The Evolving Landscape of Flowcytometric Minimal Residual Disease Monitoring in B-Cell Precursor Acute Lymphoblastic Leukemia

Detection of minimal residual disease (MRD) is a major independent prognostic marker in the clinical management of pediatric and adult B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL), and risk stratification nowadays heavily relies on MRD diagnostics. MRD can be detected using flow cytometry based on aberrant expression of markers (antigens) during malignant B-cell maturation. Recent advances highlight the significance of novel markers (e.g., CD58, CD81, CD304, CD73, CD66c, and CD123), improving MRD identification. Second and next-generation flow cytometry, such as the EuroFlow consortium’s eight-color protocol, can achieve sensitivities down to 10−5 (comparable with the PCR-based method) if sufficient cells are acquired. The introduction of targeted therapies (especially those targeting CD19, such as blinatumomab or CAR-T19) introduces several challenges for flow cytometric MRD analysis, such as the occurrence of CD19-negative relapses. Therefore, innovative flow cytometry panels, including alternative B-cell markers (e.g., CD22 and CD24), have been designed. (Semi-)automated MRD assessment, employing machine learning algorithms and clustering tools, shows promise but does not yet allow robust and sensitive automated analysis of MRD. Future directions involve integrating artificial intelligence, further automation, and exploring multicolor spectral flow cytometry to standardize MRD assessment and enhance diagnostic and prognostic robustness of MRD diagnostics in BCP-ALL.</p

The Evolving Landscape of Flowcytometric Minimal Residual Disease Monitoring in B-Cell Precursor Acute Lymphoblastic Leukemia

Detection of minimal residual disease (MRD) is a major independent prognostic marker in the clinical management of pediatric and adult B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL), and risk stratification nowadays heavily relies on MRD diagnostics. MRD can be detected using flow cytometry based on aberrant expression of markers (antigens) during malignant B-cell maturation. Recent advances highlight the significance of novel markers (e.g., CD58, CD81, CD304, CD73, CD66c, and CD123), improving MRD identification. Second and next-generation flow cytometry, such as the EuroFlow consortium’s eight-color protocol, can achieve sensitivities down to 10−5 (comparable with the PCR-based method) if sufficient cells are acquired. The introduction of targeted therapies (especially those targeting CD19, such as blinatumomab or CAR-T19) introduces several challenges for flow cytometric MRD analysis, such as the occurrence of CD19-negative relapses. Therefore, innovative flow cytometry panels, including alternative B-cell markers (e.g., CD22 and CD24), have been designed. (Semi-)automated MRD assessment, employing machine learning algorithms and clustering tools, shows promise but does not yet allow robust and sensitive automated analysis of MRD. Future directions involve integrating artificial intelligence, further automation, and exploring multicolor spectral flow cytometry to standardize MRD assessment and enhance diagnostic and prognostic robustness of MRD diagnostics in BCP-ALL.</p

