Critical Priority Research Articles

5.B. Round table: Improving digital health literacy in the era of generative artificial intelligence

Abstract Improved access to generative Artificial Intelligence (AI) platforms and technologies has prompted greater awareness of their potential application in health communication. This workshop will examine this potential alongside the practical challenges and risks of using generative AI in health communication in the broader context of the European Union AI Act. The workshop will explore the implications for the concept of digital health literacy in ways that reduce or mitigate existing digital health inequities across and within Europe. Chatbots and conversational AI platforms such as ChatGPT have opened opportunities for people to find, understand and use health information in significantly different ways. Public health professionals are already using these technologies to simplify health and medical information and to make it available in different languages. AI assisted technologies are also being used to create interactive and engaging learning experiences that provide the public with real-time feedback and insights about their health as well as prompting and reinforcing actions they can take to improve health. These developments have fundamental implications for our understanding of digital health literacy and the methods we use to support people in optimising the potential benefits of AI. Different communities in Europe vary considerably in their - access to digital technology, - skills to discriminate the accuracy and reliability of information, and - trust and responsiveness to what digital technologies have to offer. Building these fundamental digital health literacy skills is a critical priority if we are to ensure that all people benefit equitably from the potential offered by AI. Those of us engaged in improving health literacy have an important role to play in influencing the future direction of AI in health communication, including and especially by engaging in research and development activities that build evidence of effectiveness and support the development of digital health literacy skills in parallel with the expansion of access to AI-assisted digital technologies. The workshop chairs will provide introductory and summary remarks, moderate the panel discussion, and facilitate audience participation in the workshop. The individual panel members will make 3-minute introductions to key issues from different perspectives on the emerging practical applications of generative AI in health communication as well as the implications for strategies to improve digital health literacy in different population groups. The panel is made up of individuals in different roles and at different career stages who can offer complementary perspectives on these issues. Following the presentations, the co-chair will present some follow-up questions to the Panel before engaging directly with the workshop attendees for an open but structured discussion scheduled to last for 30 minutes of the Workshop. Key messages • We will examine how generative artificial intelligence has opened new both new opportunities and risks in the ways people find, understand and use health information. • We will consider how we can optimise the benefits of generative AI in a way that is equitable through the development of digital health literacy within and between communities in Europe. Speakers/panelists Catherine Jenkins London South Bank University, London, UK Diane Levin-Zamir Tel Aviv University, Tel Aviv, Israel Christopher Le Inland Norway University of Applied Sciences, Innlandet, Norway Miguel Telo de Arriaga Direção-Geral da Saúde, Lisbon, Portugal

Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy and future perspectives

Abstract Background/Introduction The fact that hypertrophic cardiomyopathy (HCM) is associated with sudden cardiac death (SCD) due to malignant ventricular arrhythmias underlies its clinical importance (1). SCD in patients with HCM is often an unpredictable event, occurring without previous warning signs or symptoms, and is most common in the young middle-aged group (2). The greatest dilemma in the management of HCM patients is to identify the high-risk population for SCD. The HCM risk- SCD model provides a useful convenience in determining the risk of SCD in patients with HCM even though some patients with low-risk scores still remain at risk of SCD (3). These results have increased the interest in additional strategies to improve the existing risk model. Purpose Hence, the aim of our study was to assess the performance of HCM Risk-SCD in a large series of consecutive patients with HCM who had been followed up in a tertiary centre. Methods The study population consisted of 389 consecutive HCM patients who had been followed up between 2004 and 2021. Demographic and clinical characteristics estimated 5-year risk using the HCM Risk-SCD model were compiled and survival data were collected during follow-up. Patients were divided into 2 groups according to their long-term survival and HCM risk-SCD scores of these two groups were compared. Results The long-term mortality was observed in 47 patients out of 389 patients in the mean follow-up of 55.5 ± 12.7 months. The mean HCM Risk-SCD of surviving patients was significantly lower than that of non-survivors (1.8% vs. 3.0%, p<0.001). The HCM Risk-SCD score was above 6% in 9 (2.6%) survivors and 9 (19.1%) non-survivors (p<0.001). Considering the Kaplan-Meier curve based on the 6% HCM Risk-SCD score, patients at ≥6% risk also had a significantly higher long-term risk of death compared to those with <6% (log-rank test value: 33.72, p<0.001) (Figure 1). The ROC curve based on the HCM Risk-SCD score had 61% sensitivity and 61% specificity for risk for 2.0%, 38% sensitivity and 99% specificity for ≥4%, 17% sensitivity and 99% specificity for ≥6% (Figure 2). Conclusion(s) In conclusion, the current study demonstrates that the HCM risk-SCD model, while easily calculable and clinically useful, does not reliably identify a significant subset of patients with HCM who will potentially be at lifetime risk of SCD. Identifying patients with hypertrophic cardiomyopathy at high risk for SCD who deserve ICD therapy is a critical management priority. A new risk algorithm that can detect the SCD risk of HCM patients with higher sensitivity is needed.Figure 1Figure 2

