BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a heterogenous autoimmune disease. While traditionally stratified into two conditions, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the subclassification of ANCA-associated vasculitis is subject to continued debate. Here we aim to identify phenotypically distinct subgroups and develop a data-driven subclassification of ANCA-associated vasculitis, using a large real-world dataset. METHODS: In the collaborative data reuse project FAIRVASC (Findable, Accessible, Interoperable, Reusable, Vasculitis), registry records of patients with ANCA-associated vasculitis were retrieved from six European vasculitis registries: the Czech Registry of ANCA-associated vasculitis (Czech Republic), the French Vasculitis Study Group Registry (FVSG; France), the Joint Vasculitis Registry in German-speaking Countries (GeVas; Germany), the Polish Vasculitis Registry (POLVAS; Poland), the Irish Rare Kidney Disease Registry (RKD; Ireland), and the Skåne Vasculitis Cohort (Sweden). We performed model-based clustering of 17 mixed-type clinical variables using a parsimonious mixture of two latent Gaussian variable models. Clinical validation of the optimal cluster solution was made through summary statistics of the clusters' demography, phenotypic and serological characteristics, and outcome. The predictive value of models featuring the cluster affiliations were compared with classifications based on clinical diagnosis and ANCA specificity. People with lived experience were involved throughout the FAIRVASVC project. FINDINGS: A total of 3868 patients diagnosed with ANCA-associated vasculitis between Nov 1, 1966, and March 1, 2023, were included in the study across the six registries (Czech Registry n=371, FVSG n=1780, GeVas n=135, POLVAS n=792, RKD n=439, and Skåne Vasculitis Cohort n=351). There were 2434 (62·9%) patients with GPA and 1434 (37·1%) with MPA. Mean age at diagnosis was 57·2 years (SD 16·4); 2006 (51·9%) of 3867 patients were men and 1861 (48·1%) were women. We identified five clusters, with distinct phenotype, biochemical presentation, and disease outcome. Three clusters were characterised by kidney involvement: one severe kidney cluster (555 [14·3%] of 3868 patients) with high C-reactive protein (CRP) and serum creatinine concentrations, and variable ANCA specificity (SK cluster); one myeloperoxidase (MPO)-ANCA-positive kidney involvement cluster (782 [20·2%]) with limited extrarenal disease (MPO-K cluster); and one proteinase 3 (PR3)-ANCA-positive kidney involvement cluster (683 [17·7%]) with widespread extrarenal disease (PR3-K cluster). Two clusters were characterised by relative absence of kidney involvement: one was a predominantly PR3-ANCA-positive cluster (1202 [31·1%]) with inflammatory multisystem disease (IMS cluster), and one was a cluster (646 [16·7%]) with predominantly ear-nose-throat involvement and low CRP, with mainly younger patients (YR cluster). Compared with models fitted with clinical diagnosis or ANCA status, cluster-assigned models demonstrated improved predictive power with respect to both patient and kidney survival. INTERPRETATION: Our study reinforces the view that ANCA-associated vasculitis is not merely a binary construct. Data-driven subclassification of ANCA-associated vasculitis exhibits higher predictive value than current approaches for key outcomes. FUNDING: European Union's Horizon 2020 research and innovation programme under the European Joint Programme on Rare Diseases.
