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This study investigates the presence of Trichuris trichiura eggs in soil samples collected from urban areas in Lahore, Pakistan. A total of 3600 soil samples were collected over two years from Lahore’s urban regions. The detection of helminth eggs in these samples was performed using sodium hypochlorite (NaOCl) as a diagnostic technique. The study reveals an overall prevalence rate of T. trichiura at 0.97 % (35 out of 3600) in the contaminated soil samples from Lahore’s slum areas. When analyzing the data by geographical areas, the study found the highest prevalence of T. trichiura in Allama Iqbal Town (1.83 %, 11 out of 600), followed by Samanabad (1.16 %, 7 out of 600), Wapda Town (1.00 %, 6 out of 600), Gulberg (1.00 %, 6 out of 600), and Cantt (0.50 %, 3 out of 600). Conversely, Valencia Town had the lowest prevalence rate at 0.33 % (2 out of 600). However, these variations in prevalence rates were not statistically significant (p = 0.117). Prevalence rates of T. trichiura’s eggs varied significantly across different sampling seasons (p>0.001). In autumn, a total of 900 soil samples were collected, with 19 samples (2.11 %) testing positive for T. trichiura. This rate was notably higher compared to the prevalence rates observed in winter, spring, and summer, which were 0.66 %, 0.22 %, and 0.88 %, respectively. Regarding the sampling months, the study observed a significantly higher prevalence during September (3.33 %, 10 out of 300), followed by October (2.33 %, 7 out of 300), and August (1.33 %, 4 out of 300). Prevalence rates gradually decreased in other months, ranging from 1 % to 0.33 % (3 to 1 out of 300), with no parasite detection in March (0 %, 0 out of 300) (p < 0.001). This research underscores soil contamination due to fecal waste and highlights public unawareness of parasite biology, driven by open defecation practices.

Rita Vaz-Rodrigues,1 Lorena Mazuecos,1 José de la Fuente1,2 1SaBio (Health and Biotechnology), Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ciudad Real, 13005, Spain; 2Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USACorrespondence: José de la Fuente, SaBio (Health and Biotechnology), Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ronda de Toledo s/n, Ciudad Real, 13005, Spain, Tel +34 926 295 151, Email jose_delafuente@yahoo.comAbstract: The α-Gal syndrome (AGS) is a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in foods containing the oligosaccharide galactose-α-1,3-galactose (α-Gal) such as mammalian meat or dairy products. Clinical presentation of AGS can also comprise immediate hypersensitivity due to anticancer therapy, gelatin-containing vaccines or mammalian serum-based antivenom. The IgE initial sensitization is caused by hard-bodied tick bites and symptomatic individuals typically develop delayed pruritus, urticaria, angioedema, anaphylaxis, malaise or gut-related symptoms. Due to inapparent presentation, delayed reactions and a wide variety of patients´ clinical history, the AGS diagnosis and treatment remain challenging. This review covers not only current diagnostic methods used for AGS such as the skin prick test (SPT), the oral food challenge (OFC), anti-α-Gal IgE levels measurement and the basophil activation test (BAT), but also potentially relevant next-generation diagnostic tools like the mast cell activation test (MAT), the histamine-release (HR) assay, omics technologies and model-based reasoning (MBR). Moreover, it focuses on the therapeutical medical and non-medical methods available and current research methods that are being applied in order to elucidate the molecular, physiological and immune mechanisms underlying this allergic disorder. Lastly, future treatment and preventive tools are also discussed, being of utmost importance for the identification of tick salivary molecules, with or without α-Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development. Bearing in mind climate change, the tick-host paradigm will shift towards an increasing number of AGS cases in new regions worldwide, which will pose new challenges for clinicians in the future.Keywords: alpha-Gal syndrome, AGS, food allergy, alpha-Gal, glycan, tick, IgE

This technical report is based on the study for the evaluation of the processes of reuse and recycling of reverse osmosis components and membranes in the Canary Islands and Macaronesia, within the DESAL+ project and in the framework of the DESAL+ LIVING LAB platform, coordinated by the Canary Islands Technological Institute (ITC) and the Canary Islands Agency for Research, Innovation and Information Society (ACIISI), with the support of the Interreg-MAC Programme. Reverse osmosis membranes could be reused in the same or another desalination plant by replacing the membranes in the first, dirtier positions with those in the last, less damaged positions. Also, by changing the best first-stage membranes to the second and vice versa, the useful life of these membranes could be extended through chemical cleaning and a second life could be given in tertiary treatment plants, reuse in industrial processes where they use special reverse osmosis membranes and degrade rapidly, in processes with leachate from landfill waste and also an interesting option is the oxidation of reverse osmosis elements to obtain nanofiltration, ultrafiltration or microfiltration membranes for the removal of