Discovery of Mycobacterium avium subsp. paratuberculosis Lytic Phages with Extensive Host Range Across Rapid- and Slow-Growing Pathogenic Mycobacterial Species

Background/Objectives: Developing interventions for Johne’s disease, which focuses on controlling Mycobacterium avium subsp. paratuberculosis (MAP) in contaminated environments by treating infected cows and preventing transmission from diseased animals, is a critical priority. Bacteriophage (phage) therapy, an emerging biological intervention, offers a promising alternative for the treatment and management of MAP infections. Methods: In this study, we generated an MAP-specific lytic phage library aimed at characterizing the therapeutic potential of phages under environmental and biological conditions that mimic those encountered in infected cattle such as ruminal fluid, milk, colostrum, and the bovine intestinal epithelium, a key site of MAP colonization and, later, transmission. Results: Our library contains a diverse collection of phages that have demonstrated robust lytic activity against MAP. The host range of these phages was thoroughly assessed, revealing that several isolates produce clear plaques on a range of MAP strains, as well as other pathogenic non-tuberculous mycobacterial (NTM) species and M. tuberculosis strains. This broad host range expands the therapeutic potential of the phage collection, positioning it as a potential cross-species antimicrobial tool. In vitro tests under conditions replicating the rumen, milk, and colostrum environments show that selected phages maintain stability and lytic efficacy, even in the presence of complex biological fluids. Furthermore, a subset of these phages was capable of preventing MAP colonization and invasion in cultured bovine epithelial cells, suggesting their potential for direct prophylactic application in cattle. Conclusions. Our collection of MAP phages represents a valuable source that can be developed into probiotic-like preparations, offering a cost-effective solution for prophylaxis and control of Johne’s disease.

Reverse-transcriptase real-time PCR in the diagnostic strategy for invasive infections caused by Aspergillus fumigatus.

The aim was to develop an RT-qPCR targeting Aspergillus fumigatus and compare its performance to that of Aspergillus fumigatus qPCR for the diagnosis of invasive aspergillosis (IA). Samples from patients of the Lyon University hospitals for whom a suspicion of IA led to the realization of an Aspergillus fumigatus qPCR molecular diagnostic test over a 2-year period were included. The patients were classified according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC-MSGERC) criteria for suspected IA; RT-qPCR and qPCR assays were performed on all included samples. The sensitivities and specificities of RT-qPCR and qPCR were calculated and compared using the results of the EORTC-MSGERC classification as reference. The cycle threshold (Ct) results were compared according to IA classification and sample type. Among the 193 samples analyzed, 91 were classified as IA excluded, 46 as possible IA, 53 as probable IA, and 3 as proven IA. For all sample types, RT-qPCR was significantly more sensitive than qPCR for all IA classifications with an additional 17/102 samples detected (P-value < 0.01). For plasma samples, sensitivity was significantly higher and specificity significantly lower using RT-qPCR for all IA classifications (P-value < 0.001). The mean Ct obtained with RT-qPCR were significantly lower than those obtained with qPCR for all IA classifications and all sample types (P-value < 0.001 and P-value < 0.0001, respectively). RT-qPCR presents a higher sensitivity than qPCR for the diagnosis of IA due to Aspergillus fumigatus, particularly in samples with an intrinsically low fungal load.IMPORTANCEAspergillus fumigatus belongs to the critical priority group of the World Health Organization fungal priority pathogens list. Invasive aspergillosis (IA) is a life-threatening infection with poor prognosis and challenging diagnosis. PCR has been integrated into the 2020 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions for IA diagnosis. However, due to frequent low fungal burdens, its sensitivity needs to be improved. This work presents an innovative method for detecting total nucleic acids, corresponding to both ribosomal RNA and DNA, that enables IA diagnosis with greater sensitivity than conventional techniques, especially in non-invasive samples such as blood, enhancing the monitoring of this infection in high-risk patients.