- MeSH
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * classification diagnosis epidemiology blood immunology MeSH
- Adult MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Microscopic Polyangiitis classification epidemiology blood diagnosis immunology MeSH
- Registries * statistics & numerical data MeSH
- Aged MeSH
- Cluster Analysis MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
A novel endophytic fungus producing beta-glucosidase was isolated and characterized from pigeon pea (Cajanus cajan [L.] Millsp.), which has excellent properties in converting ginsenoside Rb1 to ginsenoside Rd in Panax notoginseng. According to the 16S rDNA gene sequence, the G11-7 strain was identified as Fusarium proliferatum, and the accession number KY303906 was confirmed in GenBank. The G11-7 immobilized spores, in which the activity of beta-glucosidase could reach 0.95 U/mL, were co-cultured with P. notoginseng plant material to obtain a continuous beta-glucosidase supply for the biotransformation of ginsenoside Rb1 to Rd. Under the liquid-solid ratio (20:1), initial pH (6.0), and temperature (30 °C) constituents, the maximum ginsenoside Rd yield was obtained as 9.15 ± 0.65 mg/g, which was 3.67-fold higher than that without fungal spore co-culture (2.49 ± 0.98 mg/g). Furthermore, immobilized G11-7 spores showed significant beta-glucosidase producing ability which could be recovered and reused for 6 cycles. Overall, these results suggested that immobilized G11-7 offered a promising and effective approach to enhance the production of ginsenoside Rd for possible nutraceutical and pharmaceutical uses.
The consequence of the massive increase in population in recent years is the enormous production of mainly industrial waste. The effort to minimize these waste products is, therefore, no longer sufficient. Biotechnologists, therefore, started looking for ways to not only reuse these waste products, but also to valorise them. This work focuses on the biotechnological use and processing of waste oils/fats and waste glycerol by carotenogenic yeasts of the genus Rhodotorula and Sporidiobolus. The results of this work show that the selected yeast strains are able to process waste glycerol as well as some oils and fats in a circular economy model and, moreover, are resistant to potential antimicrobial compounds present in the medium. The best-growing strains, Rhodotorula toruloides CCY 062-002-004 and Rhodotorula kratochvilovae CCY 020-002-026, were selected for fed-batch cultivation in a laboratory bioreactor in a medium containing a mixture of coffee oil and waste glycerol. The results show that both strains were able to produce more than 18 g of biomass per litre of media with a high content of carotenoids (10.757 ± 1.007 mg/g of CDW in R. kratochvilovae and 10.514 ± 1.520 mg/g of CDW in R. toruloides, respectively). The overall results prove that combining different waste substrates is a promising option for producing yeast biomass enriched with carotenoids, lipids, and beta-glucans.
- Publication type
- Journal Article MeSH
The diagnosis of solid tumors of epithelial origin (carcinomas) represents a major part of the workload in clinical histopathology. Carcinomas consist of malignant epithelial cells arranged in more or less cohesive clusters of variable size and shape, together with stromal cells, extracellular matrix, and blood vessels. Distinguishing stroma from epithelium is a critical component of artificial intelligence (AI) methods developed to detect and analyze carcinomas. In this paper, we propose a novel automated workflow that enables large-scale guidance of AI methods to identify the epithelial component. The workflow is based on re-staining existing hematoxylin and eosin (H&E) formalin-fixed paraffin-embedded sections by immunohistochemistry for cytokeratins, cytoskeletal components specific to epithelial cells. Compared to existing methods, clinically available H&E sections are reused and no additional material, such as consecutive slides, is needed. We developed a simple and reliable method for automatic alignment to generate masks denoting cytokeratin-rich regions, using cell nuclei positions that are visible in both the original and the re-stained slide. The registration method has been compared to state-of-the-art methods for alignment of consecutive slides and shows that, despite being simpler, it provides similar accuracy and is more robust. We also demonstrate how the automatically generated masks can be used to train modern AI image segmentation based on U-Net, resulting in reliable detection of epithelial regions in previously unseen H&E slides. Through training on real-world material available in clinical laboratories, this approach therefore has widespread applications toward achieving AI-assisted tumor assessment directly from scanned H&E sections. In addition, the re-staining method will facilitate additional automated quantitative studies of tumor cell and stromal cell phenotypes.
Ticks are blood-feeding ectoparasites with distinct genomic reductions, inevitably linking them to a parasitic lifestyle. Ticks have lost the genomic coding and, thus, biochemical capacity to synthesize heme, an essential metabolic cofactor, de novo. Instead, they are equipped with acquisition and distribution pathways for reuse of host heme. Unlike insects or mammals, ticks and mites cannot cleave the porphyrin ring of heme to release iron. Bioavailable iron is thus acquired by ticks from the host serum transferrin. Somatic trafficking of iron, however, is independent of heme and is mediated by a secretory type of ferritin. Heme and iron systemic homeostasis in ticks represents, therefore, key adaptive traits enabling successful feeding and reproduction.
