Detection of HER2 from Haematoxylin-Eosin Slides Through a Cascade of Deep Learning Classifiers via Multi-Instance Learning

Breast cancer is the most frequently diagnosed cancer in woman. The correct identification of the HER2 receptor is a matter of major importance when dealing with breast cancer: an over-expression of HER2 is associated with aggressive clinical behaviour; moreover, HER2 targeted therapy results in a significant improvement in the overall survival rate. In this work, we employ a pipeline based on a cascade of deep neural network classifiers and multi-instance learning to detect the presence of HER2 from Haematoxylin–Eosin slides, which partly mimics the pathologist’s behaviour by first recognizing cancer and then evaluating HER2. Our results show that the proposed system presents a good overall effectiveness. Furthermore, the system design is prone to further improvements that can be easily deployed in order to increase the effectiveness score.Eduardo Conde-Sousa was supported by the project PPBI-POCI-01-0145-FEDER-022122, in the scope of Fundação para a Ciência e Tecnologia, Portugal (FCT) National Roadmap of Research Infrastructures

Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer hematològic; Malalties infecciosesCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cáncer hematológico; Enfermedades infecciosasCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Haematological cancer; Infectious diseasesCOVID-19 is posing a significant threat to health in vulnerable patients, such as immunocompromised patients. For hematopoietic cell transplantation (HCT) recipients and patients with hematologic malignancies it is known that COVID-19 leads to severe morbidity and high mortality as compared to the general population [1–3]. For patients treated with Chimeric Antigen Receptor T-cell (CAR-T-cell) therapy for B-cell malignancies however, descriptions of the clinical course and outcome are still limited to small case series and case reports [4–8]. CAR-T-cell therapy recipients are believed to be at high risk of poor outcomes from COVID-19 due to their severely immunocompromised state, caused by prior lymphodepleting immunochemotherapy and CAR-T-cell therapy related side effects such as B-cell depletion, hypogammaglobulinemia, and cytopenias. In order to rapidly inform the medical field on the impact of COVID-19 on CAR-T-cell therapy recipients, the EBMT Infectious Diseases Working Party and the EHA Lymphoma Group joined forces and present the clinical course of COVID-19 in the largest European cohort to date

HEROHE Challenge: Predicting HER2 Status in Breast Cancer from Hematoxylin–Eosin Whole-Slide Imaging

Breast cancer is the most common malignancy in women worldwide, and is responsible for more than half a million deaths each year. The appropriate therapy depends on the evaluation of the expression of various biomarkers, such as the human epidermal growth factor receptor 2 (HER2) transmembrane protein, through specialized techniques, such as immunohistochemistry or in situ hybridization. In this work, we present the HER2 on hematoxylin and eosin (HEROHE) challenge, a parallel event of the 16th European Congress on Digital Pathology, which aimed to predict the HER2 status in breast cancer based only on hematoxylin–eosin-stained tissue samples, thus avoiding specialized techniques. The challenge consisted of a large, annotated, whole-slide images dataset (509), specifically collected for the challenge. Models for predicting HER2 status were presented by 21 teams worldwide. The best-performing models are presented by detailing the network architectures and key parameters. Methods are compared and approaches, core methodologies, and software choices contrasted. Different evaluation metrics are discussed, as well as the performance of the presented models for each of these metrics. Potential differences in ranking that would result from different choices of evaluation metrics highlight the need for careful consideration at the time of their selection, as the results show that some metrics may misrepresent the true potential of a model to solve the problem for which it was developed. The HEROHE dataset remains publicly available to promote advances in the field of computational pathology

A Case of Tuberculosis Cutis Colliquativa Treated with Rifampicin and Isoniazid

non

A mixed methods approach to urban ecosystem services: experienced environmental quality and its role in ecosystem assessment within an inner-city estate

This paper contributes to the notion of ecosystem services (ES) and dis-services (EDS) through an exploration of how they are experienced in an inner-city neighbourhood. We contrast the findings of a science-led assessment with qualitative interview and visual data from the residents of the Woodberry Down Estate (London, UK). We use the ontology of co-production and co-construction to understand how material and interpretative factors condition the translation of identified service-providing units (SPUs) into directly experienced ES and EDS. Findings demonstrate that aspects contributing to the perceived liveability of a neighbourhood also condition the experienced ES and EDS. In our case study, the history of the estate translates into subjective feelings of safety which influence whether individuals access parts of the regenerated estate. While the regeneration project provides a broad range of new and improved SPUs with significant ES potential, the access and recreational functions these offer are especially appreciated for the increased opportunities for social interaction and visitors they provide. However, new SPUs such as landscape vistas and formal gardens that attract people are also assigned further significance as markers of new divisions among social housing residents. We suggest that in order to realise the much-prophesised health and wellbeing benefits of urban ES in an equitable manner, a science-led approach to designing and assessing potential ES should be accompanied by a context-sensitive assessment of community needs and liveability aspects

Does bathymetry drive coastal whale shark (Rhincodon typus) aggregations?