Enhancing Sustainable Development Competence in Undergraduates: Key Determinants in the Context of “Dual-Carbon” Targets

Sustainable development is vital for achieving balanced progress across the economic, environmental, and health domains, and it is closely tied to the global drive for addressing climate change and environmental challenges. In this context, reaching the “Dual-Carbon” targets—carbon peaking and carbon neutrality—have become critical priorities both domestically and internationally. As a result, the cultivation of Dual-Carbon professionals is essential for driving sustainable development. This paper investigates the sustainable development capacity of Dual-Carbon professionals through an empirical study of 613 undergraduates in China utilizing Astin’s I-E-O theoretical model. This research examines the impact of course experience, self-efficacy, and learning engagement on sustainable development capacity. The results demonstrate that the course experience has a significant positive direct effect on sustainable development capacity. Moreover, self-efficacy mediates the relationship between the course experience and sustainable development capacity, while both self-efficacy and learning engagement serve as chain mediators. Based on these findings, this paper offers practical strategies to enhance the sustainable development capacity of Dual-Carbon undergraduates, providing valuable insights for the education and training of future Dual-Carbon professionals.

The intermediate role of farmland transfer in the impact of digital financial inclusion on agricultural total factor productivity in China

IntroductionEnhancing agricultural productivity and promoting sustainable development in China are critical priorities, given their significant contribution to food security and rural development. However, achieving consistent agricultural productivity growth across regions and sectors has been challenging, leading to inefficiencies and environmental pressures. To address this, the potential of digital inclusive finance (DIF) as a catalyst for progress has been explored.MethodsThis study investigates the impact of DIF on agricultural total factor productivity (ATFP) through farmland transfer, with implications for rural revitalization and high-quality agricultural development. Using the HMB index method, we calculate and decompose China’s inter-provincial ATFP from 2011 to 2020. Employing the dynamic panel fixed effect model and SYS-GMM method, we empirically test the influence of DIF on agricultural productivity in relation to farmland transfer.Results and discussionOur findings reveal a slow upward trend in China’s ATFP, driven primarily by scale efficiency. Notably, a 1% increase in the general index of DIF correlates with a 0.136% increase in ATFP. We analyze the sub-classification indexes of digital inclusive finance, namely coverage breadth, depth of use, and digitalization degree. Their contributions to agricultural productivity growth are significant, with coverage breadth having the greatest impact, followed by depth of use and digitalization degree. Farmland transfer acts as a crucial intermediary, enhancing agricultural allocation efficiency and driving the relationship between digital finance and total factor productivity growth. Interestingly, the western region exhibits the highest growth rates, followed by the eastern region, while the central region shows no significant effects.ConclusionTo comprehensively enhance ATFP, aligning supply and demand for digital financial services, leveraging service depth, and guiding farmland transfer according to local conditions are essential. These findings offer valuable insights into effective strategies for maximizing the potential of DIF, promoting rural development, and achieving sustainable agricultural growth.

Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy

BackgroundMortality from breast cancer is principally due to tumor recurrence. Recurrent breast cancers arise from the pool of residual tumor cells, termed minimal residual disease, that survive treatment and may exist in a dormant state for 20 years or more following treatment of the primary tumor. As recurrent breast cancer is typically incurable, understanding the mechanisms underlying dormant tumor cell survival is a critical priority in breast cancer research. The importance of this goal is further underscored by emerging evidence suggesting that targeting dormant residual tumor cells in early-stage breast cancer patients may be a means to prevent tumor recurrence and its associated mortality. In this regard, the role of autophagy in dormant tumor cell survival and recurrence remains unresolved, with conflicting reports of both pro-survival/recurrence-promoting and pro-death/recurrence-suppressing effects of autophagy inhibition in dormant tumor cells. Resolving this question has important clinical implications.MethodsWe used genetically engineered mouse models that faithfully recapitulate key features of human breast cancer progression, including minimal residual disease, tumor dormancy, and recurrence. We used genetic and pharmacological approaches to inhibit autophagy, including treatment with chloroquine, genetic knockdown of ATG5 or ATG7, or deletion of BECN and determined their effects on dormant tumor cell survival and recurrence.ResultsWe demonstrate that the survival and recurrence of dormant mammary tumor cells following therapy is dependent upon autophagy. We find that autophagy is induced in vivo following HER2 downregulation and remains activated in dormant residual tumor cells. Using genetic and pharmacological approaches we show that inhibiting autophagy by chloroquine administration, ATG5 or ATG7 knockdown, or deletion of a single allele of the tumor suppressor Beclin 1 is sufficient to inhibit mammary tumor recurrence, and that autophagy inhibition results in the death of dormant mammary tumor cells in vivo.ConclusionsOur findings demonstrate a pro-tumorigenic role for autophagy in tumor dormancy and recurrence following therapy, reveal that dormant tumor cells are uniquely reliant upon autophagy for their survival, and indicate that targeting dormant residual tumor cells by inhibiting autophagy impairs tumor recurrence. These studies identify a pharmacological target for a cellular state that is resistant to commonly used anti-neoplastic agents and suggest autophagy inhibition as an approach to reduce dormant minimal residual disease in order to prevent lethal tumor recurrence.

