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Background: L. Australis is one of the most prevalent Leptospira strains infecting dogs, leading, in natural conditions, to severe life-threatening cases. Objective: The objective was to evaluate the onset and duration of immunity (OOI and DOI) induced by a new licensed quadrivalent antileptospiral vaccine (EURICAN® L4) including four Leptospira components (Canicola, Icterohaemorrhagiae, Grippotyphosa and Australis) against L. Australis. To this end, a severe L. Australis challenge model was developed, using a canine strain recently isolated from the field. Material and Methods: Seven- to ten-week-old puppies received two doses of the vaccine four weeks apart and were challenged with an L. Australis isolate two weeks (OOI) and 12 months (DOI) later. Mortality, clinical signs, leptospiremia, leptospiruria, renal carriage, and renal lesions were assessed after challenge. Results: The challenge induced multiple severe clinical signs in controls, leading to the death or euthanasia of 83% of puppies and 57% of adults. In controls, leptospiremia was detected in all dogs, leptospiruria in 67% of puppies and 86% of adults, kidneys tested positive for Leptospira in 83% of puppies and 71% of adults, and kidney lesions were observed in 100% of puppies and 86% of adults. In addition, thrombocytopenia associated with increased concentrations of urea, creatinine, and aspartate aminotransferase was recorded in controls displaying severe clinical signs. In both OOI and DOI studies, none of the vaccinates had clinical signs, no Leptospira was detected in blood, urine, and kidney samples, and no kidney lesions were observed in vaccinates. No significant changes in hematological and biochemical parameters in vaccinates were recorded. Conclusion: EURICAN® L4 was shown to induce quick and long-lasting protection against a severe L. Australis infectious challenge, preventing mortality, clinical signs, infection, bacterial excretion, renal lesions, and renal carriage.

Cancer remains a worldwide problem, and new treatment strategies are being actively developed. Peptides have the characteristics of good biocompatibility, strong targeting, functional diversity, modifiability, membrane permeable ability, and low immunogenicity, and they have been widely used to construct targeted drug delivery systems (DDSs). In addition, peptides, as endogenous substances, have a high affinity, which can not only regulate immune cells but also work synergistically with drugs to kill tumor cells, demonstrating significant potential for application. In this review, the latest progress of polypeptides-based nanocarriers in tumor therapy has been outlined, focusing on their applications in killing tumor cells and regulating immune cells. Additionally, peptides as carriers were found to primarily provide a transport function, which was also a subject of interest to us. At the end of the paper, the shortcomings in the construction of peptide nano-delivery system have been summarized, and possible solutions are proposed therein. The application of peptides provides a promising outlook for cancer treatment, and we hope this article can provide in-depth insights into possible future avenues of exploration.

(1) Background: In developed countries, public health faces a number of problems, including sedentary lifestyles and poor diets, which collectively contribute to the occurrence of preventable diseases. Noncommunicable diseases represent the leading cause of global mortality. Despite the promotion of healthy living, compliance remains a significant challenge. The integration of gamification into health apps has been demonstrated to facilitate behavioral change. Blockchain technology enhances the effectiveness of gamification by providing data trustability and support for auditable incentives. This feature is possible and easy due to the inherent characteristics of blockchain automating processes through Smart Contracts, rewarding participants and creating leaderboards in a transparent and reliable manner. The use of smart contracts and events enhances the traceability and reliability of decentralized applications, including healthcare. Interoperability in blockchain tools facilitates the deployment of complex environments. The aim of this research is the deployment of a tool for the implementation and testing of a gamification platform based on blockchain technology. (2) Methods: Pre-experimental research was carried out to assess the usability of the decentralized application developed. (3) Results: A decentralized application was developed with the objective of gamifying healthy habits. The application was evaluated using the System Usability Scale, obtaining a score of 80.49, and the Cronbach’s Alpha score, which was found to be 0.75. (4) Conclusions: A prototype of a decentralized application connected with a blockchain network to reward challenge fulfilment was deployed. Despite being in early development, it demonstrated high usability. Employing blockchain technology guarantees transparency and traceability while remaining in compliance with legal requirements like the General Data Protection Regulation.

Smart buildings play a key role in the complex ecosystem of cities and are often subject to barriers that limit their development. Although identifying these barriers is fundamental to creating an enabling environment for this segment’s expansion, few works aim to identify these challenges. This work has two main objectives: (1) to research the main barriers limiting the development of new smart building projects and (2) to prioritize these barriers from the perspective of professionals with experience in the field. We adopted an exploratory approach common in research that focuses on identifying and prioritizing variables related to a phenomenon, which is based on two main actions: obtaining information through a careful literature review and consulting professionals who work in the concerned field. The results showed that professionals assessed the 23 barriers identified through bibliographic research as important, with the most important being related to lack of qualified professionals, shortage of government policies, higher initial and construction costs, macroeconomic barriers and access to financing, high cost of intelligent systems and technologies, regulatory barriers, lack of knowledge about the current and potential benefits of smart buildings, and more complex design and construction.

Integrated ocean management (IOM) aligns with the United Nations’ Sustainable Development Goals (SDGs) and serves as a crucial strategy for promoting the enduring health of marine ecosystems and the sustainable utilization of marine resources. An analysis of the evolution of China’s integrated ocean management policy (IOMP) is crucial for providing valuable guidance in achieving sustainable growth in marine management and the marine economy for both China and other coastal nations worldwide. This paper studies the evolution characteristics, challenges, and prospects of IOMP in China since 1978 using content analysis. The findings indicate that the evolution of IOMP can be categorized into four stages: the germination period (1978–1998), the construction period (1999–2009), the systematization period (2010–2017), and the strategization period (2018–present), based on the state of international marine management. The IOMP has transitioned over time from its initial emphasis on resource development during the germination period to a strategization period that prioritizes the full development of all parts of the system. However, the ultimate goal has consistently been to achieve harmonious coexistence between people and the sea. China’s IOMP has experienced a progressive development; nevertheless, it continues to encounter obstacles such as the pressing requirement to revise sea-related policies and the absence of policy alignment. The objective of this paper is to explore the evolution, challenges, and prospects of China’s IOMP to better improve the land–sea coordination policy, strengthen international judicial cooperation. and provide effective policy reference for other maritime countries.

A large body of evidence highlights the importance of psycho-behavioural skills as a key feature of talent development in sport. The purpose of this study was to explore pedagogic intentions of coaches in the psychological development of athletes. Eleven coaches were purposefully sampled for interview based on a track record of expert practice. Using reflexive thematic analysis, three overarching themes were generated as representing the coaches’ work: knowing and shaping the athlete’s needs, purposeful breadth and flexibility of teaching approaches, using challenge to test skill development, and the necessity of review and refinement. Reflecting these data, we suggest the need for an increased appreciation of the role of the sports coach beyond the technical and tactical, with the recommendation that coaches build their knowledge and skillset across a breadth of domains to support the psychological development of athletes more effectively.

The construction industry accounts for approximately one-third of the total waste generation globally. With the United Nations projecting a population increase of 2 billion within the next three decades, there is a heightened demand for building stock, generating unprecedented volumes of construction and demolition waste (CDW). To combat this, circular economy strategies are purported to help alleviate the prevailing situation. But a number of challenges are jeopardizing their implementation in the construction industry and preventing from achieving the UN Sustainable Development Goals, net zero carbon and zero avoidable waste targets. This paper systematically analyzes 54 research articles, published in the past decade within major peer-reviewed English-language scholarly publications in the form of a systematic research review. In doing so, it aims to identify and classify the challenges that prevent improved CDW management by assimilating previous research results in support of a circular economy. The classification and analysis using a PESTLE model offers insights into gaps and differences between categories, as well as regions and countries. This initial step could contribute to a better understanding of these barriers, along with associated solutions, which could result in a significant reduction on the impact of construction activities, therefore facilitating the development of an effective circular economy in the sector.