physical dirt. The main categories of thermal processing recycling commonly used in industry include incineration and pyrolysis to produce energy, gas and fuel. These processes can be applied to mixed plastic waste, such as the combination of materials used in the manufacture of reverse osmosis membranes. The recycling of reverse osmosis elements from desalination plants is shown as an opportunity, nowadays existing pioneering initiatives in Europe. Energy recovery, via incineration, is feasible but is not considered in accordance with the environmental, social and political problems that this may generate. However, the recycling of the reverse osmosis elements via pyrolytic industry for fuel production can be centralized in a new industry already planned in the Canary Islands and all the osmosis membranes that are obsolete can be sent there. This is a technically and economically viable business opportunity with a promising future in today's recycling market as studied in the technical report. [ABSTRACT FROM AUTHOR]

The growing demand for clean and efficient fuels in the world reflects the rapid growth in automotive vehicles and more stringent environmental regulations. Hence, the refining industry must employ diverse strategies to obtain a gasoline pool made up of streams from different processes focused on improving the fuel quality and the octane ratings suitable for the current demanding automotive performance. The composition of gasoline varies mainly from each country's policies, climate, environmental regulations, financial capacity, and local producer's oil refining infrastructure. However, a generally accepted composition by source of the gasoline pool is: FCC naphtha and reformate, making up about 60%, light straight-run naphtha and alkylate gasoline, around 30%, isomerate, close to 5%, and variable proportions of butane, oxygenating agents, such as methyl-ter-butyl ether (MTBE), ter-amyl-methyl ether (TAME) and/or ethanol and additives for the remaining 5%. This review is focused on the recent research in the advancement and development of catalysts for the different processes used by the oil refining industry to improve the composition and properties of gasoline fuels. A detailed section on the Fischer-Tropsch process, where liquid hydrocarbons are potentially employed to further produce clean gasoline, is also discussed. A section devoted to research on biogasoline as a potential renewable fuel is also addressed. Finally, a discussion of the physicochemical properties of the gasoline blending components is also provided. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the commonest cancers with high morbidity and mortality in the world. How to realize precise diagnosis and therapy of GC owns great clinical requirement. In recent years, artificial intelligence (AI) has been actively explored to apply to early diagnosis and treatment and prognosis of gastric carcinoma. Herein, we review recent advance of AI in early screening, diagnosis, therapy and prognosis of stomach carcinoma. Especially AI combined with breath screening early GC system improved 97.4 % of early GC diagnosis ratio, AI model on stomach cancer diagnosis system of saliva biomarkers obtained an overall accuracy of 97.18 %, specificity of 97.44 %, and sensitivity of 96.88 %. We also discuss concept, issues, approaches and challenges of AI applied in stomach cancer. This review provides a comprehensive view and roadmap for readers working in this field, with the aim of pushing application of AI in theranostics of stomach cancer to increase the early discovery ratio and curative ratio of GC patients.

BACKGROUND Exagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis through ex vivo clustered regularly interspaced short palindromic repeats (CRJSPR)-Cas9 gene editing of the erythroid-specific enhancer region of BCL11A in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs). METHODS We conducted an open-label, single-group, phase 3 study of exa-cel in patients 12 to 35 years of age with transfusion-dependent β-thalassemia and a β0/β0, β0/β0-like, or non-ββ0/β0-like genotype. CD34+ HSPCs were edited by means of CRISPR-Cas9 with a guide mRNA. Before the exa-cel infusion, patients underwent myeloablative conditioning with pharmacokinetically dose-adjusted busulfan. The primary end point was transfusion independence, defined as a weighted average hemoglobin level of 9 g per deciliter or higher without red-cell transfusion for at least 12 consecutive months. Total and fetal hemoglobin concentrations and safety were also assessed. RESULTS A total of 52 patients with transfusion-dependent β-thalassemia received exa-cel and were included in this prespecified interim analysis; the median follow-up was 20.4 months (range, 2.1 to 48.1). Neutrophils and platelets engrafted in each patient. Among the 35 patients with sufficient follow-up data for evaluation, transfusion independence occurred in 32 (91%; 95% confidence interval, 77 to 98; P<0.001 against the null hypothesis of a 50% response). During transfusion independence, the mean total hemoglobin level was 13.1 g per deciliter and the mean fetal hemoglobin level was 11.9 g per deciliter, and fetal hemoglobin had a pancellular distribution (>94% of red cells). The safety profile of exa-cel was generally consistent with that of myeloablative busulfan conditioning and autologous HSPC transplantation. No deaths or cancers occurred. CONCLUSIONS Treatment with exa-cel, preceded by myeloablation, resulted in transfusion independence in 91% of patients with transfusion-dependent β-thalassemia. (Supported by Vertex Pharmaceuticals and CRISPR Therapeutics; CLIMB THAL-111 ClinicalTrials.gov number, NCT03655678.) [ABSTRACT FROM AUTHOR]