Pathogenesis of Klebsiella Pneumoniae Induced Proteinopathy is Amyloid Strain Dependent

Abstract Introduction/Objective The World Health Organization has labeled Klebsiella pneumoniae (KP), a Gram-negative bacterium, as a ‘Critical Priority’ pathogen due to its increasing prevalence in serious conditions like pneumonia and sepsis, along with its growing resistance to multiple drugs. Infections with KP have been linked to the collapse of microtubules and the release of harmful proteins called amyloid-beta (Aβ) and tau from lung endothelial cells. These infection-induced lung endothelial amyloids can spread like prions and are stable under heat. Methods/Case Report However, the mechanisms behind these effects and whether the infection-generated proteinopathy depends on tau and/or Aβ were not well understood. This study hypothesized that KP infection triggers tau dysfunction, breakdown of microtubules, increased lung barrier permeability, and the production and release of toxic amyloids. To test this, researchers used CRISPR/Cas9 technology to create lung endothelial cells without tau and/or amyloid precursor protein (APP). They confirmed gene deletion through various methods and exposed these cells, along with regular cells, to a highly virulent KP strain. Results (if a Case Study enter NA) The results showed that the KP strain (Kp 1-008) caused disruption of cellular structures, increased permeability, and bacterial spread within hours of infection. Supernatants containing proteins from infected cells, when applied to healthy cells, led to barrier disruption, permeability, and cell death. Interestingly, different pathologies were induced by supernatants from cells lacking tau or APP, indicating that either tau or Aβ alone could propagate damage in a strain- specific manner. The most severe damage required both tau and Aβ together. Conclusion In conclusion, KP infection disturbs cellular structures, promoting barrier breakdown and bacterial dissemination. It also generates toxic tau and Aβ proteins. Either of these proteins can spread harm from cell to cell, but together, they enhance the severity and potency of the resulting lung endothelial protein damage caused by the infection. The study sheds light on the complex mechanisms of KP-related infections and their impact on cellular structures and protein pathways.

Sustainable Logistics: Synergizing Passive Design and PV–Battery Systems for Carbon Footprint Reduction

As more companies strive for net-zero emissions, mitigating indirect greenhouse gas emissions embedded in value chains—especially in logistics activities—has become a critical priority. In the European logistics sector, sustainability and energy efficiency are receiving growing attention, given the sector’s intersectional role in both transportation and construction. This transition toward low-carbon logistics design not only reduces carbon emissions but also yields financial benefits, including operational cost savings and new market opportunities. This study examines the impact of passive design strategies and low-carbon technologies in a Swedish logistics center, assessed using the low-carbon design criteria from the BREEAM International standard, version 6. The findings show that passive energy-efficient measures, such as the installation of 47 skylights for natural daylighting, reduced light power density in accordance with AHSHARE 90.1-2019 and the integration of free night flushing, contribute to a 23% reduction in total energy consumption. In addition, the integration of 600 PV panels and 480 batteries with a capacity of 268 ampere-hours and 13.5 kWh storage, operating at 50 volts, delivers a further 56% reduction in carbon emissions. By optimizing the interaction between passive design and active low-carbon technologies, this research presents a comprehensive feasibility analysis that promotes sustainable logistics practices while ensuring a future-proof, low-carbon operational model.

