Materials characterisation and software tools as key enablers in Industry 5.0 and wider acceptance of new methods and products

Recently, the NMBP-35 Horizon 2020 projects -NanoMECommons, CHARISMA, and Easi-stress -organised a collaborative workshop to increase awareness of their contributions to the industry "commons" in terms of characterisation and digital transformation. They have established interoperability standards for knowledge management in characterisation and introduced new solutions for materials testing, aided by the standardisation of faster and more accurate assessment methods. The lessons learned from these projects and the discussions during the joint workshop emphasised the impact of recent developments and emerging needs in the field of characterisation. Specifically, the focus was on enhancing data quality through harmonisation and stand-ardisation, as well as making advanced technologies and instruments accessible to a broader community with the goal of fostering increased trust in new products and a more skilled society. Experts also highlighted how characterisation and the corresponding experimental data can drive future innovation agendas towards tech-nological breakthroughs. The focus of the discussion revolved around the characterisation and standardisation processes, along with the collection of modelling and characterisation tools, as well as protocols for data ex-change. The broader context of materials characterisation and modelling within the materials community was explored, drawing insights from the Materials 2030 Roadmap and the experiences gained from NMBP-35 pro-jects. This whitepaper has the objective of addressing common challenges encountered by the materials com-munity, illuminating emerging trends and evolving techniques, and presenting the industry's perspective on emerging requirements and past success stories. It accomplishes this by providing specific examples and high-lighting how these experiences can create fresh opportunities and strategies for newcomers entering the market. These advancements are anticipated to facilitate a more efficient transition from Industry 4.0 to 5.0 during the industrial revolution

Evaluation of microscopy, serology, circulating anodic antigen (CAA), and eosinophil counts for the follow-up of migrants with chronic schistosomiasis: a prospective cohort study

Background: An accurate test for the diagnosis and post-treatment follow-up of patients with schistosomiasis is needed. We assessed the performance of different laboratory parameters, including the up-converting reporter particle technology lateral flow assay to detect circulating anodic antigen (UCP-LF CAA), for the post-treatment follow-up of schistosomiasis in migrants attending a dedicated outpatient clinic in a non-endemic country.Methods: Routine anti-Schistosoma serology results and eosinophil counts were obtained of patients with positive urine/stool microscopy and/or PCR (confirmed cases) or only positive serology (possible cases), and at least one follow-up visit at 6 (T6) or 12 (T12) months after praziquantel treatment. All sera samples were tested with the UCP-LF CAA assay.Results: Forty-eight patients were included, 23 confirmed and 25 possible cases. The percentage seropositivity and median antibody titers did not change significantly during follow-up. UCP-LF CAA was positive in 86.9% of confirmed and 20% of possible cases. The percentage positivity and median CAA levels decreased significantly post-treatment, with only two patients having positive CAA levels at T12.Conclusions: The UCP-LF CAA assay proved useful for the diagnosis of active infection with Schistosoma spp. and highly valuable for post-treatment monitoring in migrants, encouraging the development of a commercial test.Cancer Signaling networks and Molecular Therapeutic

Cystic echinococcosis in northern Tanzania: a pilot study in Maasai livestock-keeping communities

Background: There are close similarities between the life-cycles of Echinococcus granulosus sensu lato (E. granulosus s.l.) that causes cystic echinococcosis (CE) in humans and Taenia multiceps/Coenurus cerebralis that causes cerebral coenurosis in small ruminants. Recent evidence highlights that livestock in Maasai communities of northern Tanzania are suffering from increases in the prevalence of cerebral coenurosis, leading to concerns about a possible concurrent increased risk of human CE. The aim of this study was to estimate the prevalence of human abdominal CE and the prevalence and species/genotypes of E. granulosus s.l. in livestock in Maasai communities. Methods: Human CE was diagnosed by abdominal ultrasound on volunteers aged ≥ 7 years in five villages in the Longido and Ngorongoro Districts in northern Tanzania. Infection in ruminants was evaluated through inspection in local abattoirs, followed by molecular identification of one cyst per animal, with a priority for hepatic cysts, using PCR targeting of the cytochrome c oxidase I gene (COX1), followed by restriction fragment length polymorphism and multiplex PCR, and sequencing of non-E. granulosus s.l. samples. Results: Ultrasound was performed on 823 volunteers (n = 352 in two villages in Longido District, and n = 471 in three villages of Ngorongoro). Hepatic CE cases were diagnosed only in Ngorongoro (n = 6; 1.3%), of which three had active cysts. Village-level prevalence of CE ranged between 0 and 2.4%. Of the 697 ruminants inspected, 34.4% had parasitic cysts. Molecular identification was achieved for 140 of the 219 (63.9%) cysts sampled. E. granulosus s.l. and T. hydatigena/Cysticercus tenuicollis were identified in 51.4% and 48.6%, respectively, of livestock cysts. E. granulosus s.l. was identified in livestock from both Longido (35.3% of 116 genotyped cysts) and Ngorongoro (91.2% of 34 genotyped cysts). Of the total of 72 E. granuslosus s.l. cysts identified in livestock, 87.5% were E. granulosus sensu stricto (G1–G3 genotypes), 9.7% were E. ortleppi (G5) and one cyst was E. canadensis (G6–10). The three active human cysts, which were removed surgically, were G1–G3 genotypes. Conclusions: Multiple species/genotypes of E. granulosus s.l. are circulating in Maasai communities of northern Tanzania. Human CE was detected in villages of Ngorongoro District and a high prevalence of echinococcal cysts was observed in livestock in both districts. More precise estimation of the prevalence in this area and a better understanding of the specific risk factors for CE among Maasai communities in northern Tanzania is needed. Interventions targeting transmission routes common to both E. granulosus s.l. and T. multiceps would have dual benefits for preventing both human and livestock disease

