Development and validation of a prognostic model for HER2-low breast cancer to evaluate neoadjuvant therapy.

Background: Human epidermal growth factor receptor 2 (HER2) low breast cancer (BC) accounts for 30-51% of all BCs. How to precisely assess the response to neoadjuvant therapy in this heterogenous tumor is currently unanswered. With the advance in multi-omics, refining the molecular subtyping other than the current hormone receptor (HR)-based subtyping to guide the neoadjuvant therapy for HER2-low BC is potentially feasible. Methods: The messenger RNA (mRNA), clinical, and pathological data of all HER2-low BC patients (n=368) from the Neoadjuvant I-SPY2 Trial, were retrieved. Ninety-eight patients achieved pathological complete response (pCR) were randomly divided into the training and validation sets with 8:2 ratio. The non-pCR cases were corporated into the above datasets with 1:1 ratio. The rest non-pCR cases were served as the test set. Random forest (RF), support vector machine (SVM), and fully connected neural network (FCNN) were applied to establish a 1-dimensional (1D) model based on mRNA data. The method with best prediction value among the 3 models was selected for further modeling when combining pathological features. A new classification of deep learning (CDn) was proposed based on a multi-omics model. After identifying pCR-related features by the integral gradient and unsupervised hierarchical clustering method, the responses to neoadjuvant therapy associated with these features across different subgroups were analyzed. Results: Compared with the RF and SVM models, the FCNN model achieved the best performance [area under the curve (AUC): 0.89] based on the mRNA feature. By combining mRNA and pathological features, the FCNN model proposed 2 new subtypes including CD1 and CD0 for HER2-low BC. CD1 increased the sensitivity to predict pCR by 23.5% [to 87.8%; 95% confidence interval (CI): 78% to 94%] and improved the specificity to pCR by 12.2% (to 77.4%; 95% CI: 69% to 87%) when comparing with the current HR classification for HER2-low BC. Conclusions: The new typing method (CD1 and CD0) proposed in this study achieved excellent performance for predicting the pCR to neoadjuvant therapy in HER2-low BC. The patients who were not sensitive to neoadjuvant therapy according to multi-omics models might receive surgical treatment directly.

Small lesion classification on abbreviated breast MRI: training can improve diagnostic performance and inter-reader agreement.

OBJECTIVE: To determine whether the diagnostic performance and inter-reader agreement for small lesion classification on abbreviated breast MRI (AB-MRI) can be improved by training, and can achieve the level of full diagnostic protocol MRI (FDP-MRI). METHODS: This retrospective study enrolled 1165 breast lesions (≤ 2 cm; 409 malignant and 756 benign) from 1165 MRI examinations for reading test. Twelve radiologists were assigned into a trained group and a non-trained group. They interpreted each AB-MRI twice, which was extracted from FDP-MRI. After the first read, the trained group received a structured training for AB-MRI interpretation while the non-trained group did not. FDP-MRIs were interpreted by the trained group after the second read. BI-RADS category for each lesion was compared to the standard of reference (histopathological examination or follow-up) to calculate diagnostic accuracy. Inter-reader agreement was assessed using multirater k analysis. Diagnostic accuracy and inter-reader agreement were compared between the trained and non-trained groups, between the first and second reads, and between AB-MRI and FDP-MRI. RESULTS: After training, the diagnostic accuracy of AB-MRI increased from 77.6 to 84.4%, and inter-reader agreement improved from 0.410 to 0.579 (both p < 0.001), which were higher than those of the non-trained group (accuracy, 84.4% vs 78.0%; weighted k, 0.579 vs 0.461; both p < 0.001). The post-training accuracy and inter-reader agreement of AB-MRI were lower than those of FDP-MRI (accuracy, 84.4% vs 92.8%; weighted k, 0.579 vs 0.602; both p < 0.001). CONCLUSIONS: Training can improve the diagnostic performance and inter-reader agreement for small lesion classification on AB-MRI; however, it remains inferior to those of FDP-MRI. KEY POINTS: • Training can improve the diagnostic performance for small breast lesions on AB-MRI. • Training can reduce inter-observer variation for breast lesion classification on AB-MRI, especially among junior radiologists. • The post-training diagnostic performance and inter-reader agreement of AB-MRI remained inferior to those of FDP-MRI.

Growth and Toxin Production of Gambierdiscus spp. Can Be Regulated by Quorum-Sensing Bacteria.

Gambierdiscus spp. are the major culprit responsible for global ciguatera fish poisoning (CFP). At present, the effects of microbiological factors on algal proliferation and toxin production are poorly understood. To evaluate the regulatory roles of quorum-sensing (QS) bacteria in the physiology of Gambierdiscus, co-culture experiments with screened QS strains were conducted in this study. Except for the growth-inhibiting effect from the strain Marinobacter hydrocarbonoclasticus, the algal host generally displayed much higher growth potential and toxin production ability with the existence of QS strains. In addition, Bacillus anthracis particularly exhibited a broad-spectrum growth enhancement effect on various Gambierdiscus types, as well as a remarkable influence on algal toxicity. The variations of algal physiological status, including growth rate, chlorophyll content, and responsive behaviors, are potential reasons for the observed positive or negative affection. This study suggests that QS bacteria regulate the algal growth and toxin production. Based on the evidence, we further speculate that QS bacteria may contribute to the site-specific distribution of CFP risk through regulating the algal host biomass and toxicity.

Congenital calcinosis cutis of the ear.

Congenital calcinosis cutis is a relatively rare event. Herein we report 3 cases of congenital calcinosis cutis that all appeared in the exact same location on the ear. A possible mechanism of pathogenesis is discussed.

Cutaneous manifestations of hyper-IgE syndrome in infants and children.

We describe 8 children with hyper-IgE syndrome who had papulopustular eruption on the face and scalp in the first year of life. Seven of the 8 patients had persistent peripheral eosinophilia and 3 had leukocytosis noted before diagnosis. Skin biopsy specimens in 6 patients revealed spongiosis and perivascular dermatitis and/or folliculitis with a predominance of eosinophils. Two patients had bone fractures and osteopenia. Recurrent pneumonia occurred in 6 children and pneumatoceles in 5. The diagnosis of hyper-IgE syndrome was made an average of 18 months after the onset of the initial papulopustular eruption. These findings may lead to earlier recognition of the disease and institution of appropriate treatment.