CoNIC Challenge: Pushing the Frontiers of Nuclear Detection, Segmentation, Classification and Counting

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery

Characteristics of Epidermal Growth Factor Receptor with Rare Mutations in Non-small Cell Lung Cancer and the Effect of EGFR Tyrosine Kinase Inhibitors on Them

Background and objective Adenocarcinoma is the most common type of lung cancer. It has been clinically evaluated that therapiestargeting against the epidermal growth factor receptor (EGFR) as the clinical standard first-line treatment. The response and outcome of EGFR-tyrosine kinase inhibitors (TKIs) in patients harboring common mutations in EGFR kinase domain (deletion in exon19 and L858R in exon 21) has been well demonstrated, but not in rare or complex mutations. Methods A total of 150 patients that harbored rare or complex mutations in EGFR diagnosed by histopathology were included in this retrospective study. The clinical-pathological characteristics of all 150 patients as well as the response and progression-free survival (PFS) in 48 patients that received EGFR-TKIs in first/second/third line treatments weredescribed and analyzed. Results Patients were divided into four groups based on the mutation types: single G719X point mutation in exon 18 (n=46, 30.7%), single L861Q point mutation in exon 21 (n=45, 30.0%), other single rare mutation (n=14, 9.3%) and complex mutations (n=45, 30.0%). The result indicated thatthere was no correlation of EGFR mutation typeswith other parameters such as gender, age, clinical stage, pathology and smoking history. For the 48 patients that received EGFR-TKIs treatment, there were no significant differencesamong 4 groups in terms of objective response rate (ORR) and disease control rate (DCR) (54.5% vs 30.0% vs 0.0% vs 35.7%, χ2=3.200, P=0.34; 90.9% vs 85.0% vs 66.7% vs 92.9%, χ2=2.162, P=0.59). The median progress-free survival (mPFS) was 11.0 months (95%CI: 4.4-17.6), and in each group of different EGFR mutation types are 15.8 months (95%CI: 9.5-22.2), 8.0 months (95%CI: 5.1-11.0), 4.9 months (95%CI: 1.4-8.4) and 23.1 months (95%CI: 15.8-30.4)(χ2=7.876, P=0.049). Conclusion The efficiency of targeting EGFR-TKIs on different types of rare or complex mutations was heterogeneous. The PFS may be better in patients that harbored complex mutations than those with single rare mutations. Further studies with larger sample size are necessary. Moreover, to discover novel therapeutic targets and develop new drugs are imminentfor those patientswith no response to the existing treatments

The temporal dynamics of first and second language processing: ERPs to spoken words in Mandarin-English bilinguals

© 2020 Elsevier Ltd The dynamics of bilingual spoken word recognition remain poorly characterized, especially for individuals who speak two languages that are highly dissimilar in their phonological and morphological structure. The present study compared first language (L1) and second language (L2) spoken word processing within a group of adult Mandarin-English bilinguals (N = 34; ages 18–25). Event-related potentials (ERPs) were recorded while participants completed the same cross-modal matching task separately in their L1 Mandarin and L2 English. This task consisted of deciding whether spoken words matched pictures of items. Pictures and spoken words either matched (e.g., Mandarin: TANG2-tang2; English: BELL-bell), or differed in word-initial phonemes (e.g., Mandarin: TANG2-lang2; English: BELL-shell), word-final phonemes (e.g., Mandarin: TANG2-tao2; English: BELL-bed), or whole words (e.g., Mandarin: TANG2-xia1: English: BELL-ham). Each mismatch type was associated with a pattern of modulation of the Phonological Mapping Negativity, the N400, and the Late N400 that was distinct from those of the other mismatch types yet similar between the two languages. This was interpreted as evidence of incremental processing with similar temporal dynamics in both languages. These findings support models of spoken word recognition in bilingual individuals that adopt an interactive-activation framework for both L1 and L2 processing