Current policy and practice for the identification, management, and treatment of postpartum anxiety in the United Kingdom: a focus group study

BackgroundPostpartum Anxiety [PPA] is a prevalent problem in society, posing a significant burden to women, infant health, and the National Health Service [NHS]. Despite this, it is poorly detected by current maternal mental health practices. Due to the current lack of appropriate psychometric measures, insufficiency in training of healthcare professionals, fragmentation of maternal mental healthcare policy and practice, and the magnitude of the effects of PPA on women and their infants, PPA is a critical research priority. This research aims to develop a clear understanding from key stakeholders, of the current landscape of maternal mental health and gain consensus of the needs associated with clinically identifying, measuring, and targeting intervention for women with PPA, in the NHS.MethodsFour focus groups were conducted with a total of 21 participants, via Zoom. Data were analysed using Template Analysis.ResultsAnalysis rendered four main themes: (1) Defining Postpartum Anxiety; (2) Postpartum Anxiety in Relation to other Mental Health Disorders; (3) Challenges to Measurement and Identification of Maternal Mental Health; and (4) An Ideal Measure of Postpartum Anxiety.ConclusionsFindings can begin to inform maternal mental healthcare policy as to how to better identify and measure PPA, through the implementation of a postpartum-specific measure within practice, better training and resources for staff, and improved interprofessional communication.

In vitro activity assessment of cefiderocol against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp., including β-lactam nonsusceptible molecularly characterized isolates, collected from 2020 to 2021 in the United States and European hospitals.

This study reports the activity of cefiderocol against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. isolates collected from the United States and Europe, including Israel and Turkey, from 2020 to 2021. Among Enterobacterales, 2.8% were carbapenem nonsusceptible (CNSE); cefiderocol inhibited 96.6%/85.1% [Clinical Laboratory Standards Institute (CLSI)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints] of these isolates. Imipenem-relebactam, meropenem-vaborbactam, and ceftazidime-avibactam displayed susceptibilities lower than cefiderocol against CNSE isolates (67.4-84.6% susceptible, CLSI). Cefiderocol was the only agent active against CNSE isolates carrying metallo-β-lactamase (MBL) carbapenemase or multiple carbapenemase genes (84.6%-92.3% susceptible, CLSI). Approximately 18% of carbapenem-susceptible Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis carried extended-spectrum-β-lactamases and/or plasmid-borne AmpC-encoding genes; cefiderocol inhibited 99.8%-100.0% (CLSI) of these genotypic groups. Multi-drug resistance (MDR) phenotypes were observed in 16.9% and 52.5% of P. aeruginosa and A. baumannii-calcoaceticus isolates, respectively. Carbapenemase genes were rare (4.9%) among cephalosporin and/or carbapenem nonsusceptible P. aeruginosa, compared to 87.6% carriage in A. baumannii-calcoaceticus, respectively. Against the MDR and carbapenemase-carrying P. aeruginosa and A. baumannii-calcoaceticus subsets, cefiderocol was active against 98.6%/98.7% and 97.1%/97.4% (CLSI), respectively. Only 69 isolates (0.3%) across all species groups were identified as cefiderocol nonsusceptible per CLSI criteria (>4 mg/L). Cefiderocol was the most active agent in vitro against Enterobacterales, P. aeruginosa, and Acinetobacter spp., with uniform activity against all phenotypic- and genotypic-resistant subsets. Coupled with the low incidence of nonsusceptibility observed across species groups, these results demonstrate cefiderocol as an important option for treating infections caused by pathogens with diverse mechanisms of resistance in US and European hospitals.IMPORTANCEThe worldwide spread of multi-drug-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales and Acinetobacter spp. poses a serious challenge in healthcare settings as infections caused by these organisms are commonly refractory to many frontline therapeutic agents. Multiple global health organizations highlighted these pathogens as critical priorities for new antibiotic development, thus necessitating continued surveillance of the activities of currently available antimicrobial agents and circulating mechanisms of resistance. To meet this need, this study phenotypically and genotypically characterized priority Gram-negative pathogens collected from patients in US and European hospitals to examine the activity of cefiderocol and other currently available treatment options, including carbapenems and β-lactam-β-lactamase inhibitor combinations. The results presented here provide a detailed perspective to healthcare practitioners of cefiderocol's broad applicability, manifested in high activity and low nonsusceptibility rates, across phenotypic and genotypic organism groups relative to other agents and further support its use against the most intransigent infections.

