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

Neotectonics of the Sea of Galilee (northeast Israel): implication for geodynamics and seismicity along the Dead Sea Fault system

The Sea of Galilee in northeast Israel is a freshwater lake filling a morphological depression along the Dead Sea Fault. It is located in a tectonically complex area, where a N-S main fault system intersects secondary fault patterns non-univocally interpreted by previous reconstructions. A set of multiscale geophysical, geochemical and seismological data, reprocessed or newly collected, was analysed to unravel the interplay between shallow tectonic deformations and geodynamic processes. The result is a neotectonic map highlighting major seismogenic faults in a key region at the boundary between the Africa/Sinai and Arabian plates. Most active seismogenic displacement occurs along NNW-SSE oriented transtensional faults. This results in a left-lateral bifurcation of the Dead Sea Fault forming a rhomb-shaped depression we named the Capharnaum Trough, located off-track relative to the alleged principal deformation zone. Low-magnitude (ML = 3–4) epicentres accurately located during a recent seismic sequence are aligned along this feature, whose activity, depth and regional importance is supported by geophysical and geochemical evidence. This case study, involving a multiscale/multidisciplinary approach, may serve as a reference for similar geodynamic settings in the world, where unravelling geometric and kinematic complexities is challenging but fundamental for reliable earthquake hazard assessments

Best Practice Recommendations for the Implementation of a Digital Pathology Workflow in the Anatomic Pathology Laboratory by the European Society of Digital and Integrative Pathology (ESDIP)

The interest in implementing digital pathology (DP) workflows to obtain whole slide image (WSI) files for diagnostic purposes has increased in the last few years. The increasing performance of technical components and the Food and Drug Administration (FDA) approval of systems for primary diagnosis led to increased interest in applying DP workflows. However, despite this revolutionary transition, real world data suggest that a fully digital approach to the histological workflow has been implemented in only a minority of pathology laboratories. The objective of this study is to facilitate the implementation of DP workflows in pathology laboratories, helping those involved in this process of transformation to identify: (a) the scope and the boundaries of the DP transformation; (b) how to introduce automation to reduce errors; (c) how to introduce appropriate quality control to guarantee the safety of the process and (d) the hardware and software needed to implement DP systems inside the pathology laboratory. The European Society of Digital and Integrative Pathology (ESDIP) provided consensus-based recommendations developed through discussion among members of the Scientific Committee. The recommendations are thus based on the expertise of the panel members and on the agreement obtained after virtual meetings. Prior to publication, the recommendations were reviewed by members of the ESDIP Board. The recommendations comprehensively cover every step of the implementation of the digital workflow in the anatomic pathology department, emphasizing the importance of interoperability, automation and tracking of the entire process before the introduction of a scanning facility. Compared to the available national and international guidelines, the present document represents a practical, handy reference for the correct implementation of the digital workflow in Europe.publishedVersio

The Bortoluzzi Mud Volcano (Ionian Sea, Italy) and its potential for tracking the seismic cycle of active faults

The Ionian Sea in southern Italy is at the center of active interaction and convergence between the Eurasian and African–Adriatic plates in the Mediterranean. This area is seismically active with instrumentally and/or historically recorded Mw > 7:0 earthquakes, and it is affected by recently discovered long strike-slip faults across the active Calabrian accretionary wedge. Many mud volcanoes occur on top of the wedge. A recently discovered one (called the Bortoluzzi Mud Volcano or BMV) was surveyed during the Seismofaults 2017 cruise (May 2017). Bathymetric backscatter surveys, seismic reflection profiles, geochemical and earthquake data, and a gravity core are used here to geologically, geochemically, and geophysically characterize this structure. The BMV is a circular feature ' 22m high and ' 1100m in diameter with steep slopes (up to a dip of 22 ). It sits atop the Calabrian accretionary wedge and a system of flowerlike oblique-slip faults that are probably seismically active as demonstrated by earthquake hypocentral and focal data. Geochemistry of water samples from the seawater column on top of the BMV shows a significant contamination of the bottom waters from saline (evaporite-type) CH4-dominated crustalderived fluids similar to the fluids collected from a mud volcano located on the Calabria mainland over the same accretionary wedge. These results attest to the occurrence of open crustal pathways for fluids through the BMV down to at least the Messinian evaporites at about 3000 m. This evidence is also substantiated by helium isotope ratios and by comparison and contrast with different geochemical data from three seawater columns located over other active faults in the Ionian Sea area. One conclusion is that the BMV may be useful for tracking the seismic cycle of active faults through geochemical monitoring. Due to the widespread diffusion of mud volcanoes in seismically active settings, this study contributes to indicating a future path for the use of mud volcanoes in the monitoring and mitigation of natural hazards.Published1-233SR TERREMOTI - Attività dei CentriJCR Journa