The effects of including almond hulls (AH) in the concentrate fed to light lambs on animal performance, diet utilization, and blood metabolites. Three isonitrogenous and isoenergetic concentrates were formulated with either 0 (control), 6 (AH6) or 12 (AH12) g of AH per 100 g (fresh matter basis). Thirty Manchega breed lambs (15 males and 15 females; 12.3 ± 0.18 kg body weight (BW)) were distributed into six homogeneous groups according to BW (3 groups of each sex), which were randomly assigned within sex to each experimental concentrate. Lambs were fed concentrate and barley straw ad libitum until reaching about 23.0 kg BW. There were no differences (P ≥ 0.182) between groups in final BW, intake of concentrate and straw, and feed conversion rate. Average daily gain and digestibility of dry matter and crude protein tended (P < 0.10) to decrease by the AH inclusion in the concentrate. Lambs fed AH12 showed greater (P < 0.05) urinary losses than those fed the control concentrate (15.4 and 11.5 g per 100 g of N intake, respectively), despite the similar N intake in all groups. Feeding AH did not affect (P ≥ 0.213) blood concentrations of albumin, globulins, urea, creatinine, glucose, total bilirubin and cholesterol or blood activities of hepatic enzymes. The post-mortem analysis revealed no differences among groups in pH and total volatile fatty acids (VFA) concentrations in the rumen of lambs, but NH 3 -N concentrations were lower (P < 0.05) in the lambs fed the concentrates with AH. In addition, lambs fed AH12 diet had lower (P < 0.05) molar proportions of propionate and greater (P < 0.05) proportions of butyrate compared with lambs fed control and AH6 concentrate. In general, no concentrate x sex interactions were observed, and sex had no effect on the measured parameters except for some differences in ruminal VFA profile. In conclusion, AH can be included at in light lambs' concentrate up to 12 g per 100 g of concentrate without impairing animal growth. • Almond hulls (AH) were evaluated as feed ingredient in concentrates for light lambs 2. • Using up to 120 g/kg of AH did not affect lamb growth, diet digestibility and plasma 3 parameters 4. • Inclusion of 120 g/kg of AH increased N excretion 5. • AH can be used as feed ingredient in light lambs feeding 6. • Optimal level of AH in lambs' diets would depend on nutritional quality of AH 7. [ABSTRACT FROM AUTHOR]

After approval of the Subolesin-based anti-tick vaccine in Uganda, we completed a one-year follow-up evaluation study. The results showed significantly 2.1-5.0-fold higher anti-SUB IgG antibody titers in vaccinated cattle in Mbarara and Maruzi with vaccine effectiveness higher than 95 %. In Mbarara, total number of ticks were 0.8-fold lower in vaccinated cattle with a negative correlation tendency between anti-SUB antibody titers and tick counts. The CCHFV-seropositive cattle significantly decreased in 40 % in SUB-vaccinated animals with a significant positive correlation between CCHFV-seropositive cattle and the total number of ticks per animal and a negative correlation tendency between anti-SUB antibody titers and CCHFV-seropositive cattle. A boosting vaccine dose yearly after primary vaccination with three doses is sufficient to maintain protective antibody titers against ticks and tick-borne diseases affecting human and animal health. These results are relevant for implementation of anti-tick Subolesin-based vaccines in Uganda and other countries in Sub-Saharan Africa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Malaria remains a significant global health challenge, with the deadliest infections caused by Plasmodium falciparum . In light of the escalating drug resistance and the limited effectiveness of available vaccines, innovative treatment approaches are urgently needed. This study explores the potential of the probiotic Limosilactobacillus fermentum YZ01, isolated from traditionally fermented kindirmo milk, to modify host responses to Plasmodium berghei ANKA infection. Twenty-five male BALB/c mice were grouped and administered various treatments, including probiotic-enriched yogurt alone or in combination with antibiotics. Parameters assessed included gut lactic acid bacteria (LAB) composition, parasitaemia progression, survival rates, and immune response dynamics over a 21-day postinfection period. The probiotic treatment significantly altered gut microbiota, evidenced by increased LAB counts and modulated immune responses, notably enhancing IgM and IL-4 production while reducing IFN- γ levels. Mice receiving prolonged probiotic treatment exhibited delayed parasitaemia onset, reduced mortality rates, and a more robust immune response compared to control groups. These outcomes suggest that probiotic intervention not only tempers the pathological effects of malaria but also enhances host resilience against infection. This study underscores the role of gut microbiota in infectious disease pathogenesis and supports probiotics as a promising adjunct therapy for malaria management., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Timothy Bamgbose et al.)