Synthesis of kanamycin-azole hybrids and investigation of their antifungal activities

The World Health Organization (WHO) recognizes Candida albicans and Cryptococcus neoformans as the critical priority fungal pathogens for which therapeutic solutions are needed. Azole-based antifungal agents, including triazoles, diazoles, and thiazoles, are widely used in the treatments for fungal infections. In light of past successes in the transformation of antibacterial kanamycin into antifungal derivatives via chemical modifications, a new library of kanamycin-azole hybrids was synthesized and tested against a panel of azole-resistant and susceptible Candida and Cryptococcus strains. Structure activity relationship (SAR) studies revealed pivotal roles for antifungal activity of the azole ring (imidazole vs triazole) and halogen substituents on the benzene ring (F vs Cl). Most notably, hybrids 13, 14 and 15 were active against resistant C. albicans, C. tropicalis and C. neoformans strains and non-toxic towards mammalian cells. Mode of action investigations using fluorogenic dyes, (SYTOXTM) showed the fungal active compounds could permeabilize fungal membranes even at ¼ MICs. These findings reveal novel azole-based antifungals that could offer new therapeutic options for candidiasis and cryptococcosis.

Enrichment Characteristics and Ecological Risk Prediction of Pathogens on Typical Microplastic Biofilms

As an emerging niche colonized by microorganisms, microplastics may selectively enrich pathogens, resulting in crucial ecological risks and potential threats to public health in aquatic environments. However, the enrichment characteristics and ecological risks of pathogens on different microplastic biofilms remain unclear. In this study, 16S rRNA high-throughput sequencing technology was used to investigate the differences in the bacterial community structure, occurrence characteristics of pathogens, and prediction of ecological risks on five typical microplastic biofilms of polyethylene （PE）, polypropylene （PP）, polystyrene （PS）, polyethylene terephthalate （PET）, and polyvinyl chloride （PVC） through a field in-situ incubation experiment. The results showed that after 28 d of in situ incubation, the macroscopic biofilms were formed on the surface of all microplastics, and the diversity and richness of the bacterial community on all microplastic biofilms were higher than in the surrounding water, indicating that the microorganisms in the surrounding water were selectively enriched on microplastics. Each type of microplastic biofilm had formed a unique bacterial community structure； in particular, PVC microplastics were more inclined to selectively enrich the members of Proteobacteria. A total of 47 human pathogens were identified using the HPB database, including six antibiotic resistance pathogens belonging to the lists of critical priority control. The number and total abundance of human pathogens detected on microplastic biofilm were higher than those in the surrounding water, and the dominant pathogens such as Bartonella, Burkholderia, and Brucella were selectively enriched on microplastic biofilms. Microbial phenotype prediction results based on BugBase showed that three functional phenotypes including biofilm formation, mobile element contained, and potentially pathogenic on microplastic biofilms had significantly increased by 2.38%-5.57%, 0.82%-7.13%, and 3.04%-8.30%, respectively, which were mainly contributed by α-Proteobacteria and γ-Proteobacteria. These results not only indicate that the selective enrichment of opportunistic pathogens on microplastic biofilms may lead to the increased risk of pathogenicity and antibiotic resistance co-spread but also provide reference for the accurate assessment of ecological risks caused by microplastic pollution in aquatic environments.

NHS Sussex ICB Urgent Dental Care and Stabilisation Pilot Part 1 - A new approach to addressing a critical patient priority

NHS Sussex ICB Urgent Dental Care and Stabilisation Pilot Part 1 - A new approach to addressing a critical patient priority

Computational Exploration of Limonin as a Potential Inhibitor of DapB in Klebsiella pneumoniae.