- MeSH
- Heme metabolism MeSH
- Homeostasis MeSH
- Ticks * MeSH
- Mites * MeSH
- Mammals MeSH
- Iron metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The current pandemic resulted in a rapidly increasing demand for personal protective equipment (PPE) initially leading to severe shortages of these items. Hence, during an unexpected and fast virus spread, the possibility of reusing highly efficient protective equipment could provide a viable solution for keeping both healthcare professionals and the general public equipped and protected. This requires an efficient decontamination technique that preserves functionality of the sensitive materials used for PPE production. Non-thermal plasma (NTP) is a decontamination technique with documented efficiency against select bacterial and fungal pathogens combined with low damage to exposed materials. We have investigated NTP for decontamination of high-efficiency P3 R filters from viral respiratory pathogens in comparison to other commonly used techniques. We show that NTP treatment completely inactivates SARS-CoV-2 and three other common human respiratory viruses including Influenza A, Rhinovirus and Adenovirus, revealing an efficiency comparable to 90°C dry heat or UVC light. Unlike some of the tested techniques (e.g., autoclaving), NTP neither influenced the filtering efficiency nor the microstructure of the filter. We demonstrate that NTP is a powerful and economic technology for efficient decontamination of protective filters and other sensitive materials from different respiratory pathogens.
- Publication type
- Journal Article MeSH
Despite several efforts to unravel the microbial diversity of soil, most microbes are still unknown. A recent large-scale effort based on genome-resolved metagenomics by Nayfach et al. has demonstrated how this approach can expand our understanding of novel bacterial lineages, including those from soils. Genomic catalogs of soil microbiomes are now enabling a deeper investigation of the evolutionary and functional role of high-complex soil microbiomes, promoting new knowledge from the reuse and sharing of multi-omics data.
- MeSH
- Bacteria genetics MeSH
- Genetic Variation * MeSH
- Genome, Bacterial * MeSH
- Metagenomics methods MeSH
- Soil Microbiology * MeSH
- Publication type
- Journal Article MeSH
Fenton processes are promising wastewater treatment alternatives for bio-recalcitrant compounds. Three different methods (i.e., reverse microemulsion, sol-gel, and combustion) were designed to synthesize environmentally friendly ferrites as magnetically recoverable catalysts to be applied for the decomposition of two pharmaceuticals (ciprofloxacin and carbamazepine) that are frequently detected in water bodies. The catalysts were used in a heterogeneous solar photo-Fenton treatment to save the cost of applying high-energy UV radiation sources, and was performed under a slightly basic pH to avoid metal leaching and adding salts for pH adjustment. All the developed catalysts resulted in the effective treatment of ciprofloxacin and carbamazepine in both synthetic and real domestic wastewater. In particular, the sol-gel synthesized ferrite was more magnetic and more suitable for reuse. The degradation pathways of both compounds were elucidated for this treatment. The degradation of ciprofloxacin involved attacks to the quinolone and piperazine rings. The degradation pathway of carbamazepine involved the formation of hydroxyl carbamazepine and dihydroxy carbamazepine before yielding acridine by hydrogen abstraction, decarboxylation, and amine cleavage, which would be further oxidized.