Background: The COVID-19 pandemic adversely affected the severity and prognosis of patients with acute myocardial infarction (MI) caused by atherothrombosis (type 1 MI). The effect, if any, of COVID-19 vaccination and natural SARS-CoV2 serologic immunity in these patients is unclear. Our aim was to analyze the association between the severity and outcome of patients with type 1 MI and their previous SARS-CoV2 vaccination and serostatus., Methods: A single-center retrospective cohort study conducted between March 1, 2020 and March 1, 2023. Clinical and follow-up information was collected from medical records and patients. Total antibodies (IgM, IgA, IgG) to nucleocapsid (N) antigens were measured by ECLIA (electrochemiluminescence-based immunoassay) to test the immune response to natural infection. If positive, IgM and IgG antibodies to spike (S) surface antigens were measured by CLIA to test the immune response to vaccine or natural infection. Multivariable logistic regression analysis was performed, adjusting for age, sex, hypertension, diabetes, and dyslipidemia., Results: Total sample of 949 patients, 656 with ST-segment elevation MI (STEMI) and 293 with non-ST-segment elevation MI (NSTEMI). Mean age was 64 (SD 13) years, 80 % men. Pre-admission vaccination status was: ≥ 1 dose, 53 % of patients; complete vaccination, 49 %; first booster dose, 25 %. The majority (84 %) of vaccines administered were mRNA-based. Six months after MI, 92 (9.7 %) patients had a major adverse cardiac event (MACE) and 50 died; 11 % of patients had severe heart failure or cardiogenic shock (Killip III-IV) after STEMI. Vaccinated patients with STEMI and positive serology (Pos/Vax group) had a higher risk of Killip III-IV on admission: OR 2.63 (1.27-5.44), p = 0.010. SARS-CoV-2 S-specific IgG titers were highest in this group (median > 2080 AU/mL, [IQR 1560- >2080] vs 91 [32-198] in the unvaccinated group). In the overall sample, a higher incidence of 6-month MACE was not demonstrated (OR 1.89 [0.98-3.61], p = 0.055)., Conclusions: The combination of vaccination and natural SARS-CoV2 infection was associated with the development of severe heart failure and cardiogenic shock in patients with STEMI, possibly related to an increased serological response., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ANA BLASCO reports article publishing charges was provided by the Foundation for Biomedical Research of the Hospital Universitario Puerta de Hierro Majadahonda. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tick vaccines are an environmentally friendly intervention for the prevention and control of tick-borne diseases affecting humans and animals worldwide. From our perspective, the challenges in tick vaccinology have encouraged the implementation of new interventions. In this opinion article we propose paratransgenic quantum vaccinology as a new approach that integrates platform trends in biotechnology, such as omics datasets combined with big data analytics, machine learning, and paratransgenesis with a systems biology perspective. This innovative approach allows the identification of protective epitopes in tick- and/or pathogen-derived proteins for the design of chimeric vaccine candidate antigens which can be produced by commensal/symbiotic microorganisms eliciting a protective response in the host., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Tick-borne pathogens pose a major threat to human health worldwide. Understanding the epidemiology of tick-borne diseases to reduce their impact on human health requires models covering large geographic areas and considering both the abiotic traits that affect tick presence, as well as the vertebrates used as hosts, vegetation, and land use. Herein, we integrated the public information available for Europe regarding the variables that may affect habitat suitability for ticks and hosts and tested five machine learning algorithms (MLA) for predicting the distribution of four prominent tick species across Europe., Materials and Methods: A grid of cells 20 km in diameter was prepared to cover the entire territory, containing data on vegetation, points of water, habitat fragmentation, forest density, grass extension, or imperviousness, with information on temperature and water deficit. The distribution of the hosts (162 species) was modelled and included in the dataset. We used five MLA, namely, Random Forest, Neural Networks, Naive Bayes, Gradient Boosting, and AdaBoost, trained with reliable coordinates for Ixodes ricinus , Dermacentor reticulatus , Dermacentor marginatus , and Hyalomma marginatum in Europe., Results: Both Random Forest and Gradient Boosting best predicted ticks and host environmental niches. Our results demonstrate that MLA can identify trait-matching combinations of environmental niches. The inclusion of land cover and land use variables has a superior capacity for predicting areas suitable for ticks, compared to classic methods based on the use of climate data alone., Conclusions: Flexible MLA-driven models may offer several advantages over traditional models. We anticipate that these results may be extrapolated to other regions and combinations of tick-vertebrates. These results highlight the potential of MLA for inference in ecology and provide a background for the evolution of a completely automatized tool to calculate the seasonality of ticks for early warning systems aimed at preventing tick-borne diseases.