Bacteriophages, which are viruses with restricted tropism for bacteria, have been employed for over a century as antimicrobial agents; they have been largely abandoned in Western countries but are constantly used in Eastern European countries with the advent of antibiotics. In recent decades, the growing spread of multidrug-resistant bacteria, which pose a serious threat to worldwide public health, imposed an urgent demand for alternative therapeutic approaches to antibiotics in animal and human fields. Based on this requirement, numerous studies have been published on developing and testing bacteriophage-based therapy. Overall, the literature largely supports the potential of this perspective but also highlights the need for additional research as the current standards are inadequate to receive approval from regulatory authorities. This review aims to update and critically revise the current knowledge on the application of bacteriophages to treat bacterial-derived infectious diseases in animals in order to provide topical perspectives and innovative advances.

Wound care professionals provide proper diagnosis and treatment with heavy reliance on images and image documentation. Segmentation of wound boundaries in images is a key component of the care and diagnosis protocol since it is important to estimate the area of the wound and provide quantitative measurement for the treatment. Unfortunately, this process is very time-consuming and requires a high level of expertise, hence the need for automatic wound measurement methods. Recently, automatic wound segmentation methods based on deep learning have shown promising performance; yet, they heavily rely on large training datasets. A few wound image datasets were published including the Diabetic Foot Ulcer Challenge dataset, the Medetec wound dataset, and WoundDB. Existing public wound image datasets suffer from small size and a lack of annotation. There is a need to build a fully annotated dataset to benchmark wound segmentation methods. To address these issues, we propose the Foot Ulcer Segmentation Challenge (FUSeg), organized in conjunction with the 2021 International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI). It contains 1210 pixel-wise annotated foot ulcer images collected over 2 years from 889 patients. The submitted algorithms are reviewed in this paper and the dataset can be accessed through the Foot Ulcer Segmentation Challenge website.

Vaccination against the Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is widely practiced in both sows and piglets. However, it has been shown that multivaccinated sows sometimes lack a detectable antibody response, testing seronegative in ELISA (non-responders). Moreover, PRRSV-vaccinated piglets can remain seronegative as well, which is mainly attributed to the interference of maternally derived antibodies (MDAs). The current study investigated the impact of the sow’s immune status on the PRRSV vaccine effectiveness in the progeny. The experimental trial included forty-eight piglets (n = 48) originating from a commercial Belgian breeding herd, with twenty-four piglets born from PRRSV vaccinated responder sows (E+ piglets) and twenty-four piglets born from PRRSV vaccinated non-responder sows (E− piglets). Eight piglets in each group were either non-vaccinated (NoVac piglets; n = 8), intramuscularly vaccinated (IM piglets; n = 8), or intradermally vaccinated (ID piglets; n = 8), with the same PRRSV-1 vaccine as used in the sow population. Vaccination was performed at weaning at three weeks of age, and all study piglets were challenged with a high dose of the PRRSV-1 07V063 strain at 6 weeks of age. A clear interference of MDAs was observed in the E+ piglets: 66.7% of the vaccinated E+ piglets lacked an antibody response at 3 weeks post-vaccination (non-responders). Consequently, post-challenge, only the responding E+ piglets had a significantly reduced serum viremia compared to the E+ NoVac piglets. The observed viremia in the non-responding E+ piglets was similar to the viremia of the E+ NoVac piglets. In the vaccinated E− piglets, a lack of antibody response at 3 weeks post-vaccination was observed in 18.8% of the piglets. Interestingly, despite the lack of a vaccine antibody response, the non-responding E− piglets had a significantly reduced serum viremia compared to the NoVac E− piglets. In contrast, the viremia of the responding E− piglets was only numerically reduced compared to the NoVac E− piglets. Finally, some clear differences were observed in both the kinetics of infection and the immune responses post-challenge between the E+ and E− piglets. The results of this study confirm the consequences of the MDA interference on the induced partial protection of PRRSV vaccination in experimentally challenged piglets. More research is warranted to understand the immunological mechanisms behind MDA interference in PRRSV vaccination and to explain the observed differences between E+ and E− piglets.

Drug discovery plays a critical role in advancing human health by developing new medications and treatments to combat diseases. How to accelerate the pace and reduce the costs of new drug discovery has long been a key concern for the pharmaceutical industry. Fortunately, by leveraging advanced algorithms, computational power and biological big data, artificial intelligence (AI) technology, especially machine learning (ML), holds the promise of making the hunt for new drugs more efficient. Recently, the Transformer-based models that have achieved revolutionary breakthroughs in natural language processing have sparked a new era of their applications in drug discovery. Herein, we introduce the latest applications of ML in drug discovery, highlight the potential of advanced Transformer-based ML models, and discuss the future prospects and challenges in the field.

Different virulence variants of A. pleuropneumoniae are involved in the etiology of porcine pleuropneumonia. The purpose of the present trial was examination of the virulence of the Actinobacillus pleuropneumoniae A-85/14 strain, the type strain of serovar 16, in an animal challenge experiment. Thirty 12-week-old piglets seronegative for A. pleuropneumoniae were allocated into three trial groups each of 10 animals, and they were infected intranasally with 106, 107, or 108 colony forming units (cfu) of the strain, respectively. Clinical signs were recorded twice a day, and the animals were euthanized 6 days after the infection. Typical clinical signs and postmortem lesions of porcine pleuropneumonia were seen in the animals of each trial group; however, they were generally mild, and no significant differences could be seen between the three groups. Even 106 colony forming units of A. pleuropneumoniae A-85/14 strain could induce clinical signs and lesions. Based on these results, the type strain of serovar 16 of A. pleuropneumoniae must be regarded as a typical pathogenic strain of the species.