Klebsiella pneumoniae has emerged as a significant multidrug-resistant pathogen, classified as a critical priority by the World Health Organization. The rising rates of antibiotic resistance have led to increased therapeutic failures, diminishing the effectiveness of existing antibiotics. Consequently, there is an urgent need for alternative treatments to effectively inhibit the growth of K. pneumoniae and mitigate associated diseases. Phytochemicals have demonstrated potential advantages over traditional antibiotics, prompting their exploration as innovative therapeutic agents. This study aimed to identify phytochemicals that can inhibit dapB, a vital enzyme in the lysine biosynthesis pathway of K. pneumoniae, which is essential for protein synthesis and the cross-linking of the bacterial peptidoglycan cell wall. We screened 17,934 phytochemicals based on Lipinski's Rule of Five, along with their Absorption, Distribution, Metabolism, Excretion properties and toxicological parameters. Next, we conducted triplicate docking studies against dapB to evaluate the library further. The most promising molecules then underwent 100 ns Molecular Dynamics simulations in triplicate, followed by binding free energy calculations to identify potential dapB inhibitors. This in silico analysis highlighted limonin as a promising inhibitor of dapB in K. pneumoniae. Further experimental validation is crucial to enhance limonin's potential as a novel therapeutic agent against K. pneumoniae-associated diseases.

Study on the flame structure and flow field of hydrogen-enriched combustion in array micro-tube

Addressing climate change and reducing greenhouse gas emissions are critical priorities. Utilizing hydrogen-rich methane or pure hydrogen as fuels within gas turbines, facilitated by array micro-tube premixed combustion technology, is anticipated to markedly accelerate the decarbonization process of the energy sector. In this study, the flame structure of the array micro-tube premixed burner under various fuel compositions was examined using OH-Planar Laser-Induced Fluorescence and Particle Image Velocimetry measurement techniques. The effects of the equivalence ratio (φ) and the hydrogen power ratio (HPR) on the characteristics of the flame front, including its curvature, density, volume, and the associated flow field properties, were discussed. As φ and HPR increase, the wrinkled structure of the flame front is significantly enhanced, with a more pronounced effect on smaller scales. This enhancement leads to the separation of the unburned pockets from the main flame. Concurrently, both the flame length and the flame area decrease with the augmentation of φ and HPR, indicating a more concentrated combustion process and increased combustion intensity under hydrogen-enriched and pure hydrogen conditions. The study also observed a slight increase in both the negative and positive curvatures of the flame front, with a more notable increase in the negative curvature. The increased negative curvature results in an elevated degree of wrinkling and a higher value of Σ (flame surface density), reaching a maximum of 0.876 mm−1 under the conditions where φ is 0.8 and ⟨c⟩ (mean progress variable) is 0.5, resulting in the smallest observed flame volume of 100.6 mm3. Upon coupling the flame with the flow field, it was discovered that the exit flow field of the array micro-tube exhibits symmetry and a characteristic conical flame shape. The burning velocity of the side flame brushes increases, and the velocity peak shifts upstream. The aforementioned findings confirm that the addition of hydrogen increases the laminar flame velocity, enabling the flame to stably anchor to the microtube outlet and thereby enhance the flame's robustness and stability.

Neutralizing antibody titers after COVID-19 vaccination

BackgroundMonitoring COVID-19 and evaluating the effectiveness of prevention and control strategies are considered critical priorities in public health. As a result, the administration of COVID-19 vaccines has been widely approved around the world. In the current study, we investigated the level of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) neutralizing antibody (NAb) among individuals who received different COVID-19 vaccines. MethodsThis cross-sectional study recorded demographical data and clinical characteristics of 168 individuals who received COVID-19 vaccines from 2021 to 2022. Vaccination data of participants, including type and times of vaccine and any complications and symptoms after vaccination, were also recorded. SARS-CoV-2 NAb level was assessed by performing an ELISA test, and all data was analyzed using SPSS version 21. The significant level was set at 0.05. ResultsThe mean age of the participants was 40.4 ± 16 years, and 109 were females. About 18.4% of participants had the underlying diseases, of which thyroid diseases were the most frequent. The mean SARS-CoV-2 NAb level was 31.6 ± 39.78 ng/ml. Sinopharm was the common vaccine in our population, and AstraZeneca represented a high level of Nab 47.18 ng/ml. Among the participants, 96 had mild to severe complications after vaccination, with the most complaining of arm pain. Significant differences of NAb levele were observed only between types of vaccine and gender (P<0.05). ConclusionDue to our findings, all employed vaccines demonstrated efficacy in generating NAb. The levels of Nab were different among genders, age groups, and different types of vaccine receivers.