- MeSH
- Anti-Bacterial Agents chemistry MeSH
- Water Pollutants, Chemical chemistry MeSH
- Ciprofloxacin chemistry MeSH
- Carbamazepine chemistry MeSH
- Catalysis MeSH
- Magnetic Phenomena MeSH
- Waste Disposal, Fluid methods MeSH
- Wastewater MeSH
- Sunlight MeSH
- Ferric Compounds chemistry radiation effects MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Phosphorus reuse by application of biochar is a recent concept that needs to be supported by long-term field data. To monitor biochar's long-term effects on P turnover, one-off biochar was applied in 2013 with mineral NPK fertilizers being applied every year since then. Biochar application rates included 0 t ha-1 (CK), 15.75 t ha-1 (BC1), 31.5 t ha-1 (BC2), and 47.25 t ha-1 (BC3). Over the 5 years' field experiment, P distribution in soil profile, inorganic and organic P fractions in bulk, and rhizosphere soil and maize P uptake were determined. The results showed that biochar reduced the inorganic P fractions (Ca2-P, Ca8-P, Al-P, Fe-P and O-P by 4.8-33.7%, 8.8-59.0%, 13.7-28.6%, 8.4-17.6%, and 3.3-25.5%, respectively), and increased organic P fractions (MLOP and HROP by 67.2-11.6% and 18.8-87.7%, respectively) in bulk soil, while in rhizosphere soil, Fe-P and MLOP were decreased by 13.4-34.5% and 67.2-111.6%, respectively, in 2017. After the application of biochar for 5 years, moderately labile organic phosphorus (MLOP), moderately resistant organic phosphorus (MROP), and highly resistant organic phosphorus (HROP) with different biochar treatments were enhanced by 12.8-42.7%, 20.1-48.0%, and 5.5-66.6%, respectively, but Ca8-P, Al-P, O-P, and Ca10-P were all decreased by 18.6-24.9%, 16.4-21.4%, and 3.3-23.48%, respectively. Total P storage in 0-100 cm was declined by biochar. Increases in maize P uptake in the stover (38.6-71.3%) and grain (20.9-25.5%) were occurred after 31.5 t ha-1 and 47.25 t ha-1 biochar addition. To sum up, biochar is found to regulate the distribution, storage, and transformation of soil P, which lead to increase in maize P uptake.
- MeSH
- Charcoal MeSH
- Phosphorus * MeSH
- Zea mays MeSH
- Fertilizers analysis MeSH
- Soil * MeSH
- Publication type
- Journal Article MeSH
The occurrence of chemical and biological contaminants of emerging concern (CECs) was investigated in treated wastewater intended for reuse in agriculture. An agarose hydrogel diffusion-based passive sampler was exposed to the outlet of a wastewater treatment plant (WWTP) located in Cyprus, which is equipped with membrane bioreactor (MBR). Passive samplers in triplicate were exposed according to a time-series exposure plan with maximum exposure duration of 28 days. Composite flow-proportional wastewater samples were collected in parallel with the passive sampling exposure plan and were processed by solid phase extraction using HORIZON SPE-DEX 4790 and the same sorbent material (Oasis HLB) as in the passive sampler. The analysis of passive samplers and wastewater samples enabled (i) the field-scale calibration of the passive sampler prototype by the calculation of in situ sampling rates of target substances, and (ii) the investigation of in silico predicted transformation products of the four most ecotoxicologically hazardous antibiotics (azithromycin, clarithromycin, erythromycin, ofloxacin). Additionally, the wastewater samples were subjected to the analysis of seven preselected antibiotic resistant genes (ARGs) and one mobile resistant element (int1). All extracts were analyzed for chemicals in a single batch using a highly sensitive method for pharmaceuticals, antibiotics and illicit drugs by liquid chromatography tandem MS/MS (LC-QQQ) and for various other target compounds (2316 compounds in total) by liquid chromatography high-resolution mass spectrometry (LC-HRMS). 279 CECs and all investigated ARGs (except for blaCTX-M-32) were detected, highlighting potential chemical and biological hazards related to wastewater reuse practices. 16 CECs were prioritized following ecotoxicological risk assessment, whereas sul1 and the mobile resistant element (int1) showed the highest abundance. Comprehensive monitoring efforts using novel sampling methods such as passive sampling, wide-scope target screening and molecular analysis are required to assure safe application of wastewater reuse and avoid spread and crop uptake of potentially hazardous chemicals.