Intervention parameters such as the challenge, amount, and dosage (challenge × amount) have the potential to alter the efficacy of rehabilitation interventions after stroke. This systematic review investigated the effect of intervention parameters of challenge, amount, and dosage on improvements in walking outcomes following treadmill training (TT) and comparison interventions in people with stroke. Randomized controlled trials were included if they: (i) investigated interventions of TT or bodyweight-supported TT (BWSTT); (ii) made comparisons with other physiotherapy interventions, other types of TT, or no intervention; (iii) studied people with stroke; (iv) reported sufficient data on challenge and amount parameters; and (v) measured walking speed or endurance. Completeness of reporting was evaluated using the TIDieR-Rehab checklist and risk of bias was assessed using the revised Cochrane risk-of-bias tool. The review included 26 studies; 15 studies compared TT or BWSTT with other physiotherapy interventions and 11 studies compared different types of TT. Meta-analyses provided evidence with low to moderate certainty that greater differences in challenge and dosage between treadmill and comparison physiotherapy interventions produced greater effects on walking endurance (p < 0.01). However, challenge and dosage did not influence walking speed outcomes. The analysis of intervention amount was limited by the lack of studies that manipulated the amount of intervention. Overall, the findings indicate that, after stroke, some of the efficacy of TT on walking endurance can be explained by the challenge level during training. This supports the implementation of TT at higher challenge levels in stroke rehabilitation practice.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) remains an infectious agent with high importance in the swine industry. In this study, the influence of maternally derived antibodies (MDAs) on an experimental PRRSV-1 challenge is investigated. Piglets included in the study (n = 36) originated from a Belgian farrow-to-finish herd in which the sow population was routinely vaccinated with a modified live vaccine against PRRSV. Eighteen piglets were born from three PRRSV-seropositive sows (responders to vaccination) and had a clear presence of PRRSV-specific MDAs (E+ piglets). The other eighteen piglets were born from three PRRSV-seronegative sows (non-responders to vaccination) and did not have PRRSV-specific MDAs (E− piglets). In each group, twelve piglets were intranasally challenged with a high dose of the heterologous PRRSV-1 07V063 strain, the remaining piglets were mock-challenged (PBS) and served as controls. During the first days after infection, higher serum viremia and nasal shedding were observed in the challenged E− piglets compared to the challenged E+ piglets. However, at 10 days post-infection, the peak serum viremia was significantly higher in the E+ piglets in comparison to the E− piglets and serum viremia remained slightly higher in this group until the end of the study. Additionally, the two challenged groups had a different immune response to the PRRSV infection. The E− challenged piglets showed an earlier and more intense seroconversion, leading to significantly higher antibody titers at 10 dpi compared to the E+ challenged piglets. Furthermore, a trend towards both higher induction of serum IFN-γ and higher induction of IFN-γ secreting cells was observed in the E− challenged piglets. In contrast, a significantly higher induction of serum TNF-α at 7 dpi was seen in the E+ challenged piglets compared to the E− challenged piglets. The results gathered in this study suggest that PRRSV-specific MDAs induce partial protection during the early stages of infection but are not sufficient to protect against a high challenge dose. The presence of piglets lacking PRRSV-specific MDAs might pose a risk for PRRSV infection and enhanced transmission in pig farms in young piglets.

Early studies on the COVID-19 pandemic suggest that the working from home (WFH) mandate and unusual caregiving arrangements have dramatically impacted the employment of women, especially those with young children. This study explores women’s perceptions of the WFH mandate arrangement. Data were collected from the female workforce in the Australian construction industry using an online questionnaire. The specific objectives were to (i) explore their WFH experiences; (ii) examine their perceived impacts of WFH challenges on work activities and performance; and (iii) explore the relationships among critical challenges, the respondents’ demographic characteristics and their overall satisfaction with WFH and preference for WFH after COVID. Although most respondents were new to the WFH arrangement, there is evidence suggesting that they were adapting well to the sudden shift to a WFH arrangement. Sixteen (out of twenty-two) challenges recorded positive perceived impacts on work activities and performance. The top three critical challenges were (i) mutual trust between you and your work supervisor; (ii) availability of suitable space at home; and (iii) information and communication exchanges via virtual meetings. The respondents also indicated positive satisfaction with a WFH arrangement along with perceived positive work performance while WFH. Most of them indicated high preference for WFH after COVID, which was positively correlated with the level of education attainment. The critical challenges identified together with a set of negative factors might be useful for employment organizations to re-optimize their WFH practices.

Metritis is a postpartum uterine disease with greater incidence in primiparous than in multiparous cows. In primiparous cows, the impact on production and health is lessened, presumably due to a superior immune response. Here, we tested whether an in vivo model of clinical metritis induction developed for postpartum multiparous Holstein cows would produce similar results in primiparous cows. Thirty-six cows were randomly assigned to one of three groups and received intrauterine infusion within 24 h of parturition. The controls were infused with sterile saline; the low-dose group received a bacterial cocktail containing 103 cfu of Escherichia coli, Trueperella pyogenes, and Fusobacterium necrophorum; and the high-dose group were infused with 106 cfu of the same cocktail. Production, health traits, and the vaginal discharge culture were assessed daily, from enrollment until 14 d in milk. Clinical metritis occurred in 64% of high-dose cows, 33% of the controls, and 42% of low-dose cows, with no significant difference of incidence between groups. However, when accounting by time, high-dose cows had a 2.7 times greater hazard of metritis compared with the controls. The bacterial challenge affected milk production and dry matter intake tended to decrease. In the high-dose group, a greater growth of F. necrophorum in the selective medium was also observed, suggesting an association with metritis. Therefore, this study suggests intrauterine inoculation with 106 cfu of this bacterial cocktail elicits physical and clinical outcomes consistent with clinical metritis.

Background: L. Australis is one of the most prevalent Leptospira strains infecting dogs, leading, in natural conditions, to severe life-threatening cases., Objective: The objective was to evaluate the onset and duration of immunity (OOI and DOI) induced by a new licensed quadrivalent antileptospiral vaccine (EURICAN ® L4) including four Leptospira components (Canicola, Icterohaemorrhagiae, Grippotyphosa and Australis) against L. Australis. To this end, a severe L. Australis challenge model was developed, using a canine strain recently isolated from the field., Material and Methods: Seven- to ten-week-old puppies received two doses of the vaccine four weeks apart and were challenged with an L. Australis isolate two weeks (OOI) and 12 months (DOI) later. Mortality, clinical signs, leptospiremia, leptospiruria, renal carriage, and renal lesions were assessed after challenge., Results: The challenge induced multiple severe clinical signs in controls, leading to the death or euthanasia of 83% of puppies and 57% of adults. In controls, leptospiremia was detected in all dogs, leptospiruria in 67% of puppies and 86% of adults, kidneys tested positive for Leptospira in 83% of puppies and 71% of adults, and kidney lesions were observed in 100% of puppies and 86% of adults. In addition, thrombocytopenia associated with increased concentrations of urea, creatinine, and aspartate aminotransferase was recorded in controls displaying severe clinical signs. In both OOI and DOI studies, none of the vaccinates had clinical signs, no Leptospira was detected in blood, urine, and kidney samples, and no kidney lesions were observed in vaccinates. No significant changes in hematological and biochemical parameters in vaccinates were recorded., Conclusion: EURICAN ® L4 was shown to induce quick and long-lasting protection against a severe L. Australis infectious challenge, preventing mortality, clinical signs, infection, bacterial excretion, renal lesions, and renal carriage.

Background: The COVID-19 pandemic has worsened sedentary lifestyles and unhealthy eating habits. It is crucial to promote proper training and healthy habits for all to prevent physical and cognitive decline. This should be a priority in health and education initiatives to reduce deaths and noncommunicable diseases. Guidelines for nutrition, physical activity, and sleep emphasize the importance of healthy habits. The goal is to develop a recommendation tool with a diverse range of challenges to positively impact users’ health. Methods: The process involves thoroughly obtaining precise user profiles through widely used questionnaires such as the Short-Form Health survey, the short Healthy Eating Index, and the Oviedo Sleep Questionnaire, and characterizing the challenges. Then, an algorithm will be developed to identify and prioritize the most suitable challenges for each user, ensuring personalized recommendations. Results: A pool of 30 health challenges was created based on reputable recommendations and experts. The system underwent validation by external experts and received positive user feedback, confirming its effectiveness. The panel of experts and users validated the personalized and reliable recommendations. Conclusions: Simple lifestyle interventions have shown promise for primary prevention in developed countries. A prototype system has been created to evaluate the individual weakness of users and suggest evidence-based lifestyle challenges. The system conducts a thorough health assessment and ensures feasibility for preventive purposes. Validation has proven the system’s effectiveness in recommending health-enhancing challenges with no adverse effects. The design of the model supports the seamless addition of new challenges by eventual third parties, ensuring interoperability and scalability.