Hyalomma anatolicum is a tick of significant one-health importance due to its role as a vector for various pathogens affecting humans, animals and the environment, such as Theileria annulata, which causes tropical theileriosis in cattle, leading to severe economic losses. When infected with pathogens like T. annulata, the salivary glands of H. anatolicum undergo gene expression changes, secrete modified proteins and activate immune responses, all of which facilitate pathogen survival and transmission by modulating the host immune response and optimizing conditions for pathogen development. Understanding these responses is crucial for developing control strategies for tick-borne diseases. To understand the interaction between H. anatolicum and T. annulata, we performed a differential gene expression analysis of H. anatolicum salivary glands. An average of approximately 25 million raw sequencing reads were generated in each replicate using Illumina Sequencing. The sequenced reads were de novo assembled and the assembled transcriptome yielded approximately 50,231 non-redundant transcripts after clustering with CD-HIT using a sequence identity of 95% and alignment coverage of 90%. The assembly quality was evaluated with BUSCO analysis and found to be 86% complete using the Arachnida dataset and then blasted against non-redundant protein sequence database from NCBI followed by counting of reads and differential expression analysis. Overall, around 2400 and 400 genes were found differentially expressed with logFC > 1 and logFC > 2 respectively at FDR < 0.05. Top up-regulated genes included Calpain, Papilin, Neprilysin, and Ankyrin repeat-containing protein. Top down-regulated genes included Scoloptoxin, and Selenoprotein S and other uncharacterized proteins. Many other up-regulated proteins with high significance were uncharacterized suggesting room for further H. anatolicum functional and structural characterization studies. To our best knowledge, this is the first study of H. anatolicum sialotranscriptome which greatly contributes to sialotranscriptome information not only as sequence database but also indicates the potential targets for development of vaccine against ticks and transmission-blocking vaccines against T. annulata., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Infectious diseases are a major threat for human and animal health worldwide. Artificial Intelligence (AI) combined algorithms including Machine Learning and Big Data analytics have emerged as a potential solution to analyse diverse datasets and face challenges posed by infectious diseases. In this commentary we explore the potential applications and limitations of ML to management of infectious disease. It explores challenges in key areas such as outbreak prediction, pathogen identification, drug discovery, and personalized medicine. We propose potential solutions to mitigate these hurdles and applications of ML to identify biomolecules for effective treatment and prevention of infectious diseases. In addition to use of ML for management of infectious diseases, potential applications are based on catastrophic evolution events for the identification of biomolecular targets to reduce risks for infectious diseases and vaccinomics for discovery and characterization of vaccine protective antigens using intelligent Big Data analytics techniques. These considerations set a foundation for developing effective strategies for managing infectious diseases in the future.

Recently, a machine learning molecular de-extinction paleoproteomic approach was used to recover inactivated antimicrobial peptides to overcome the challenges posed by antibiotic-resistant pathogens. The authors showed the possibility of identifying lost molecules with antibacterial capacity, but the other side of the coin associated with catastrophic selection should be considered for the development of new pharmaceuticals.

East Coast fever is a tick-borne theileriosis caused by Theileria parva, a protozoan parasite with the primary vector being the tick Rhipicephalus appendiculatus. This disease poses significant challenges in sub-Saharan Africa, leading to severe economic losses by causing the death of over one million livestock annually. Current control measures include vector control with acaricides and the "infection and treatment" method, which involves immunization with live sporozoites of the pathogen and treatment with long acting oxytetracycline. Despite their effectiveness, these methods face scalability and usability issues, necessitating the development of new prevention strategies, particularly in the field of vaccines for the effective and sustainable control of East Coast fever. In this primer focus, East Coast fever serves as a case study to highlight recent concepts and advancements in tick and tick-borne disease vaccine research. Vaccine design and evaluation processes are reviewed, encompassing the utilization of omics datasets and knowledge on vectors and pathogens, and exploring new design methods, such as quantum vaccinomics and messenger RNA (mRNA)-based vaccines. Key limitations and areas requiring further research are addressed, including insufficient understanding of host-pathogen molecular interactions, the impact of post-translational modifications, and vaccine efficacy variability across different trials. Additionally, new research objectives are proposed to address East Coast fever but with possible