Field evaluation of an immunochromatographic test for diagnosis of cystic and alveolar echinococcosis

Background: The larval stages of the tapeworms Echinocoocus granulosus and Echinococcus multilocularis are the causative agents of human cystic echinococcosis (CE) and human alveolar echinococcosis (AE), respectively. Both CE and AE are chronic diseases characterised by long asymptomatic periods of many years. However, early diagnosis of the disease is important if treatment and management of echinococcosis patients are to be successful. Methods: A previously developed rapid diagnostic test (RDT) for the differential detection of CE and AE was evaluated under field conditions with finger prick blood samples taken from 1502 people living in the Ganzi Tibetan Autonomous Prefecture, China, a region with a high prevalence for both forms of human echinococcosis. The results were compared with simultaneously obtained abdominal ultrasonographic scans of the individuals. Results: Using the ultrasonography as the gold standard, sensitivity and specificity, and the diagnostic accuracy of the RDT were determined to be greater than 94% for both CE and AE. For CE cases, high detection rates (95.6–98.8%) were found with patients having active cysts while lower detection rates (40.0–68.8%) were obtained with patients having transient or inactive cysts. In contrast, detection rates in AE patients were independent of the lesion type. The positive likelihood ratio of the RDT for CE and AE was greater than 20 and thus fairly high, indicating that a patient with a positive test result has a high probability of having echinococcosis. Conclusions: The results suggest that our previously developed RDT is suitable as a screening tool for the early detection of human echinococcosis in endemic areas

Justified Concern or Exaggerated Fear: The Risk of Anaphylaxis in Percutaneous Treatment of Cystic Echinococcosis—A Systematic Literature Review

Percutaneous treatment (PT) emerged in the mid-1980s as an alternative to surgery for selected cases of abdominal cystic echinococcosis (CE). Despite its efficacy and widespread use, the puncture of echinococcal cysts is still far from being universally accepted. One of the main reasons for this reluctance is the perceived risk of anaphylaxis linked to PTs. To quantify the risk of anaphylactic reactions and lethal anaphylaxis with PT, we systematically searched MEDLINE for publications on PT of CE and reviewed the PT-related complications. After including 124 publications published between 1980 and 2010, we collected a total number of 5943 PT procedures on 5517 hepatic and non-hepatic echinococcal cysts. Overall, two cases of lethal anaphylaxis and 99 reversible anaphylactic reactions were reported. Lethal anaphylaxis occurred in 0.03% of PT procedures, corresponding to 0.04% of treated cysts, while reversible allergic reactions complicated 1.7% of PTs, corresponding to 1.8% of treated echinococcal cysts. Analysis of the literature shows that lethal anaphylaxis related to percutaneous treatment of CE is an extremely rare event and is observed no more frequently than drug-related anaphylactic side effects

The Recognition of N-Glycans by the Lectin ArtinM Mediates Cell Death of a Human Myeloid Leukemia Cell Line

ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus (jackfruit), interacts with N-glycosylated receptors on the surface of several cells of hematopoietic origin, triggering cell migration, degranulation, and cytokine release. Because malignant transformation is often associated with altered expression of cell surface glycans, we evaluated the interaction of ArtinM with human myelocytic leukemia cells and investigated cellular responses to lectin binding. The intensity of ArtinM binding varied across 3 leukemia cell lines: NB4>K562>U937. The binding, which was directly related to cell growth suppression, was inhibited in the presence of Manα1-3(Manα1-6)Manβ1, and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4 cells induced cell death (IC50 = 10 µg/mL), as indicated by cell surface exposure of phosphatidylserine and disruption of mitochondrial membrane potential unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM treatment of NB4 cells strongly induced reactive oxygen species generation and autophagy, as indicated by the detection of acidic vesicular organelles in the treated cells. NB4 cell death was attributed to ArtinM recognition of the trimannosyl core of N-glycans containing a ß1,6-GlcNAc branch linked to α1,6-mannose. This modification correlated with higher levels of N-acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937 cells. Our results provide new insights into the potential of N-glycans containing a β1,6-GlcNAc branch linked to α1,6-mannose as a novel target for anti-leukemia treatment

Materials characterisation and software tools as key enablers in Industry 5.0 and wider acceptance of new methods and products

Recently, the NMBP-35 Horizon 2020 projects - NanoMECommons, CHARISMA, and Easi-stress - organised a collaborative workshop to increase awareness of their contributions to the industry “commons” in terms of characterisation and digital transformation. They have established interoperability standards for knowledge management in characterisation and introduced new solutions for materials testing, aided by the standardisation of faster and more accurate assessment methods. The lessons learned from these projects and the discussions during the joint workshop emphasised the impact of recent developments and emerging needs in the field of characterisation. Specifically, the focus was on enhancing data quality through harmonisation and standardisation, as well as making advanced technologies and instruments accessible to a broader community with the goal of fostering increased trust in new products and a more skilled society. Experts also highlighted how characterisation and the corresponding experimental data can drive future innovation agendas towards technological breakthroughs. The focus of the discussion revolved around the characterisation and standardisation processes, along with the collection of modelling and characterisation tools, as well as protocols for data exchange. The broader context of materials characterisation and modelling within the materials community was explored, drawing insights from the Materials 2030 Roadmap and the experiences gained from NMBP-35 projects. This whitepaper has the objective of addressing common challenges encountered by the materials community, illuminating emerging trends and evolving techniques, and presenting the industry's perspective on emerging requirements and past success stories. It accomplishes this by providing specific examples and highlighting how these experiences can create fresh opportunities and strategies for newcomers entering the market. These advancements are anticipated to facilitate a more efficient transition from Industry 4.0 to 5.0 during the industrial revolution. © 2023The Workshop was supported by EU H2020 project NanoMECommons, GA 952869, CHARISMA, GA 952921, EASI-STRESS, GA 953219, and EsSENce COST ACTION CA19118. This article/publication is based upon work from COST Action EsSENce COST ACTION CA19118, supported by COST (European Cooperation in Science and Technology). Miguel A. Bañares, Raquel Portela, Nina Jeliazkova, Enrique Lozano, Bastian Barton and Iván Moya have received financial support from the EU H2020 project CHARISMA, GA n. 952921, Bojan Boskovic, Ennio Capria, Costas Charitidis, Donna Dykeman, Spyros Diplas, Gerhard Goldbeck, Marco Sebastiani, Elias Koumoulos, Silvia Giovanna Avataneo, Miguel A. Bañares, Raquel Portela, Anastasia Alexandratou, Athanasios Katsavrias, Fotis Mystakopoulos have received financial support from the EU H2020 project NanoMECommons, GA n. 952869, Nikolaj Zangernberg and Ennio Capria have received financial support from the EU H2020 project EASI-STRESS, GA n. 953219, Natalia Konchakova has received financial support from the EU H2020 project VIPCOAT, GA n. 952903, Costas Charitidis, Elias Koumoulos, and Spyros Diplas have received financial support from the EsSENce COST ACTION CA19118. All authors would like to specially acknowledge Anastasia Alexandratou, Athanasios Katsavrias and Fotis Mystakopoulos for their support in NMBP-35 joint Workshop organisation and documentation, and Steffen Neumann for his insights during the NMBP-35 joint Workshop discussions.Peer reviewe

MR

Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF+ or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community members even if they have not regularly participated in the programmes

Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune responses and reduced regulatory T cells

<div><p>Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4⁺ T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4⁺CD25^hiFoxp3⁺ regulatory T cells. These profiles included increased IL-17A⁺, IL-4⁺, RORC2⁺ and GATA3⁺CD4⁺ T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger <i>Onchocerca volvulus</i>-specific Th2 responses, especially IL-13, were observed <i>in vitro</i> in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis.</p></div