CAJA 27 - LEGAJO II - SIGNATURA 2

Memorial de Polonia Eres, Viuda de D. Vicente Coma, Ofreciendo a la Sociedad las máquinas de su esposo a cambio de alguna gratificación. Informe sobre lo mismo.Eres, P.; Comandasi, A. (1797). Memorial de Polonia Eres, Viuda de D. Vicente Coma, Ofreciendo a la Sociedad las máquinas de su esposo a cambio de alguna gratificación. Informe sobre lo mismo. Real Sociedad Económica de Amigos del País de Valencia. http://hdl.handle.net/10251/19344Importación Masiv

The Thomsen-Friedenreich Antigen: A Highly Sensitive and Specific Predictor of Microsatellite Instability in Gastric Cancer

Microsatellite instability (MSI) is a distinct molecular subtype of gastric cancer. In recent years, the clinical consequences of MSI and the therapeutic opportunities to target this peculiar cancer subtype became evident. However, despite the importance of MSI for the stratification of patients, the time and resources required for diagnosis still present an obstacle. In an attempt to identify a new marker for MSI in gastric cancer, we evaluated the expression of five cancer-associated glycan epitopes in a cohort of 13 MSI and 17 microsatellite stable (MSS) cases. Our analysis revealed a highly significant (p < 0.001) association between the expression of the Thomsen-Friedenreich (TF) antigen and MSI status. Hence, we present here the identification of the first single marker for MSI in gastric cancer, excelling with a specificity of 94% (16/17), sensitivity of 69.2% (9/13), negative predictive value of 80% (16/20), and positive predictive value of 90% (9/10). The TF antigen, detected by simple antibody-based assays, is highly specific for carcinoma being undetectable in gastric healthy and premalignant epithelia. This finding lays the basis for new studies and holds promise in improving the rapid identification of MSI in the clinical setting

Best Practice Recommendations for the Implementation of a Digital Pathology Workflow in the Anatomic Pathology Laboratory by the European Society of Digital and Integrative Pathology (ESDIP)

The interest in implementing digital pathology (DP) workflows to obtain whole slide image (WSI) files for diagnostic purposes has increased in the last few years. The increasing performance of technical components and the Food and Drug Administration (FDA) approval of systems for primary diagnosis led to increased interest in applying DP workflows. However, despite this revolutionary transition, real world data suggest that a fully digital approach to the histological workflow has been implemented in only a minority of pathology laboratories. The objective of this study is to facilitate the implementation of DP workflows in pathology laboratories, helping those involved in this process of transformation to identify: (a) the scope and the boundaries of the DP transformation; (b) how to introduce automation to reduce errors; (c) how to introduce appropriate quality control to guarantee the safety of the process and (d) the hardware and software needed to implement DP systems inside the pathology laboratory. The European Society of Digital and Integrative Pathology (ESDIP) provided consensus-based recommendations developed through discussion among members of the Scientific Committee. The recommendations are thus based on the expertise of the panel members and on the agreement obtained after virtual meetings. Prior to publication, the recommendations were reviewed by members of the ESDIP Board. The recommendations comprehensively cover every step of the implementation of the digital workflow in the anatomic pathology department, emphasizing the importance of interoperability, automation and tracking of the entire process before the introduction of a scanning facility. Compared to the available national and international guidelines, the present document represents a practical, handy reference for the correct implementation of the digital workflow in Europe