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Importance Epstein-Barr virus (EBV)–associated gastric cancer (EBV-GC) is 1 of 4 molecular subtypes of GC and is confirmed by an expensive molecular test, EBV-encoded small RNA in situ hybridization. EBV-GC has 2 histologic characteristics, lymphoid stroma and lace-like tumor pattern, but projecting EBV-GC at biopsy is difficult even for experienced pathologists. Objective To develop and validate a deep learning algorithm to predict EBV status from pathology images of GC biopsy. Design, Setting, and Participants This diagnostic study developed a deep learning classifier to predict EBV-GC using image patches of tissue microarray (TMA) and whole slide images (WSIs) of GC and applied it to GC biopsy specimens from GCs diagnosed at Kangbuk Samsung Hospital between 2011 and 2020. For a quantitative evaluation and EBV-GC prediction on biopsy specimens, the area of each class and the fraction in total tissue or tumor area were calculated. Data were analyzed from March 5, 2021, to February 10, 2022. Main Outcomes and Measures Evaluation metrics of predictive model performance were assessed on accuracy, recall, precision, F1 score, area under the receiver operating characteristic curve (AUC), and κ coefficient. Results This study included 137 184 image patches from 16 TMAs (708 tissue cores), 24 WSIs, and 286 biopsy images of GC. The classifier was able to classify EBV-GC image patches from TMAs and WSIs with 94.70% accuracy, 0.936 recall, 0.938 precision, 0.937 F1 score, and 0.909 κ coefficient. The classifier was used for predicting and measuring the area and fraction of EBV-GC on biopsy tissue specimens. A 10% cutoff value for the predicted fraction of EBV-GC to tissue (EBV-GC/tissue area) produced the best prediction results in EBV-GC biopsy specimens and showed the highest AUC value (0.8723; 95% CI, 0.7560-0.9501). That cutoff also obtained high sensitivity (0.895) and moderate specificity (0.745) compared with experienced pathologist sensitivity (0.842) and specificity (0.854) when using the presence of lymphoid stroma and a lace-like pattern as diagnostic criteria. On prediction maps, EBV-GCs with lace-like pattern and lymphoid stroma showed the same prediction results as EBV-GC, but cases lacking these histologic features revealed heterogeneous prediction results of EBV-GC and non–EBV-GC areas. Conclusions and Relevance This study showed the feasibility of EBV-GC prediction using a deep learning algorithm, even in biopsy samples. Use of such an image-based classifier before a confirmatory molecular test will reduce costs and tissue waste.

There is no doubt that advanced artificial intelligence models and high quality data are the keys to success in developing computational pathology tools. Although the overall volume of pathology data keeps increasing, a lack of quality data is a common issue when it comes to a specific task due to several reasons including privacy and ethical issues with patient data. In this work, we propose to exploit knowledge distillation, i.e., utilize the existing model to learn a new, target model, to overcome such issues in computational pathology. Specifically, we employ a student-teacher framework to learn a target model from a pre-trained, teacher model without direct access to source data and distill relevant knowledge via momentum contrastive learning with multi-head attention mechanism, which provides consistent and context-aware feature representations. This enables the target model to assimilate informative representations of the teacher model while seamlessly adapting to the unique nuances of the target data. The proposed method is rigorously evaluated across different scenarios where the teacher model was trained on the same, relevant, and irrelevant classification tasks with the target model. Experimental results demonstrate the accuracy and robustness of our approach in transferring knowledge to different domains and tasks, outperforming other related methods. Moreover, the results provide a guideline on the learning strategy for different types of tasks and scenarios in computational pathology. Code is available at: \\url{https://github.com/trinhvg/MoMA}.

Slide-level classification for whole-slide images (WSIs) has been widely recognized as a crucial problem in digital and computational pathology. Current approaches commonly consider WSIs as a bag of cropped patches and process them via multiple instance learning due to the large number of patches, which cannot fully explore the relationship among patches; in other words, the global information cannot be fully incorporated into decision making. Herein, we propose an efficient and effective slide-level classification model, named as FALFormer, that can process a WSI as a whole so as to fully exploit the relationship among the entire patches and to improve the classification performance. FALFormer is built based upon Transformers and self-attention mechanism. To lessen the computational burden of the original self-attention mechanism and to process the entire patches together in a WSI, FALFormer employs Nystr\"om self-attention which approximates the computation by using a smaller number of tokens or landmarks. For effective learning, FALFormer introduces feature-aware landmarks to enhance the representation power of the landmarks and the quality of the approximation. We systematically evaluate the performance of FALFormer using two public datasets, including CAMELYON16 and TCGA-BRCA. The experimental results demonstrate that FALFormer achieves superior performance on both datasets, outperforming the state-of-the-art methods for the slide-level classification. This suggests that FALFormer can facilitate an accurate and precise analysis of WSIs, potentially leading to improved diagnosis and prognosis on WSIs.