Skin diseases are among the most prevalent non-fatal conditions worldwide. The transdermal drug delivery system (TDDS) has emerged as a promising approach for treating skin diseases, owing to its numerous advantages such as high bioavailability, low systemic toxicity, and improved patient compliance. However, the effectiveness of the TDDS is hindered by several factors, including the barrier properties of the stratum corneum, the nature of the drug and carrier, and delivery conditions. In this paper, we provide an overview of the development of the TDDS from first-generation to fourth-generation systems, highlighting the characteristics of each carrier in terms of mechanism composition, penetration method, mechanism of action, and recent preclinical studies. We further investigated the significant challenges encountered in the development of the TDDS and the crucial significance of clinical trials.

Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through exposure of infected pigs, ingestion of contaminated food, or through contact with an infected person. With no approved treatments or vaccines, NiV poses a threat to human public health and has epidemic potential. To aid with the assessment of emerging interventions being developed, an expansion of preclinical testing capability is required. Given variations in the model parameters observed in different sites during establishment, optimisation of challenge routes and doses is required. Upon evaluating the hamster model, an intranasal route of challenge was compared with intraperitoneal delivery, demonstrating a more rapid dissemination to wider tissues in the latter. A dose effect was observed between those causing respiratory illness and those resulting in neurological disease. The data demonstrate the successful establishment of the hamster model of NiV disease for subsequent use in the evaluation of vaccines and antivirals.

Digital transformation of higher education institutions (HEIs) is of paramount importance in today’s technology-driven world. However, there are numerous barriers that hinder the successful implementation of digital transformation initiatives in HEIs. In this article, we identify and classify these barriers based on a systematic literature review. The findings reveal twenty distinct barriers that inhibit digital transformation in higher education. These were then organised into six broad categories, namely environmental, strategic, organisational, technological, people-related and cultural. The study provides a comprehensive understanding of the barriers faced, facilitating the development of effective strategies and interventions. Our analysis provides valuable information for higher education institutions, policy makers and stakeholders involved in digital transformation initiatives.

The SARS-CoV-2 pandemic demonstrated the need for potent and broad-spectrum vaccines. This study reports the development and testing of a lumpy skin disease virus (LSDV)-vectored vaccine against SARS-CoV-2, utilizing stabilized spike and conserved nucleocapsid proteins as antigens to develop robust immunogenicity. Construction of the vaccine (LSDV-SARS2-S,N) was confirmed by polymerase chain reaction (PCR) amplification and sequencing. In vitro characterization confirmed that cells infected with LSDV-SARS2-S,N expressed SARS-CoV-2 spike and nucleocapsid protein. In BALB/c mice, the vaccine elicited high magnitude IFN-γ ELISpot responses (spike: 2808 SFU/106 splenocytes) and neutralizing antibodies (ID50 = 6552). Testing in hamsters, which emulate human COVID-19 disease progression, showed the development of high titers of neutralizing antibodies against the Wuhan and Delta SARS-CoV-2 variants (Wuhan ID50 = 2905; Delta ID50 = 4648). Additionally, hamsters vaccinated with LSDV-SARS2-S,N displayed significantly less weight loss, lung damage, and reduced viral RNA copies following SARS-CoV-2 infection with the Delta variant as compared to controls, demonstrating protection against disease. These data demonstrate that LSDV-vectored vaccines display promise as an effective SARS-CoV-2 vaccine and as a potential vaccine platform for communicable diseases in humans and animals. Further efficacy testing and immune response analysis, particularly in non-human primates, are warranted.

Positive energy districts (PEDs) are urban areas which seek to take an integral approach to climate neutrality by including technological, spatial, regulatory, financial, legal, social, and economic perspectives. It is still a new concept and approach for many stakeholders. ChatGPT, a generative pre-trained transformer, is an advanced artificial intelligence (AI) chatbot based on a complex network structure and trained by the company OpenAI. It has the potential for the fast learning of PED. This paper reports a trial test in which ChatGPT is used to provide written formulations of PEDs within three frameworks: challenge, impact, and communication and dissemination. The results are compared with the formulations derived from over 80 PED experts who took part in a two-day workshop discussing many aspects of PED research and development. The proposed methodology involves querying ChatGPT with specific questions and recording its responses. Subsequently, expert opinions on the same questions are provided to ChatGPT, aiming to elicit a comparison between the two sources of information. This approach enables an evaluation of ChatGPT’s answers in relation to the insights shared by domain experts. By juxtaposing the outputs, a comprehensive assessment can be made regarding the reliability, accuracy, and alignment of ChatGPT’s responses with expert viewpoints. It is found that ChatGPT can be a useful tool for the rapid formulation of basic information about PEDs that could be used for its wider dissemination amongst the general public. The model is also noted as having a number of limitations, such as providing pre-set single answers, a sensitivity to the phrasing of questions, a tendency to repeat non-important (or general) information, and an inability to assess inputs negatively or provide diverse answers to context-based questions. Its answers were not always based on up-to-date information. Other limitations and some of the ethical–social issues related to the use of ChatGPT are also discussed. This study not only validated the possibility of using ChatGPT to rapid study PEDs but also trained ChatGPT by feeding back the experts’ discussion into the tool. It is recommended that ChatGPT can be involved in real-time PED meetings or workshops so that it can be trained both iteratively and dynamically.

The concept of intermediate care is gaining increasing recognition in Italy as a critical strategy for improving quality of care and promoting the integration of healthcare services across different settings. This is driven by demographic changes and the growing prevalence of chronic conditions. One of the key challenges in delivering intermediate care in Italy is ensuring that care is person-tailored, which requires a shift towards a more holistic approach that prioritizes individual preferences and values. This requires greater collaboration and communication across different healthcare settings and a coordinated approach to the delivery of care that promotes innovation and the use of technology to support remote monitoring and care delivery. Despite these challenges, intermediate care offers significant opportunities with which to enhance the quality of care, reduce healthcare costs, and promote social cohesion as well as community engagement. Overall, a coordinated and comprehensive approach is required to address the challenges and opportunities associated with intermediate care and to deliver person-tailored care that improves health outcomes as well as sustainability in Italy.

The objective of this study was to evaluate the potential benefits of feeding spray-dried porcine plasma (SDPP) to pigs infected with African swine fever virus (ASFV). Two groups of twelve weaned pigs each were fed with CONVENTIONAL or 8% SDPP enriched diets. Two pigs (trojans)/group) were injected intramuscularly with the pandemic ASFV (Georgia 2007/01) and comingled with the rest of the pigs (1:5 trojan:naïve ratio) to simulate a natural route of transmission. Trojans developed ASF and died within the first week after inoculation, but contact pigs did not develop ASF, viremia, or seroconversion. Therefore, three more trojans per group were introduced to optimize the ASFV transmission (1:2 trojan:naïve ratio). Blood, nasal, and rectal swabs were weekly harvested, and at end of the study ASFV-target organs collected. After the second exposure, rectal temperature of conventionally fed contact pigs increased >40.5 °C while fever was delayed in the SDPP contact pigs. Additionally, PCR Ct values in blood, secretions, and tissue samples were significantly lower (p < 0.05) for CONVENTIONAL compared to SDPP contact pigs. Under these study conditions, contact exposed pigs fed SDPP had delayed ASFV transmission and reduced virus load, likely by enhanced specific T-cell priming after the first ASFV-exposure.