The response of wheat genotypes to inoculation with Azospirillum brasilense

It is well documented in many studies that plant growth promoting rhizobacteria (PGPR) are capable of increasing plant growth and productivity in a range of agricultural crops, reducing dependence on chemical amendments and maintaining a safe environment. Over the last two decades PGPR inoculants have been increasingly used in agriculture to improve crop productivity and farming system sustainability. Such eco-friendly technologies are needed to address sustainable food security and to avoid global dependence on hazardous agricultural chemicals which ultimately destabilize agro-ecosystems. The nitrogen fixing bacteria, Azospirillum brasilense, has been an important PGPB (plant growth promoting bacteria) used to enhance the growth and yield of many crops globally. This is attributed mainly to its ability to produce phytohormones. While much is known about A. brasilense, the promising effect of PGPBs in general in the field is limited by factors that influence their survival and activity in the rhizosphere. The attachment of bacteria to roots is an essential and necessary condition for the establishment of an effective association. This association is dependent upon the population density of active PGPB cells in the rhizosphere which are able to compete with indigenous bacteria. However, how survival and persistence of inoculant bacteria in the rhizosphere, the effect of inoculum on the rhizosphere community, in particular the nitrogen fixing community, and the effect of plant genotype contributes to plant growth promotion by Azospirillum in the field have not been widely studied. Better understanding of the plant x inoculum interaction requires determining if there is an effect of plant genotype and monitoring and estimation of the persistence of PGPB in the rhizosphere. The overall aim of this project was to examine the effect of the wheat (Triticum aestivum) genotype x Azospirillum interaction on colonization of roots and plant growth promotion. These effects were studied under both controlled hydroponic conditions in the laboratory and in the field. Plant growth parameters and bacterial colonization of the rhizosphere were determined in both conditions. Differences in root characteristics of twenty three diverse wheat genotypes were observed after growth in the hydroponic system; however responses to inoculation with A. brasilense Sp7 and Sp7-S were variable. In some cases growth parameters were increased and in others they were decreased. There was an apparent increase in responsiveness to inoculation with azospirilla by synthetically derived genotypes observed in root length measurements but otherwise there was no trend according to the genetic source of wheat. Microscopic observations confirmed the different root colonisation patterns by Sp7 and Sp7-S. However, colonisation pattern was not influenced by plant genotype. Relationships between shoot dry weight and root growth parameters were positive as expected but were strengthened with inoculation

On Negotiation as Concurrency Primitive

We introduce negotiations, a model of concurrency close to Petri nets, with multiparty negotiation as primitive. We study the problems of soundness of negotiations and of, given a negotiation with possibly many steps, computing a summary, i.e., an equivalent one-step negotiation. We provide a complete set of reduction rules for sound, acyclic, weakly deterministic negotiations and show that, for deterministic negotiations, the rules compute the summary in polynomial time

Identification of common carp innate immune genes with whole-genome sequencing and RNA-seq data

169Computer Systems, Imagery and MediaAnimal science

Large-scale zero-shot learning in the wild: classifying zoological illustrations

In this paper we analyse the classification of zoological illustrations. Historically, zoological illustrations were the modus operandi for the documentation of new species, and now serve as crucial sources for long-term ecological and biodiversity research. By employing computational methods for classification, the data can be made amenable to research. Automated species identification is challenging due to the long-tailed nature of the data, and the millions of possible classes in the species taxonomy. Success commonly depends on large training sets with many examples per class, but images from only a subset of classes are digitally available, and many images are unlabelled, since labelling requires domain expertise. We explore zero-shot learning to address the problem, where features are learned from classes with medium to large samples, which are then transferred to recognise classes with few or no training samples. We specifically explore how distributed, multi-modal background knowledge from data providers, such as the Global Biodiversity Information Facility (GBIF), iNaturalist, and the Biodiversity Heritage Library (BHL), can be used to share knowledge between classes for zero-shot learning. We train a prototypical network for zero-shot classification, and introduce fused prototypes (FP) and hierarchical prototype loss (HPL) to optimise the model. Finally, we analyse the performance of the model for use in real-world applications. The experimental results are encouraging, indicating potential for use of such models in an expert support system, but also express the difficulty of our task, showing a necessity for research into computer vision methods that are able to learn from small samples.Computer Systems, Imagery and Medi

A clinical decision aid to discern patients without and with midfacial and mandibular fractures that require treatment (the REDUCTION-II study):a prospective multicentre cohort study