Background The whale shark (Rhincodon typus) is known to aggregate in a number of coastal locations globally, however what causes these aggregations to form where they do is largely unknown. This study examines whether bathymetry is an important driver of coastal aggregation locations for R. typus through bathymetry’s effect on primary productivity and prey availability. This is a global study taking into account all coastal areas within R. typus’ range. Methods R. typus aggregation locations were identified through an extensive literature review. Global bathymetric data were compared at R. typus aggregation locations and a large random selection of non-aggregation areas. Generalised linear models were used to assess which bathymetric characteristic had the biggest influence on aggregation presence. Results Aggregation sites were significantly shallower than non-aggregation sites and in closer proximity to deep water (the mesopelagic zone) by two orders of magnitude. Slope at aggregation sites was significantly steeper than non-aggregation sites. These three bathymetric variables were shown to have the biggest association with aggregation sites, with up to 88% of deviation explained by the GLMs. Discussion The three key bathymetric characteristics similar at the aggregation sites are known to induce upwelling events, increase primary productivity and consequently attract numerous other filter feeding species. The location of aggregation sites in these key areas can be attributed to this increased prey availability, thought to be the main reason R. typus aggregations occur, extensively outlined in the literature. The proximity of aggregations to shallow areas such as reefs could also be an important factor why whale sharks thermoregulate after deep dives to feed. These findings increase our understanding of whale shark behaviour and may help guide the identification and conservation of further aggregation sites

Winning Fights Induces Hyperaggression via the Action of the Biogenic Amine Octopamine in Crickets

Winning an agonistic interaction against a conspecific is known to heighten aggressiveness, but the underlying events and mechanism are poorly understood. We quantified the effect of experiencing successive wins on aggression in adult male crickets (Gryllus bimaculatus) by staging knockout tournaments and investigated its dependence on biogenic amines by treatment with amine receptor antagonists. For an inter-fight interval of 5 min, fights between winners escalated to higher levels of aggression and lasted significantly longer than the preceding round. This winner effect is transient, and no longer evident for an inter-fight interval of 20 min, indicating that it does not result from selecting individuals that were hyper-aggressive from the outset. A winner effect was also evident in crickets that experienced wins without physical exertion, or that engaged in fights that were interrupted before a win was experienced. Finally, the winner effect was abolished by prior treatment with epinastine, a highly selective octopamine receptor blocker, but not by propranolol, a ß-adrenergic receptor antagonist, nor by yohimbine, an insect tyramine receptor blocker nor by fluphenazine an insect dopamine-receptor blocker. Taken together our study in the cricket indicates that the physical exertion of fighting, together with some rewarding aspect of the actual winning experience, leads to a transient increase in aggressive motivation via activation of the octopaminergic system, the invertebrate equivalent to the adrenergic system of vertebrates

Combating resistance while maintaining innovation: the future of antimicrobial stewardship

Antimicrobial resistance represents a significant global health threat. However, a commercial model that does not offer a return on investment resulting in a lack of investment in antibiotic R&D, means that the current pipeline of antibiotics lacks sufficient innovation to meet this challenge. Those responsible for defining, promoting and monitoring the rationale use of antibiotics (the antimicrobial stewardship programme) are key to addressing current shortcomings. In this personal perspective, we discuss the future role stewardship can play in stimulating innovation, a need to move away from a pharmacy budget dominated view of antibiotic use, and the impact of the ever-increasing sophistication and interdisciplinary nature of antimicrobial control programs. Changes are needed to optimize clinical outcomes for patients

Explaining the rank order of invasive plants by stakeholder groups

Debates surrounding the use of policies to avoid further spread of invasive species highlight the need to establish priorities in public resource allocations. We explore the consistency or discrepancy among stakeholder groups involved in the risk and control management of invasive species to identify the extent to which different factors influence stakeholder choices of major relevant plant invaders. Based on stakeholder ranking of invasive plants, we explore the reasons behind stakeholders' support for policy management. Data were collected in Galicia, Spain, where a catalogue of prohibited entry and trade of invasive species is currently under debate. We estimate a rank ordered logit model using information from semi-structured interviews conducted with respondents from four stakeholder groups: public administration sector, ornamental sector, research and social groups. The characteristics of plant invaders that provoke stakeholders to rank a species more highly are wide distribution of plant invaders, existence of public control programmes, use and sale of species in the ornamental sector and media coverage. The influence these aspects have in the selection of top-ranked invaders varies across different stakeholder groups and with stakeholders' level of knowledge, awareness and attitudes towards different potential policy measures. A small group of invaders are perceived as top rated by all stakeholder groups