This study aimed to evaluate the effects of feeding spray-dried porcine plasma (SDPP) on the protection afforded by the BA71∆CD2 African swine fever virus (ASFV) vaccine prototype. Two groups of pigs acclimated to diets without or with 8% SDPP were intranasally inoculated with 105 plaque-forming units (PFU) of live attenuated ASFV strain BA71∆CD2 and, three weeks later, left in direct contact with pigs infected with the pandemic Georgia 2007/01 ASFV strain. During the post-exposure (pe) period, 2/6 from the conventional diet group showed a transient peak rectal temperature >40.5 °C before day 20 pe, and some tissue samples collected at 20 d pe from 5/6 were PCR+ for ASFV, albeit showing Ct values much higher than Trojan pigs. Interestingly, the SDPP group did not show fever, neither PCR+ in blood nor rectal swab at any time pe, and none of the postmortem collected tissue samples were PCR+ for ASFV. Differential serum cytokine profiles among groups at vaccination, and a higher number of ASFV-specific IFNϒ-secreting T cells in pigs fed with SDPP soon after the Georgia 2007/01 encounter, confirmed the relevance of Th1-like responses in ASF protection. We believe that our result shows that nutritional interventions might contribute to improving future ASF vaccination strategies.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of several variants of concern (VOC) with increased immune evasion and transmissibility. This has motivated studies to assess protection conferred by earlier strains following infection or vaccination to each new VOC. We hypothesized that while NAbs play a major role in protection against infection and disease, a heterologous reinfection or challenge may gain a foothold in the upper respiratory tract (URT) and result in a self-limited viral infection accompanied by an inflammatory response. To test this hypothesis, we infected K18-hACE2 mice with SARS-CoV-2 USA-WA1/2020 (WA1) and, after 24 days, challenged with WA1, Alpha, or Delta. While NAb titers against each virus were similar across all cohorts prior to challenge, the mice challenged with Alpha and Delta showed weight loss and upregulation of proinflammatory cytokines in the URT and lower RT (LRT). Mice challenged with WA1 showed complete protection. We noted increased levels of viral RNA transcripts only in the URT of mice challenged with Alpha and Delta. In conclusion, our results suggested self-limiting breakthrough infections of Alpha or Delta in the URT, which correlated with clinical signs and a significant inflammatory response in mice.

Edwardsiella ictaluri and Flavobacterium covae are pervasive bacterial pathogens associated with significant losses in catfish aquaculture. Bacterial coinfections have the potential to increase outbreak severity and can worsen on-farm mortality. A preliminary assessment of in vivo bacterial coinfection with E. ictaluri (S97-773) and F. covae (ALG-00-530) was conducted using juvenile channel catfish (Ictalurus punctatus). Catfish were divided into five treatment groups: (1) mock control; (2) E. ictaluri full dose (immersion; 5.4 × 105 CFU mL−1); (3) F. covae full dose (immersion; 3.6 × 106 CFU mL−1); (4) E. ictaluri half dose (immersion; 2.7 × 105 CFU mL−1) followed by half dose F. covae (immersion; 1.8 × 106 CFU mL−1); and (5) F. covae half dose followed by half dose E. ictaluri. In the coinfection challenges, the second inoculum was delivered 48 h after the initial exposure. At 21 days post-challenge (DPC), the single dose E. ictaluri infection yielded a cumulative percent mortality (CPM) of 90.0 ± 4.1%, compared with 13.3 ± 5.9% in the F. covae group. Mortality patterns in coinfection challenges mimicked the single dose E. ictaluri challenge, with CPM of 93.3 ± 5.4% for fish initially challenged with E. ictaluri followed by F. covae, and 93.3 ± 2.7% for fish exposed to F. covae and subsequently challenged with E. ictaluri. Despite similarities in the final CPM within the coinfection groups, the onset of peak mortality was delayed in fish exposed to F. covae first but was congruent with mortality trends in the E. ictaluri challenge. Catfish exposed to E. ictaluri in both the single and coinfected treatments displayed increased serum lysozyme activity at 4-DPC (p < 0.001). Three pro-inflammatory cytokines (il8, tnfα, il1β) were evaluated for gene expression, revealing an increase in expression at 7-DPC in all E. ictaluri exposed treatments (p < 0.05). These data enhance our understanding of the dynamics of E. ictaluri and F. covae coinfections in US farm-raised catfish.

Background: In South Africa, children with cerebral palsy are nested within a family setting by immediate relatives, particularly in the rural areas. These immediate relatives are regarded as caregivers and are not trained with regard to providing care to children with special needs. Therefore, they have to find ways to adapt to their new roles of caregiving using the available resources. The aim of this paper is to present the challenges encountered by caregivers of children with cerebral palsy in rural areas of South Africa. Methods: This qualitative, explorative, descriptive, and contextual study included 10 caregivers for children with cerebral palsy who were purposively recruited from the three respective hospitals in Vhembe District within Limpopo Province. Data were collected through individual in-depth interviews and analysed using a thematic approach. Ethical considerations and measures to ensure trustworthiness were upheld throughout the study. Results: Four themes emerged from the study, namely economic problems facing caregivers; health problems encountered by caregivers; maltreatment of caregivers by community members, as well as access to transport for caregivers and children. Conclusion: Participants narrated that caring for a child with cerebral palsy is not an easy task for the caregiver, particularly in the rural areas of South Africa. They encounter various challenges as they strive to provide quality care to the children that they are caring for. An investigation is recommended concerning the kind of model which should be developed to support caregivers in caring for children with cerebral palsy in the rural areas.

In the past decade, the numerical modelling of braided river morphodynamics has experienced a significant advance due to the increasing computer power and the development of numerical techniques. Numerical models are quite efficient in exploring scenarios with different settings, and they can be applied to investigate the complicated physics laws of natural braided rivers and manage complex river engineering problems. However, braided river models are far from fully developed, e.g., the representation of flow and sediment transport, model sensitivity, essential effects of sediment transport, bank erosion and vegetation, and require intensive refinement and validation to enhance their prediction accuracy. The recent application of advanced field measurement techniques offers model development a new chance by providing abundant measurement data of a high quality. The present study reviews the essential mechanisms and applications of typical braided river models; compares their accuracy; discusses the recent progress, advantages and shortcomings; and illustrates the challenges and future research trends.

(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity and efficacy of the third-generation oral rabies virus vaccine strain, SPBN GASGAS, in domestic dogs, dogs were offered an egg-flavoured bait containing 3.0 mL of the vaccine (107.5 FFU/mL) or a placebo egg-flavoured bait. Subsequently, these 25 vaccinated and 10 control animals were challenged approximately 6 months later with a dog rabies virus isolate. Blood samples were collected at different time points postvaccination and examined by ELISA and RFFIT. (3) Results: All but 1 of the 25 vaccinated dogs survived the challenge infection; meanwhile, all 10 control dogs succumbed to rabies. The serology results showed that all 25 vaccinated dogs seroconverted in ELISA (>40% PB); meanwhile, only 13 of the 25 vaccinated dogs tested seropositive ≥ 0.5 IU/mL) in RFFIT. (4) Conclusions: The SPBN GASGAS rabies virus vaccine meets the efficacy requirements for live oral rabies vaccines as laid down by the European Pharmacopoeia and the WOAH Terrestrial Manual. SPBN GASGAS already fulfilled the safety requirements for oral rabies vaccines targeted at dogs. Hence, the egg-flavoured bait containing SPBN GASGAS is the first oral vaccine bait that complies with WOAH recommendations for the intended use of oral vaccination of free-roaming dogs against rabies.