Purpose: To assess the diagnostic accuracy of physical examination findings and to construct clinical decision aids to discern emergency department patients without and with midfacial and mandibular fractures that require treatment. Methods: A prospective multicentre cohort study was conducted in four hospitals in the Netherlands. Consecutive maxillofacial trauma patients were included whereupon each patient underwent a standardized physical examination consisting of 15 and 14 findings for midfacial and mandibular trauma, respectively. The primary outcome was the decision whether to treat during the emergency department stay or within 24 h of admission. The diagnostic accuracy was calculated for the individual physical examination findings and ensuing clinical decision aids with the focus being on detecting midfacial and mandibular fractures that require active treatment. Results: A total of 766 midfacial trauma patients were identified of whom 339 (44.3%) had midfacial fractures. Of those, 74 (21.8%) required active treatment. A total of 280 mandibular trauma patients were identified of whom 66 (23.6%) had mandibular fractures. Of those, 37 (56.0%) required active treatment. The decision aid for midfacial trauma consisting of facial depression, epistaxis, ocular movement limitation, palpable step-off, objective malocclusion and tooth mobility or avulsion had a sensitivity of 97.3 (90.7–99.3), a specificity of 38.6 (35.0–42.3), and a negative predictive value of 99.3 (97.3–99.8). The decision aid for mandibular trauma consisting of mouth opening limitation, jaw movement pain, objective malocclusion and tooth mobility or avulsion resulted in a sensitivity of 100.0 (90.6–100.0), a specificity of 39.1 (33.2–45.4), and a negative predictive value of 100.0 (96.1–100.0). Conclusion: The clinical decision aids successfully identified midfacial and mandibular trauma patients requiring active fracture treatment and so may be useful in preventing unnecessary radiological procedures in the future. Trial Registration: The study was registered at ClinicalTrials.gov with the identifier NCT03314480

Semantic annotation of natural history collections

Large collections of historical biodiversity expeditions are housed in natural history museums throughout the world. Potentially they can serve as rich sources of data for cultural historical and biodiversity research. However, they exist as only partially catalogued specimen repositories and images of unstructured, non-standardised, hand-written text and drawings. Although many archival collections have been digitised, disclosing their content is challenging. They refer to historical place names and outdated taxonomic classifications and are written in multiple languages. Efforts to transcribe the hand-written text can make the content accessible, but semantically describing and interlinking the content would further facilitate research. We propose a semantic model that serves to structure the named entities in natural history archival collections. In addition, we present an approach for the semantic annotation of these collections whilst documenting their provenance. This approach serves as an initial step for an adaptive learning approach for semi-automated extraction of named entities from natural history archival collections. The applicability of the semantic model and the annotation approach is demonstrated using image scans from a collection of 8, 000 field book pages gathered by the Committee for Natural History of the Netherlands Indies between 1820 and 1850, and evaluated together with domain experts from the field of natural and cultural history.Computer Systems, Imagery and Medi

Minimal residual disease assessment in B-cell precursor acute lymphoblastic leukemia by semi-automated identification of normal hematopoietic cells:A EuroFlow study

Presence of minimal residual disease (MRD), detected by flow cytometry, is an important prognostic biomarker in the management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, data-analysis remains mainly expert-dependent. In this study, we designed and validated an Automated Gating &amp; Identification (AGI) tool for MRD analysis in BCP-ALL patients using the two tubes of the EuroFlow 8-color MRD panel. The accuracy, repeatability, and reproducibility of the AGI tool was validated in a multicenter study using bone marrow follow-up samples from 174 BCP-ALL patients, stained with the EuroFlow BCP-ALL MRD panel. In these patients, MRD was assessed both by manual analysis and by AGI tool supported analysis. Comparison of MRD levels obtained between both approaches showed a concordance rate of 83%, with comparable concordances between MRD tubes (tube 1, 2 or both), treatment received (chemotherapy versus targeted therapy) and flow cytometers (FACSCanto versus FACSLyric). After review of discordant cases by additional experts, the concordance increased to 97%. Furthermore, the AGI tool showed excellent intra-expert concordance (100%) and good inter-expert concordance (90%). In addition to MRD levels, also percentages of normal cell populations showed excellent concordance between manual and AGI tool analysis. We conclude that the AGI tool may facilitate MRD analysis using the EuroFlow BCP-ALL MRD protocol and will contribute to a more standardized and objective MRD assessment. However, appropriate training is required for the correct analysis of MRD data.</p