Recently, vision-language pre-trained models have emerged in computational pathology. Previous works generally focused on the alignment of image-text pairs via the contrastive pre-training paradigm. Such pre-trained models have been applied to pathology image classification in zero-shot learning or transfer learning fashion. Herein, we hypothesize that the pre-trained vision-language models can be utilized for quantitative histopathology image analysis through a simple image-to-text retrieval. To this end, we propose a Text-based Quantitative and Explainable histopathology image analysis, which we call TQx. Given a set of histopathology images, we adopt a pre-trained vision-language model to retrieve a word-of-interest pool. The retrieved words are then used to quantify the histopathology images and generate understandable feature embeddings due to the direct mapping to the text description. To evaluate the proposed method, the text-based embeddings of four histopathology image datasets are utilized to perform clustering and classification tasks. The results demonstrate that TQx is able to quantify and analyze histopathology images that are comparable to the prevalent visual models in computational pathology.

The appearance of histopathology images depends on tissue type, staining and digitization procedure. These vary from source to source and are the potential causes for domain-shift problems. Owing to this problem, despite the great success of deep learning models in computational pathology, a model trained on a specific domain may still perform sub-optimally when we apply them to another domain. To overcome this, we propose a new augmentation called PatchShuffling and a novel self-supervised contrastive learning framework named IMPaSh for pre-training deep learning models. Using these, we obtained a ResNet50 encoder that can extract image representation resistant to domain-shift. We compared our derived representation against those acquired based on other domain-generalization techniques by using them for the cross-domain classification of colorectal tissue images. We show that the proposed method outperforms other traditional histology domain-adaptation and state-of-the-art self-supervised learning methods. Code is available at: https://github.com/trinhvg/IMPash .

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.

Reading practices play an important role in the learning process of students. Especially in a fast-changing world where knowledge about nature and society is in a constant state of flux, book reading helps students foster skills such as thinking, valuing, adaptability and creativity for sustainable development. This research study used a dataset of 1676 observations of junior high school students from Northern Vietnam to explore students’ academic achievement and its association with their reading passion, family socio economic condition, parental education and occupational aspiration. The empirical results show that higher grades in STEM-related subjects are predicted by reading interest (βReadbook = 0.425, p < 0.0001), with students who love reading books achieve higher score than those who take no interest in books. Remarkably, the education level of the mother strongly enhances academic performance, with β = 0.721 (p < 0.0001) in cases of mother having a university diploma or higher. Students coming from wealthy families are more likely to buy books whereas borrowing from the library is the main source of books for students who grow up in not-rich families. However, even among wealthy families, investment into buying books still rely more on personal interest, despite the aforementioned educational benefits of book reading, as evidenced by an over 7 percentage point disparity between the likelihood of purchasing books among wealthy-family students who took an interest in reading (45%) versus students of the same background who did not like to read (38.7%). The results present implications for education policy making with a vision towards United Nations’ Sustainable Development Goal 4: Quality Education.

We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions.

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X–S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X–S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. Clinical features, such as coma, can predict death, but they are insufficient for the accurate prognosis of other outcomes, especially when impacted by co-morbidities such as HIV infection. Brain magnetic resonance imaging (MRI) characterises the extent and severity of disease and may enable more accurate prediction of complications and poor outcomes. We analysed clinical and brain MRI data from a prospective longitudinal study of 216 adults with TBM; 73 (34%) were HIV-positive, a factor highly correlated with mortality. We implemented an end-to-end framework to model clinical and imaging features to predict disease progression. Our model used state-of-the-art machine learning models for automatic imaging feature encoding, and time-series models for forecasting, to predict TBM progression. The proposed approach is designed to be robust to missing data via a novel tailored model optimisation framework. Our model achieved a 60% balanced accuracy in predicting the prognosis of TBM patients over the six different classes. HIV status did not alter the performance of the models. Furthermore, our approach identified brain morphological lesions caused by TBM in both HIV and non-HIV-infected, associating lesions to the disease staging with an overall accuracy of 96%. These results suggest that the lesions caused by TBM are analogous in both populations, regardless of the severity of the disease. Lastly, our models correctly identified changes in disease symptomatology and severity in 80% of the cases. Our approach is the first attempt at predicting the prognosis of TBM by combining imaging and clinical data, via a machine learning model. The approach has the potential to accurately predict disease progression and enable timely clinical intervention.