The objective of this study was to evaluate the efficacy of two multivalent commercial porcine circovirus (PCV) vaccines against heterologous PCV2d challenges. A total of 24 crossbred male pigs aged 26 days selected from a specific pathogen-free herd were randomly divided into four groups (six pigs per group) and assigned as follows: negative control (unvaccinated/sham-challenge), vaccinated with chimeric PCV1-2a vaccine (PCV1-2a/PCV2d-challenge), vaccinated with chimeric PCV1-2a-2b vaccine (PCV1-2a-2b/PCV2d-challenge) and positive control (unvaccinated/PCV2d-challenge). At 21 days after vaccination, the pigs were intranasally and intramuscularly inoculated with either sham or field isolates of PCV2d (PCV2d/149/TH/2020). After being challenged, blood samples were obtained weekly and analyzed for levels of PCV2d viremia, neutralizing antibodies, and IgG against PCV2. At 30 days post-challenge (DPC), the pigs were euthanized and then subjected to pathological evaluations and molecular analysis. The results indicated that pigs in the PCV1-2a-2b/PCV2d-challenge and the PCV1-2a/PCV2d-challenge groups possessed significantly greater levels of PCV2d-neutralizing antibody titer when compared with the positive control group. Moreover, pigs in the PCV1-2a-2b/PCV2d-challenge group exhibited a lower degree of severity in terms of gross lesion scores and lower levels of PCV2 viremia when compared with the positive control group. This study demonstrated that vaccinating pigs with either the PCV1-2a or PCV1-2a-2b chimeric vaccines elicits a potent immune response against PCV2d infection and reduces viremia after PCV2d inoculation in pigs.

With economic development, environmental problems are becoming more and more prominent, and achieving green chemistry is an urgent task nowadays, which creates an opportunity for the development of supercritical foaming technology. The foaming agents used in supercritical foaming technology are usually supercritical carbon dioxide (ScCO2) and supercritical nitrogen (ScN2), both of which are used without environmental burden. This technology can reduce the environmental impact of polymer foam production. Although supercritical foaming technology is already in production in some fields, it has not been applied on a large scale. Here, we present a detailed analysis of the types of foaming agents currently used in supercritical foaming technology and their applications in various fields, summarizing the technological improvements that have been made to the technology. However, we have found that today’s supercritical technologies still need to address some additional challenges to achieve large-scale production.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection pre-clinically and in humans. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses, which are delivered by replication-deficient vector ChAdOx1. It directs T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8 + T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the β-coronavirus family.

Urban drainage systems play an important role in the complex ecosystem of cities and are often subject to challenges that hinder their functioning. Although identifying these challenges is essential for developing policies and actions to improve drainage systems, there is a lack of studies addressing these challenges. This work has two objectives to contribute to filling this gap: (1) to research the main challenges that make it difficult to improve urban drainage systems; and (2) to prioritize them. We conducted extensive and detailed bibliographic research in which 15 challenges were identified, and a survey with 30 Brazilian professionals with experience in the concerned field. The results showed that 15 challenges identified in the literature were considered important by the survey respondents. It also showed that the most important challenges concern the inadequate functioning of drainage infrastructure, dynamics of city expansion, system maintenance, vulnerability of urban areas, public policies, and investments.

We built an Instant Review System (IRS) for badminton, also named a Challenge System. It allows players to verify linesmen in/out decisions and makes the game fairer. Elements such as lighting, the influence of air-conditioning on the flight trajectory, or the moving mats can significantly impact the final in/out decision. Due to the construction of the shuttlecock, it behaves differently during the flight than, for example, a tennis ball. This publication discusses the problems we encountered during our work with the proposed solution. We present the evolution of the system’s architecture: the first version with the cameras mounted above the court and placed around the court close to the lines, tracking the shuttlecock in 3D; and the second, improved version with cameras placed only around the court, without 3D reconstruction. We used our system during the BWF World Senior Badminton Championships in Katowice. We present the system’s results from this tournament and compare them with linesmen’s decisions. We describe the system’s verification process by the Badminton World Federation and Polish Badminton Federation and discuss evaluation methods for such systems. Our solution is comparable to the commercial product used in the biggest badminton tournaments in regard to processing time and accuracy. Still, our architecture and algorithms make installing it much easier and faster, making the system more adaptive, reliable, flexible, and universal in relation to the practical requirements of sports halls.

A wealth of literature examines the role of challenge from an individual psychological perspective, but research investigating how a talent development system can proactively support athletes to successfully meet the ever-increasing demands of top-level professional sport is less prevalent. This study takes advantage of a naturally occurring but highly atypical developmental challenge as a result of COVID-19 to examine factors influencing the efficacy and effectiveness of the talent development pathway at Munster Rugby. Players and staff (n = 12) took part in semi-structured interviews exploring their experiences of the build-up to the event, the game itself, and the impact post-event. The data were subsequently analysed using Reflexive Thematic Analysis. Players and coaches highlight the groundwork undertaken to establish alignment and coherence, both horizontally and vertically across the talent development environment, and how this contributed to navigating the challenge successfully. The findings support the necessity of both the player and the talent development system being prepared to enable players to perform at the highest level. The findings point to an overlap between the development and performance phases of a player’s journey and the need to integrate short- and long-term objectives within a talent development system.

The Internet of things model enables a world in which all of our everyday devices can be integrated and communicate with each other and their surroundings to gather and share data and simplify task implementation. Such an Internet of things environment would require seamless authentication, data protection, stability, attack resistance, ease of deployment, and self-maintenance, among other things. Blockchain, a technology that was born with the cryptocurrency Bitcoin, may fulfill Internet of things requirements. However, due to the characteristics of both Internet of things devices and Blockchain technology, integrating Blockchain and the Internet of things can cause several challenges. Despite a large number of papers that have been published in the field of Blockchain and the Internet of things, the problems of this combination remain unclear and scattered. Accordingly, this paper aims to provide a comprehensive survey of the challenges related to Blockchain–Internet of things integration by evaluating the related peer-reviewed literature. The paper also discusses some of the recommendations for reducing the effects of these challenges. Moreover, the paper discusses some of the unsolved concerns that must be addressed before the next generation of integrated Blockchain–Internet of things applications can be deployed. Lastly, future trends in the context of Blockchain–Internet of things integration are discussed.