impact on other tick-borne diseases. It includes advancing knowledge on tick-pathogen-host molecular interactions, studying tick microbiota, developing novel design approaches, such as combining tick and pathogen epitopes in chimeric vaccines (exemplified by the q38-p67c case), and exploring new immunological enhancers and delivery platforms., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Globally, ticks rank second only to mosquitoes as vectors of deadly pathogens affecting humans and first in transmitting animal pathogens, presenting a significant challenge to human wellness and sustainability of livestock-based industries. Traditional tick control via chemical acaricides impacts on the environment and has led to the emergence of multi-acaricide-resistant tick populations. Use of immunoprophylactic, along with other components of integrated tick management, holds the potential to mitigate tick infestations in a sustainable manner. To control multi-species tick infestations, the concept of a cocktail vaccine comprising of more than one antigens has emerged as a viable solution due to the inconsistent efficacy of single antigen-based immunization protocol., Methods: In this study, a dual antigen cocktail immunization protocol was developed targeting ferritin2 (FER2) and tropomyosin (TPM) proteins, which are associated with ticks' essential cellular and physiological functions, like blood iron homeostasis and muscle contractions., Results: Dual gene silencing of FER2 and TPM genes in Hyalomma anatolicum resulted in a 75.3% reduction in infested ticks, a 95.4% decrease in egg masses, and a complete loss of egg hatching when compared to control ticks. Microscopically, an altered ovarian cellular architecture, marked by vacuolation and reduced nucleus-to-cytoplasmic ratio were noted in the gene knocked down ticks. An immunization with cocktails of 300 µg dose of each protein, rHaFER2 and rHaTPM was standardized in a rat model and was used to immunize cross-bred ( Bos indicus x B. taurus ) male cattle with Montanide ISA 50V2 adjuvant on days 0, 28, and 49. A significant ( p < 0.001) IgG and IgG2 antibody response was observed in the immunized animals with high IgG levels sustained until day 119 post-primary immunization, showing a 4.1-fold increase over the pre-immunization period. The animals were challenged with larvae and adults of H. anatolicum and larvae of Rhipicephalus microplus . Immunization with the cocktail antigen resulted an efficacy of 70% and 76% against H. anatolicum larvae and adults, respectively, and 54% against R. microplus infestations. Compared to single-antigen immunization, the immunization with cocktail antigens demonstrated higher protection against R. microplus and H. anatolicum ticks. The results advance the development of cocktail vaccines to control multiple tick species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Manjunathachar, Kumar, Parthasarathi, Chigure, Saravanan, Sankar, Harish, de la Fuente and Ghosh.)

A measure of lifetime brain atrophy (LBA) obtained from a single magnetic resonance imaging (MRI) scan could be an attractive candidate to boost statistical power in uncovering novel genetic signals and mechanisms of neurodegeneration. We analysed data from five young and old adult cohorts (MRi-Share, Human Connectome Project, UK Biobank, Generation Scotland Subsample, and Lothian Birth Cohort 1936 [LBC1936]) to test the validity and utility of LBA inferred from cross-sectional MRI data, i.e., a single MRI scan per participant. LBA was simply calculated based on the relationship between total brain volume (TBV) and intracranial volume (ICV), using three computationally distinct approaches: the difference ( ICV-TBV ), ratio ( TBV / ICV ), and regression-residual method (TBV~ICV). LBA derived with all three methods were substantially correlated with well-validated neuroradiological atrophy rating scales ( r = 0.37-0.44). Compared with the difference or ratio method, LBA computed with the residual method most strongly captured phenotypic variance associated with cognitive decline ( r = 0.36), frailty ( r = 0.24), age-moderated brain shrinkage ( r = 0.45), and longitudinally-measured atrophic changes ( r = 0.36). LBA computed using a difference score was strongly correlated with baseline (i.e., ICV; r = 0.81) and yielded GWAS signal similar to ICV ( rg = 0.75). We performed the largest genetic study of LBA to date ( N = 43,110), which was highly heritable ( h 2 SNP GCTA = 41% [95% CI = 38-43%]) and had strong polygenic signal (LDSC h 2 = 26%; mean χ2 = 1.23). The strongest association in our genome-wide association study (GWAS) implicated WNT16 , a gene previously linked with neurodegenerative diseases such as Alzheimer, and Parkinson disease, and amyotrophic lateral sclerosis. This study is the first side-by-side evaluation of different computational approaches to estimate lifetime brain changes and their measurement characteristics. Careful assessment of methods for LBA computation had important implications for the interpretation of existing phenotypic and genetic results, and showed that relying on the residual method to estimate LBA from a single MRI scan captured brain shrinkage rather than current brain size. This makes this computationally-simple definition of LBA a strong candidate for more powerful analyses, promising accelerated genetic discoveries by maximising the use of available cross-sectional data.

