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Objective Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis.Design We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase 1, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase 2, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.Results We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen’s kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen’s kappa coefficient of 0.67 (±0.09).Conclusion We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited interobserver agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the importance of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using artificial intelligence.

ObjectiveIn this study, we investigated pivotal molecular markers in human high-grade breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) was measured among various subtypes (Luminal (Lum) A, LumB HER2-, LumB HER2+, HER2-enriched and triple-negative).MethodsIn total, 357 DCIS cases were classified into respective subtypes, according to the 2013 St. Gallen guidelines. Each subtype was categorized into three subcategories: “Pure” (those without an invasive component), “W/invasive” (those with an invasive component), and “All” (the entire group of the given subtype). ER and PR expression were registered as intervals. Equivocal HER2 immunohistochemistry (IHC) cases (2+) were further investigated using dual-color in situ hybridization.ResultsThe majority of patients (71%) were over the age of 50. We discovered no significant differences in the proportion of age between the “Pure” and “W/invasive” groups. There was no significant difference in ER/PR expression between “Pure” luminal subtypes of DCIS and “W/invasive” cases. We compared the HER2 IHC scores of “0”, “1+”, and “2+” among LumA and LumB HER2 subtypes and identified no statistically significant differences between “Pure” and “W/invasive” (p = 0.603). ER and PR expression ≥ 50% cutoff value was present in > 90% of all LumA cases. The incidences of cases with ER expression at cutoff values of < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). The proportion of cases with PR expression < 20% showed significant differences in the various luminal subtypes. In luminal B subtypes, low PR expression (< 20%) was significantly associated with both strong HER2 expression (3+) and the presence of an invasive component (p = 0.0001 and p = 0.0365, respectively).ConclusionsER and PR expression at ≥ 50% cutoff values were found in more than 90% of LumA cases. Samples with ER < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). Low PR expression in high-grade DCIS was strongly associated with HER2 overexpression (3+) and an invasive component (p = 0.0001 and p = 0.0365, respectively).

In distributed computing, a Byzantine fault is a condition where a component behaves inconsistently, showing different symptoms to different components of the system. Consensus among the correct components can be reached by appropriately crafted communication protocols even in the presence of byzantine faults. Quantum-aided protocols built upon distributed entangled quantum states are worth considering, as they are more resilient than traditional ones. Based on earlier ideas, here we establish a parameter-dependent family of quantum-aided weak broadcast protocols. We compute upper bounds on the failure probability of the protocol, and define and illustrate a procedure that minimizes the quantum resource requirements. Following earlier work demonstrating the suitability of noisy intermediate scale quantum (NISQ) devices for the study of quantum networks, we experimentally create our resource quantum state on publicly available quantum computers. Our work highlights important engineering aspects of the future deployment of quantum communication protocols with multi-qubit entangled states.