Background: The identification of biomarkers associated with delirium in the emergency department could contribute to the understanding, prediction and diagnosis of this disorder. The present study was carried out to identify biomarkers included in easily and quickly obtained standard blood examinations in older patients with delirium in the emergency department. Methods: A case–control study was carried out in the emergency department of Francesc de Borja Hospital (Gandía, Valencia, Spain). Older adults (≥65 years of age) diagnosed with delirium (n = 128) were included. Cases due to alcohol or substance abuse were excluded. Controls were selected on a randomized basis from the remaining patients (n = 128). All laboratory test parameters included in the routine blood and urine tests of the emergency department were collected. Results: The mean age of the patients was 81.24 ± 7.51 years, and 56.2% were males, while the mean age of the controls was 78.97 ± 7.99 years, and 45.3% were males. Significant differences were found between the cases and controls in relation to the following parameters: urea 43 (32–58) mg/dL versus 50 (37–66) mg/dL, respectively; neutrophils 69.6 (62.05–78.75)% versus 75.5 (65.1–83.2)%; monocytes 8.7 (7–10.4)% versus 7.6 (5.5–9.2)%; platelets 213 (159–266) × 109/L versus 224 (182–289) × 109/L; neutrophil–lymphocyte ratio 3.88 (2.45–7.07) versus 5 (2.75–8.83); platelet–lymphocyte ratio 281.4 (210–360) versus 357.1 (257.8–457.1); and mean platelet volume 10.6 (10–11.5) fl versus 10.4 (9.67–10.9) fl. Although the mean values were above desirable levels in both groups, they were higher for most parameters in the control group. No significant differences were observed in C-reactive protein concentration (9.99 (1.69–51) mg/L versus 12.3 (3.09–65.97) mg/L). Conclusions: The identification of delirium biomarkers poses difficulties due to the urgent nature of the disorders found in older people admitted to the emergency department. Research in this field is needed, since it would allow early identification and treatment of delirium.

Phosphorylation is an essential process in biological events and is considered critical for biological functions. In tissues, protein phosphorylation mainly occurs on tyrosine (Tyr), serine (Ser) and threonine (Thr) residues. The balance between phosphorylation and dephosphorylation is under the control of two super enzyme families, protein kinases (PKs) and protein phosphatases (PPs), respectively. Although there are many selective and effective drugs targeting phosphokinases, developing drugs targeting phosphatases is challenging. PTP1B, one of the most central protein tyrosine phosphatases (PTPs), is a key player in several human diseases and disorders, such as diabetes, obesity, and hematopoietic malignancies, through modulation of different signaling pathways. However, due to high conservation among PTPs, most PTP1B inhibitors lack specificity, raising the need to develop new strategies targeting this enzyme. In this mini-review, we summarize three classes of PTP1B inhibitors with different mechanisms: (1) targeting multiple aryl-phosphorylation sites including the catalytic site of PTP1B; (2) targeting allosteric sites of PTP1B; (3) targeting specific mRNA sequence of PTP1B. All three types of PTP1B inhibitors present good specificity over other PTPs and are promising for the development of efficient small molecules targeting this enzyme.

Nervous necrosis virus (NNV) can cause enormous economic losses in mariculture. Vaccines are promising ways to control the disease. In this study: the interferon regulatory factor 3 (IRF3) gene of pearl gentian grouper was cloned and functionally analyzed; then a bicistronic DNA vaccine encoding both capsid protein (CP) and IRF3 was constructed; then the cellular, humoral, and local immune responses in the grouper after immunization were investigated; and then the protective effects after the NNV challenge were investigated. The results showed that the vaccine successfully expressed CP and IRF3. After immunization, the lymphocytes were recruited at the injection site in the muscles. The percentage of sIgM+ lymphocytes in the head, kidney, and spleen significantly increased and peaked at 28.8 ± 3.1% and 42.6 ± 4.2% at the 3rd to 4th weeks. Six immune-related genes were significantly up-regulated. In the meantime, the total antibodies, anti-NNV specific antibodies, and neutralizing antibody titers in serum increased. After the challenge with 105, 106 or 107 TCID50/fish, the relative percent survival rate was 81.25%, 73.91%, and 66.67%, respectively. In 106 TCID50/fish groups, the percentages of sIgM+ lymphocytes, antibodies, and the viral load were investigated. In conclusion, the bicistronic vaccine significantly induced humoral and cellular responses in pearl gentian grouper and provided effective protection against NVV infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the prime challenge facing public health safety since 2019. Correspondingly, coronavirus disease 2019 (COVID-19) vaccines have been developed and administered worldwide, varying in design strategies, delivery routes, immunogenicity and protective efficacy. Here, a replication-competent vesicular stomatitis virus (VSV) vectored recombinant COVID-19 vaccine was constructed and evaluated in BALB/c mice and Syrian golden hamsters. In BALB/c mice, intramuscular (i.m.) inoculation of recombinant vaccine induced significantly higher humoral immune response than that of the intranasal (i.n.) inoculation group. Analyses of cellular immunity revealed that a Th1-biased cellular immune response was induced in i.n. inoculation group while both Th1 and Th2 T cells were activated in i.m. inoculation group. In golden hamsters, i.n. inoculation of the recombinant vaccine triggered robust humoral immune response and conferred prominent protective efficacy post-SARS-CoV-2 challenge, indicating a better protective immunity in the i.n. inoculation group than that of the i.m. inoculation group. This study provides an effective i.n.-delivered recombinant COVID-19 vaccine candidate and elucidates a route-dependent manner of this vaccine candidate in two most frequently applied small animal models. Moreover, the golden hamster is presented as an economical and convenient small animal model that precisely reflects the immune response and protective efficacy induced by replication-competent COVID-19 vaccine candidates in other SARS-CoV-2 susceptible animals and human beings, especially in the exploration of i.n. immunization.

(1) Background: The interpersonal dimensions of coaching in high performance sport have been subject to increasing scrutiny but with limited evidence to guide practice. Similarly, there is increasing practical interest in the concept of psychological safety, often portrayed as an implicitly desirable characteristic of all sporting environments but, as yet, still to receive research attention in high performance. As a first step to addressing these deficiencies, the present study addressed two research aims: (a) to examine the extent to which matched groups of international and released professional rugby union players perceived psychological safety to be an adaptive feature of their developmental experience and (b) to understand what elements of the player’s coaching experience were perceived to be enabling or disenabling of future progress. (2) Methods: Seven rugby union players who had ‘made it’ and eight players who had been released from their professional contracts took part in a semi-structured interview exploring their developmental experiences. Data were subsequently analysed using Reflexive Thematic Analysis. (3) Results: Both groups of players found each of their talent development and high performance environments to be psychologically unsafe. Furthermore, players perceived coaches who were the most impactful in their development as offering ‘tough love’. This included a range of ‘harder’ and ‘softer’ interpersonal approaches that presented the player with clear direction, role clarity and a sense of care. It appeared that this interpersonal approach helped the player to navigate, and benefit from, the psychologically unsafe high performance milieu. (4) Conclusions: There appear to be a number of balances for the coach in the high performance setting to navigate and a need for more nuance in applying constructs such as psychological safety.

(1) Background: There is abundant literature in talent development investigating the relative age effect in talent systems. There is also growing recognition of the reversal of relative age advantage, a phenomenon that sees significantly higher numbers of earlier born players leaving talent systems before the elite level. However, there has been little investigation of the mechanisms that underpin relative age, or advantage reversal. This paper aimed to investigate (a) the lived experience of relative age in talent development (TD) systems, (b) compare the experience of early and late born players, and (c) explore mechanisms influencing individual experiences. (2) Methods: interviews were conducted with a cohort of near elite and elite rugby union players. Data were subsequently analysed using reflexive thematic analysis and findings considered in light of eventual career status. (3) Results: challenge was an ever-present feature of all players journeys, especially at the point of transition to senior rugby. Psycho-behavioural factors seemed to be a primary mediator of the response to challenge. (4) Conclusions: a rethink of approach to the relative age effect is warranted, whilst further investigations of mechanisms are necessary. Relative age appears to be a population-level effect, driven by challenge dynamics.