Wood-based policies as a driver for the climate transition

Abstract In the context of global accelerating urbanization, the total floor area of buildings is expected to double by 2060, with a significant impact on the environment. While cities made consistent progress towards increasing energy efficiency, accounting for, and reducing embodied emissions for new and renovated constructions represents one critical priority for mitigating this impact and reaching genuine carbon neutrality. Wood is a renewable and carbon-positive material, which can have a meaningful contribution to changing paradigms on net-zero carbon ambitions of cities, but still faces the challenge of an immature integration into urban development policy framework. Through the Horizon 2020 “Build-in-Wood” project we addressed the challenge of translating novel wood building systems, pilots, wood value chains for the construction of multi-storey wood buildings, and promising practices into policy. As a result, we formulate transferable lessons learned, recommendations, and criteria that can serve as guidance for municipalities and policymakers who aim to channel their efforts toward creating a more sustainable built environment by prioritizing wood, either implicitly or explicitly. We achieved this by working on understanding the real needs of cities and territories, the drivers, and the key entry points and preconditions for new policies supporting multi-storey wood buildings and genuine carbon neutrality. Specifically, the findings are based on the close collaboration with seven affiliated cities (Early Adopter Cities in Europe), outlining and integrating the results of (i)Multi-criterial urban planning, strategic and regulatory context analysis, (ii)Participatory and co-design approaches implemented with their local stakeholder ecosystem from the wood construction value chains and (iii)Research of different best practice policies at national, regional and local level from different parts of the globe, that incentives through informative, financial, research or regulatory instruments building with wood. The entire process is presented in the form of a Build-in-Wood Policy Catalogue [1], offering insights on working with Early Adopter Cities and guidance for improving policy, governance, and the decision-making process for subnational governments. The research was not intended to be exhaustive in documenting all existing policies because of the field’s dynamics, but rather to provide an overview and understanding of different policy instruments’ applicability and potential impact.

Role of Energy Intensity and Investment in Reducing Emissions in Türkiye

Addressing the challenge of rising carbon dioxide (CO2) and greenhouse gas (GHG) emissions is a critical priority in global efforts to combat climate change. The primary aim is to assess the relationship between energy intensity, private investments in energy, renewable energy consumption, export-related factors, and their influence on CO2 and GHG emissions in Turkey. The study employs a multi-level approach using correlation and regression analyses to explore the impact of the selected variables. A Bayesian correlation analysis was conducted to evaluate the strength of relationships between variables, and a regression model was used to test the significance of each factor. Data were gathered from official sources on energy intensity, renewable energy consumption, private investments in energy, and export-related variables in Turkey from 2007 to 2022. The study employed the JASP statistical software. The analysis showed that energy intensity and private energy investments are the most significant predictors of CO2 and GHG emissions. Energy intensity exhibited a strong negative correlation with CO2 emissions per capita (r = -0.717, BF₁₀ = 10.456) and GHG emissions (r = -0.802, BF₁₀ = 44.224), highlighting the critical role of energy efficiency in reducing emissions. Renewable energy consumption also played a role, though its influence was less pronounced than energy efficiency and investment. Based on the findings, it is recommended that policymakers prioritize energy efficiency improvements and create incentives for private investment in renewable energy technologies. Future studies should focus on sector-specific energy efficiency improvements and policy frameworks to enhance private sector engagement in clean energy initiatives.

Microbiome-derived antimicrobial peptides show therapeutic activity against the critically important priority pathogen, Acinetobacter baumannii.

Acinetobacter baumannii is designated by the World Health Organisation as a critical priority pathogen. Previously we discovered antimicrobial peptides (AMPs), namely Lynronne-1, -2 and -3, with efficacy against bacterial pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. Here we assessed Lynronne-1, -2 and -3 structure by circular dichroism and efficacy against clinical strains of A. baumannii. All Lynronne AMPs demonstrated alpha-helical secondary structures and had antimicrobial activity towards all tested strains of A. baumannii (Minimum Inhibitory Concentrations 2-128 μg/ml), whilst also having anti-biofilm activity. Lynronne-2 and -3 demonstrated additive effects with amoxicillin and erythromycin, and synergy with gentamicin. The AMPs demonstrated little toxicity towards mammalian cell lines or Galleria mellonella. Fluorescence-based assay data demonstrated that Lynronne-1 and -3 had higher membrane-destabilising action against A. baumannii in comparison with Lynronne-2, which was corroborated by transcriptomic analysis. For the first time, we demonstrate the therapeutic activity of Lynronne AMPs against A. baumannii.