Crimean-Congo haemorrhagic fever (CCHF) is a widely distributed and potentially fatal tick-borne viral disease with no licensed specific treatments or vaccines. In 2019, WHO published an advanced draft of a research and development roadmap for CCHF that prioritised the development and deployment of the medical countermeasures most needed by CCHF-affected countries. This Personal View presents updated CCHF research and development priorities and is the product of broad consultation with a working group of 20 leading experts in 2023-24. The strategic goals, milestones, and timelines have been revised and expanded to reflect scientific advances since 2019, including the identification of antibodies with therapeutic potential and the progression of four vaccine candidates through phase 1 clinical trials. This update emphasises the need for a One Health approach to manage CCHF, from integrated cross-sectoral surveillance to novel interventions that target ticks and their vertebrate hosts to reduce CCHF virus transmission to humans. The overarching vision for rapid diagnostics and specific therapeutics by 2028, followed by options to limit CCHF virus transmission and control disease by 2030, is deliberately ambitious and will only be achieved through coordinated international action from affected countries, funders, scientists, product developers, manufacturers, regulators, national authorities, and policy makers., Competing Interests: Declaration of interests JF declares a grant from the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación, Spain (grant number MCIN/AEI/10.13039/501100011033) and the EU–European Regional Development Fund (grant number BIOGAL PID2020–116761GB-I00). JF has also received support from the Federal University of Uberlândia and the Brazilian Federal Foundation for Support and Evaluation of Graduate Education (grant number 88887.936876/2024–00) to attend the 2024 Annual Scientific Meeting of the European Veterinary Parasitology College at the University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania. TF declares funding (paid to his institution) from GuardRX (not-for-profit) and the Pandemic Institute (Liverpool) for the UMIT-1 phase 1b Crimean–Congo haemorrhagic fever (CCHF) therapeutics trial in Türkiye; from the Medical Research Council (MRC) for the UMIT-2 phase 2b CCHF therapeutics trial in Türkiye and Iraq; from the MRC for the GeneDrive PCR platform and for development of a CCHF lateral flow test. SG has received grants (paid to his institution) from the German Research Foundation, European Commission, German Government, Coalition for Epidemic Preparedness Innovations (CEPI), and Kirmser Foundation; and has received speaker honoraria and support for attending meetings from WHO and CEPI. RH is in receipt of grant funding from the Biotechnology and Biological Sciences Research Council, the Defense Threat Reduction Agency, and the MRC to investigate CCHF virus genome reassortment, sequence CCHF virus variants, and develop diagnostics for low-resource settings; and is an investigator in the EU H2020-funded CCHFVaccine project. RH is a named inventor on a patent (PCT/GB2013/0503174; WO 2014/132013) for a vectored CCHF vaccine. GKob received federal funding from the Canadian Institute for Health Research to develop immunogens based on CCHF glycoproteins (2016–21), is an inventor on a patent for CCHF virus immunogenic compositions, and received funding from Université Laval and GUARDRx (not-for-profit) to attend meetings related to the original CCHF Research and Development (R&D) Roadmap (2018–20). AC, PCF, PJH, and JPG worked at the Wellcome Trust during the time that the CCHF Roadmap was being revised and this Personal View was written. TJGB, AES, and JW received support from WHO to attend meetings related to the original CCHF R&D Roadmap (2018–20). TJGB, AES, JW, and JO received funding from the Wellcome Trust (grant number 226729/Z/22/Z) to coordinate the 2023–24 update to the CCHF R&D Roadmap and to complete this Personal View. In addition, the Wellcome Trust covered convening costs for TJGB, AES, JW, VB, M-PP, LHB, TF, PBHF, SG, RH, BJ, JF, GP, AP, and HS to attend a meeting of the CCHF working group in London, UK (Feb 13–14, 2023). All other authors declare no competing interests. The authors alone are responsible for the views expressed in this Personal View; they do not necessarily represent the views, decisions, or policies of the institutions with which the authors are affiliated. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Various types of pathogens transmitted by ticks elicit distinct immune responses just like the emerging α-Gal syndrome that is associated with allergic reactions to tick bites. The mechanisms of Neutrophil Extracellular Traps release (called NETosis) and trained immunity in response to tick-borne microbes have not been extensively investigated. In our paper, we explored the intricate interplay of NETosis and trained immunity within the realm of infectious diseases triggered by tick bites and their possible pathogenetic role in autoimmunity. We conducted an extensive literature search to identify studies for this review, considering articles and reviews published in English within the last years. Additionally, we scrutinized the references of all included papers and relevant review articles to ensure comprehensive coverage. We shed light on a plausible correlation between these innate immune responses and their potential implication in certain pathological conditions, with a specific focus on some autoimmune diseases. These findings offer new perspectives for a more profound comprehension of the immunopathogenesis of certain autoimmune-like signs where clinicians should include Tick-Borne Diseases (TBDs) in their differential diagnoses, in those geographical areas of tick infestation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: In previous studies, methylated DNA markers (MDMs) have been identified in pancreatic juice (PJ) for detecting pancreatic ductal