Bacteriophages, which are viruses with restricted tropism for bacteria, have been employed for over a century as antimicrobial agents; they have been largely abandoned in Western countries but are constantly used in Eastern European countries with the advent of antibiotics. In recent decades, the growing spread of multidrug-resistant bacteria, which pose a serious threat to worldwide public health, imposed an urgent demand for alternative therapeutic approaches to antibiotics in animal and human fields. Based on this requirement, numerous studies have been published on developing and testing bacteriophage-based therapy. Overall, the literature largely supports the potential of this perspective but also highlights the need for additional research as the current standards are inadequate to receive approval from regulatory authorities. This review aims to update and critically revise the current knowledge on the application of bacteriophages to treat bacterial-derived infectious diseases in animals in order to provide topical perspectives and innovative advances., Competing Interests: The authors declare no conflicts of interest.

Vaccination against the Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is widely practiced in both sows and piglets. However, it has been shown that multivaccinated sows sometimes lack a detectable antibody response, testing seronegative in ELISA (non-responders). Moreover, PRRSV-vaccinated piglets can remain seronegative as well, which is mainly attributed to the interference of maternally derived antibodies (MDAs). The current study investigated the impact of the sow's immune status on the PRRSV vaccine effectiveness in the progeny. The experimental trial included forty-eight piglets ( n = 48) originating from a commercial Belgian breeding herd, with twenty-four piglets born from PRRSV vaccinated responder sows (E+ piglets) and twenty-four piglets born from PRRSV vaccinated non-responder sows (E- piglets). Eight piglets in each group were either non-vaccinated (NoVac piglets; n = 8), intramuscularly vaccinated (IM piglets; n = 8), or intradermally vaccinated (ID piglets; n = 8), with the same PRRSV-1 vaccine as used in the sow population. Vaccination was performed at weaning at three weeks of age, and all study piglets were challenged with a high dose of the PRRSV-1 07V063 strain at 6 weeks of age. A clear interference of MDAs was observed in the E+ piglets: 66.7% of the vaccinated E+ piglets lacked an antibody response at 3 weeks post-vaccination (non-responders). Consequently, post-challenge, only the responding E+ piglets had a significantly reduced serum viremia compared to the E+ NoVac piglets. The observed viremia in the non-responding E+ piglets was similar to the viremia of the E+ NoVac piglets. In the vaccinated E- piglets, a lack of antibody response at 3 weeks post-vaccination was observed in 18.8% of the piglets. Interestingly, despite the lack of a vaccine antibody response, the non-responding E- piglets had a significantly reduced serum viremia compared to the NoVac E- piglets. In contrast, the viremia of the responding E- piglets was only numerically reduced compared to the NoVac E- piglets. Finally, some clear differences were observed in both the kinetics of infection and the immune responses post-challenge between the E+ and E- piglets. The results of this study confirm the consequences of the MDA interference on the induced partial protection of PRRSV vaccination in experimentally challenged piglets. More research is warranted to understand the immunological mechanisms behind MDA interference in PRRSV vaccination and to explain the observed differences between E+ and E- piglets.

The COVID-19 pandemic has become a global problem since first appearing in 2020. Not only does it heavily affect the health sector, but it also spreads to other sectors such as social, economic, and education. Studies have shown that many global companies, including those based in Indonesia, contribute to the global pandemic mitigation by implementing Corporate Social Responsibility (CSR) programs. So far, the implementation of CSR is mainly focused on providing food, medicines, and vitamins, as well as medical facilities and equipment. On the other hand, other reviewed studies showed that the pandemic has transformed the CSR implementation from offline to online, also known as CSR digitalization. The limitation in mobility and strict social distancing rules by the government have resulted in this emergence of CSR digitalization initiatives. Although CSR digitalization is still relatively rare, several technology companies have started implementing it. CSR digitalization practices aim to empower micro, small, and medium enterprises (MSME) to master digital competencies and increase their economic condition affected by the pandemic. Companies implementing CSR digitalization reported a more efficient and effective CSR implementation. This article can potentially introduce a new paradigm to the industry players on the importance of CSR digitalization and future opportunities due to the changes in the behavior of society post-pandemic.

Water policy-making requires the dedicated involvement of all stakeholders, but difficulties remain for the community sector. This study aims to examine the critical challenges of community involvement in water policy decision-making in Thailand. Both qualitative and quantitative methods used in this research project consisted of 39 interviews with informants from a variety of interested parties and 403 community members from around the East Coast River Basin in Thailand completing a survey questionnaire. The results have shown that although mechanisms to enable community involvement in decision-making, such as public consultation and water-related committees, exist, problems remain within the community sector. The critical challenges lie in the opportunities of being consulted and the sharing of power in water policy-making. Although the networks are important, at the same time, they are also obstructing the community sectors in linking their requirements to a final decision, as well as dealing with politics, policy-makers, and staff who organized the process. Therefore, the government should further develop water committee mechanisms by setting up a comprehensive yet practically easy consultation process so that new or inexperienced community members get an opportunity to practice and learn the vital elements necessary in water policy-making. Further research should be conducted in order to compare the opportunities in water decision-making between communities in rural and urban areas. Studies at the local government level should be carried out, with results used as a mechanism to enable community involvement at higher levels of water policy decision-making.

Zika virus (ZIKV), a mosquito-borne flavivirus, has recently triggered global concern due to severe health complications. In 2015, a large ZIKV outbreak occurred in the Americas and established a link between ZIKV and microcephaly in newborn babies, spontaneous abortion, persistent viremia, and Guillain–Barré syndrome. While antivirals are being developed and prevention strategies focus on vector control, a safe and effective Zika vaccine remains unavailable. Messenger RNA (mRNA) vaccine technology has arisen as a flexible, simplified, and fast vaccine production platform. Here, we report on an mRNA vaccine candidate that encodes the pre-membrane and envelope (prM–E) glycoproteins of ZIKV strain Brazil SPH2015 and is encapsulated in lipid nanoparticles (LNPs). Our ZIKV prM–E mRNA-LNP vaccine candidate induced antibody responses that protected in AG129 mice deficient in interferon (IFN) alpha/beta/gamma (IFN-α/β/γ) receptors. Notably, a single administration of ZIKV prM–E mRNA-LNP protected against a lethal dose of ZIKV, while a two-dose strategy induced strong protective immunity. E-specific double-positive IFN-γ and TNF-α T-cells were induced in BALB/c mice after immunizations with a two-dose strategy. With the success of mRNA vaccine technology in facing the coronavirus (COVID-19) pandemic, our data support the development of prM–E RNActive® as a promising mRNA vaccine against Zika to counter future epidemics.

Cancer immunotherapy is becoming more important in the clinical setting, especially for cancers resistant to conventional chemotherapy, including targeted therapy. Chimeric antigen receptor (CAR)-T cell therapy, which uses patient’s autologous T cells, combined with engineered T cell receptors, has shown remarkable results, with five US Food and Drug Administration (FDA) approvals to date. CAR-T cells have been very effective in hematologic malignancies, such as diffuse large B cell lymphoma (DLBCL), B cell acute lymphoblastic leukemia (B-ALL), and multiple myeloma (MM); however, its effectiveness in treating solid tumors has not been evaluated clearly. Therefore, many studies and clinical investigations are emerging to improve the CAR-T cell efficacy in solid tumors. The novel therapeutic approaches include modifying CARs in multiple ways or developing a combination therapy with immune checkpoint inhibitors and chemotherapies. In this review, we focus on the challenges and recent advancements in CAR-T cell therapy for solid tumors.