, SB, and MW. Sixteen QTNs influenced multiple-traits of which six were associated with resistance to both FAW and MW suggesting a pleiotropic genetic control. Functional prioritization of candidate genes (CGs) located within 10-30kb of the QTNs revealed 64 putative GWAS-based CGs (GbCGs) showing evidence of involvement in plant defense mechanisms. Only one GbCG was associated with each of five of the six combined-resistance QTNs, thus, reinforcing the pleiotropy hypothesis. In addition, through In-silico co-functional network inferences, an additional 107 Network-based CGs (NbCGs), biologically connected to the 64 GbCGs, differentially expressed under biotic or abiotic stress were revealed within MIRGRs. The provided multiple-insect resistance physical map should contribute to the development of combined-insect resistance in maize.

Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight in the etiopathogenesis of the disease. We systematically screened all studies that explored the association between polymorphisms and AD risks in cases of European and Asian ancestry and synthesized the available evidence through random-effects meta-analysis. We identified 97 studies that met our inclusion/exclusion criteria that examined 17 candidate loci in Europeans and 14 candidate genes in Asians. We confirmed the significant associations between FLG variants in both European and Asian populations and AD risk, while additional synthesis of available data revealed novel loci mapped to IL18 and TGFB1 genes in Europeans and IL12RB1 and MIF in Asians, that have not yet been identified by genome-wide association studies. Our findings provide comprehensive evidence for AD risk loci in cases of both European and Asian ancestries, validating previous associations as well as revealing novel loci that could imply previously unexplored biological pathways.

Vaccine refusal and hesitancy pose a critical challenge to public health, leading to delays in vaccination and compromising herd immunity. To address this issue, we conducted a comprehensive observational study on the adult Spanish population in 2021. Through an online questionnaire, we explored the sociodemographic and sociocultural factors, beliefs, and opinions of those refusing or holding hesitancy about vaccines, and their vaccination behaviours by vaccine type and sex. Our findings revealed that vaccine refusal rates were relatively low (16.8%), and mainly associated with influenza vaccination (10.3%). Greater refusal of vaccination was observed in over 60 years old, in those expressing hesitancy due to vaccine components and opposing free and compulsory vaccination, unaware that vaccination protects the community and being against consuming cow’s milk and the use of infant formulas for breastfeeding. Vaccine hesitancy was greatest in individuals under 31 years old, women, parents of children under 15 years old, against compulsory vaccination, unaware that vaccination protects the community, with hesitancy due to vaccine costs, and in favour of alternative and complementary treatments. These insights underscore the need for strategies to improve education about vaccination and dispel misconceptions are crucial for effectively reducing vaccine refusal and hesitancy across the population.

Hepatitis C virus (HCV) is a major medical health burden and leading cause of chronic liver disease and cancer worldwide. More than 58 million people are chronically infected with HCV, with 1.5 million new infections occurring each year. An effective HCV vaccine is a major public health and medical need as recognized by the World Health Organization. However, due to the high variability of the virus and its ability to escape the immune response, HCV rapidly accumulates mutations making a vaccine a formidable challenge. An effective vaccine must elicit broadly neutralizing antibodies (bnAbs) in a consistent fashion. After decades of studies from basic research through clinical development, the antigen of choice is considered to be the E1E2 envelope glycoprotein due to conserved, broadly neutralizing antigenic domains located in the constituent subunits of E1, E2, and the E1E2 heterodimeric complex itself. The challenge has been elicitation of robust humoral and cellular responses leading to broad virus neutralization due to the relatively low immunogenicity of this antigen. In view of this challenge, structure-based vaccine design approaches to stabilize key antigenic domains have been hampered due to the lack of E1E2 atomic-level resolution structures to guide them. Another challenge has been development of a delivery platform in which a multivalent form of the antigen can be presented in order to elicit a more robust anti-HCV immune response. Recent nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both the cellular and humoral components of the immune system. This review focuses on recent advances in understanding the E1E2 heterodimeric structure to facilitate a rational design approach and the potential for development of a multivalent nanoparticle-based HCV E1E2 vaccine. Both aspects are considered important in the development of an effective HCV vaccine that can effectively address viral diversity and escape.

Background: Acceleration of mass vaccination strategies is the only pathway to overcome the COVID-19 pandemic. Healthcare professionals and students have a key role in shaping public opinion about vaccines. This study aimed to evaluate the attitudes of dental students globally towards COVID-19 vaccines and explore the potential drivers for students' acceptance levels; Methods: A global cross-sectional study was carried out in February 2021 using an online ques-tionnaire. The study was liaised by the scientific committee of the International Association of Dental Students (IADS), and data was collected through the national and local coordinators of IADS member organizations. The dependent variable was the willingness to take the COVID-19 vaccine, and the independent variables included demographic characteristics, COVID-19-related experi-ence, and the drivers of COVID-19 vaccine-related attitude suggested by the WHO-SAGE; Results: A total of 6639 students from 22 countries representing all world regions responded to the ques-tionnaire properly. Their mean age was 22.06 ± 2.79 (17-40) years, and the majority were females (70.5%), in clinical years (66.8%), and from upper-middle-income economies (45.7%). In general, 22.5% of dental students worldwide were hesitant, and 13.9% rejected COVID-19 vaccines. The students in low- and lower-middle-income (LLMI) economies had significantly higher levels of vaccine hesitancy compared to their peers in upper-middle- and high-income (UMHI) economies (30.4% vs 19.8%; p < 0.001); Conclusions: The global acceptance level of dental students for COVID-19 vaccines was suboptimal, and their worrisome level of vaccine hesitancy was influenced by the socioeconomic context where the dental students live and study. The media and social media, public figures, insufficient knowledge about vaccines, and mistrust of governments and the pharmaceutical industry were barriers to vaccination. The findings of this study call for further implementation of epidemiology (infectious diseases) education within undergraduate dental curricula.

Introduction: Oral candidiasis is an opportunistic fungal infection, often caused by Candida albicans. One of the virulence factors of C. albicans is sterol 14a-demethylase or CYP51. Compounds of anthocyanins (ternatin, cyanin) and flavonoids (rutin, isoquercetin, kaempferol, myricetin, limocitrin) from the extract of the Clitoria ternatea (butterfly pea) plant are believed to have potential to inhibit the CYP51 virulence factor of C. albicans to suppress oral candidiasis. The purpose of this research was to investigate the interaction between the ligands of anthocyanins and flavonoids from C. ternatea (butterfly pea) with CYP51. Methods: The in silico study applied molecular docking to examine the molecular interactions (binding affinity) between the anthocyanin and flavonoid ligands of interest from C. ternatea and the CYP51 receptor of C. albicans. Results: Predicted interactions exist between the ligands of anthocyanins (ternatin, cyanin) and flavonoids (rutin, isoquercetin, kaempferol, myricetin, limocitrin) from C. ternatea and the CYP51 receptor of C. albicans. Conclusion: C. ternatea has the potential to provide anti-fungal agents that can inhibit or slow down the occurrence of oral candidiasis, as indicated by in silico studies. However, it is important to conduct additional research regarding the properties of the plant to determine the unknown aspects of its effects to the human body.