adenocarcinoma (PDAC). In this prospective multicenter study, the sensitivity and specificity characteristics of this panel of PJ-MDMs was evaluated standalone and in combination with plasma carbohydrate antigen 19-9 (CA 19-9)., Methods: Paired PJ and plasma were assayed from 88 biopsy-proven treatment-naïve PDAC cases and 134 controls (53 with normal pancreas, 23 with chronic pancreatitis [CP], 58 with intraductal papillary mucinous neoplasm). Bisulfite-converted DNA from buffered PJ was analyzed using long-probe quantitative amplified signal assay targeting 14 MDMs (NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4) and a reference gene (methylated B3GALT6). Logistic regression was used to fit the previously identified 3-MDM PJ panel (FER1L4, C13orf18, and BMP3). Discrimination accuracy was summarized using area under the receiver-operating characteristic curve (AUROC) with corresponding 95% confidence interval (CI)., Results: Methylated FER1L4 had the highest individual AUROC of 0.83 (95% CI, 0.78-0.89). The AUROC for the 3-MDM PJ + plasma CA 19-9 model (0.95; 95% CI, 0.92-0.98) was higher than both the 3-MDM PJ panel (0.87; 95% CI, 0.82-0.92)) and plasma CA 19-9 alone (0.91; 95% CI, 0.87-0.96) (P = .0002 and .0135, respectively). At a specificity of 88% (95% CI, 81%-93%), the sensitivity of this model was 89% (95% CI, 80%-94%) for all PDAC stages and 83% (95% CI, 64%-94%) for stage I/II PDAC., Conclusions: A panel combining PJ-MDMs and plasma CA 19-9 discriminates PDAC from both healthy and disease control groups with high accuracy. This provides support for combining PJ and blood-based biomarkers for enhancing diagnostic sensitivity and successful early PDAC detection., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Evidence on the effectiveness of remdesivir when used in real-life clinical practice is controversial. This study aims to analyse its effectiveness and the factors associated with increased mortality in non-critically ill patients with COVID-19 pneumonia who require supplemental low-flow oxygen and received remdesivir., Methods: A retrospective cohort study was conducted at Ramón y Cajal University Hospital (Madrid, Spain) which included all patients treated with remdesivir in our institution during the second pandemic breakout in Spain, from August to November 2020. Treatment with remdesivir was limited to non-critically ill patients with COVID-19 pneumonia requiring low-flow supplemental oxygen, with a treatment duration of 5 days., Results: A total of 1757 patients were admitted with COVID-19 pneumonia during the study period, of which 281 non-critically ill patients were treated with remdesivir and included in the analysis. Mortality at 28 days after initiation of treatment was 17.1%. The median (IQR) time to recovery was 9 days (6-15). 104 (37.0%) patients had complications during hospitalisation, with renal failure being the most frequent (31 patients; 36.5%). After adjustment for confounding factors, high-flow oxygen therapy was associated with increased 28-day mortality (HR 2.77; 95% CI 1.39 to 5.53; p=0.004) and decreased 28-day clinical improvement (HR 0.54; 95% CI 0.35 to 0.85; p=0.008). A significant difference in survival and clinical improvement was identified between patients treated with high and low-flow oxygen., Conclusion: The 28-day mortality rate in patients treated with remdesivir needing low-flow oxygen therapy was higher than that published in clinical trials. Age and increased oxygen therapy needed after the beginning of treatment were the main risk factors associated with mortality., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease associated with its principal tick vector, Hyalomma spp. with increasing fatal incidence worldwide. Accordingly, CCHF is a World Health Organization-prioritized disease with the absence of effective preventive interventions and approved vaccines or effective treatments. This perspective raised from a multidisciplinary gap analysis considering a One Health approach beneficial for human and animal health and the environment exploring international collaborations, gaps and recommendations., (© 2024. The Author(s).)

Background: Theileria spp. are responsible for ovine and caprine theileriosis, leading to significant morbidity and mortality in small ruminants. The present study aims to investigate Theileria spp. infections in small ruminants from Southern Punjab in Pakistan, and genetic characterize revealed Theileria spp. isolates. Methods: A total of 93 sheep and 107 goats were sampled between May and August 2022. Blood smears were examined microscopically, and PCR amplification targeting the 18S rRNA gene was performed to detect Theileria spp. Additionally, specific PCR assays targeting 18S rRNA and ms1 partial sequences were used to identify Theileria ovis and T. lestoquardi , respectively.  Results: The prevalence of Theileria spp. was significantly higher using PCR (13.5%) compared to microscopic screening (5%). Sheep showed a higher prevalence rate (19.4%) compared to goats (8.4%) ( p = 0.024). Young sheep aged ≤ 1 year were more commonly infected with Theileria spp. (41%) compared to older sheep ( p = 0.006). The prevalence of Theileria spp. was higher in sheep-only herds (37.3%) compared to goat-only herds (18%) or mixed-species herds (8.1%) ( p = 0.015). The prevalence rates of T. ovis and T. lestoquardi were 9% and 2.5%, respectively, with four animals (2 goats and 2 sheep) showing co-infection. Phylogenetic analysis revealed that our T. ovis 18S rRNA sequence clustered with previously reported sequences from sheep in Turkey, China, Spain, and goats in Tanzania. The obtained T. lestoquardi ms1 partial sequence formed a distinct cluster from other T. lestoquardi isolates in Pakistan and neighboring countries.  Conclusion: Theileria spp. co-circulation in Pakistani small ruminants, particularly the presence of T. ovis and T. lestoquardi , highlights the need for attention from animal health decision-makers due to their financial and health impacts.