Deep learning for precise diagnosis and subtype triage of drug-resistant tuberculosis on chest computed tomography.

Deep learning, transforming input data into target prediction through intricate network structures, has inspired novel exploration in automated diagnosis based on medical images. The distinct morphological characteristics of chest abnormalities between drug-resistant tuberculosis (DR-TB) and drug-sensitive tuberculosis (DS-TB) on chest computed tomography (CT) are of potential value in differential diagnosis, which is challenging in the clinic. Hence, based on 1176 chest CT volumes from the equal number of patients with tuberculosis (TB), we presented a Deep learning-based system for TB drug resistance identification and subtype classification (DeepTB), which could automatically diagnose DR-TB and classify crucial subtypes, including rifampicin-resistant tuberculosis, multidrug-resistant tuberculosis, and extensively drug-resistant tuberculosis. Moreover, chest lesions were manually annotated to endow the model with robust power to assist radiologists in image interpretation and the Circos revealed the relationship between chest abnormalities and specific types of DR-TB. Finally, DeepTB achieved an area under the curve (AUC) up to 0.930 for thoracic abnormality detection and 0.943 for DR-TB diagnosis. Notably, the system demonstrated instructive value in DR-TB subtype classification with AUCs ranging from 0.880 to 0.928. Meanwhile, class activation maps were generated to express a human-understandable visual concept. Together, showing a prominent performance, DeepTB would be impactful in clinical decision-making for DR-TB.

The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID.

There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies. Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity. Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored. Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.

Radiogenomic System for Non-Invasive Identification of Multiple Actionable Mutations and PD-L1 Expression in Non-Small Cell Lung Cancer Based on CT Images.

PURPOSE: Personalized treatments such as targeted therapy and immunotherapy have revolutionized the predominantly therapeutic paradigm for non-small cell lung cancer (NSCLC). However, these treatment decisions require the determination of targetable genomic and molecular alterations through invasive genetic or immunohistochemistry (IHC) tests. Numerous previous studies have demonstrated that artificial intelligence can accurately predict the single-gene status of tumors based on radiologic imaging, but few studies have achieved the simultaneous evaluation of multiple genes to reflect more realistic clinical scenarios. METHODS: We proposed a multi-label multi-task deep learning (MMDL) system for non-invasively predicting actionable NSCLC mutations and PD-L1 expression utilizing routinely acquired computed tomography (CT) images. This radiogenomic system integrated transformer-based deep learning features and radiomic features of CT volumes from 1096 NSCLC patients based on next-generation sequencing (NGS) and IHC tests. RESULTS: For each task cohort, we randomly split the corresponding dataset into training (80%), validation (10%), and testing (10%) subsets. The area under the receiver operating characteristic curves (AUCs) of the MMDL system achieved 0.862 (95% confidence interval (CI), 0.758-0.969) for discrimination of a panel of 8 mutated genes, including EGFR, ALK, ERBB2, BRAF, MET, ROS1, RET and KRAS, 0.856 (95% CI, 0.663-0.948) for identification of a 10-molecular status panel (previous 8 genes plus TP53 and PD-L1); and 0.868 (95% CI, 0.641-0.972) for classifying EGFR / PD-L1 subtype, respectively. CONCLUSIONS: To the best of our knowledge, this study is the first deep learning system to simultaneously analyze 10 molecular expressions, which might be utilized as an assistive tool in conjunction with or in lieu of ancillary testing to support precision treatment options.

Immune regulation and emerging roles of noncoding RNAs in Mycobacterium tuberculosis infection.

Tuberculosis, caused by Mycobacterium tuberculosis, engenders an onerous burden on public hygiene. Congenital and adaptive immunity in the human body act as robust defenses against the pathogens. However, in coevolution with humans, this microbe has gained multiple lines of mechanisms to circumvent the immune response to sustain its intracellular persistence and long-term survival inside a host. Moreover, emerging evidence has revealed that this stealthy bacterium can alter the expression of demic noncoding RNAs (ncRNAs), leading to dysregulated biological processes subsequently, which may be the rationale behind the pathogenesis of tuberculosis. Meanwhile, the differential accumulation in clinical samples endows them with the capacity to be indicators in the time of tuberculosis suffering. In this article, we reviewed the nearest insights into the impact of ncRNAs during Mycobacterium tuberculosis infection as realized via immune response modulation and their potential as biomarkers for the diagnosis, drug resistance identification, treatment evaluation, and adverse drug reaction prediction of tuberculosis, aiming to inspire novel and precise therapy development to combat this pathogen in the future.

Emerging Role of Noncoding RNAs in EGFR TKI-Resistant Lung Cancer.

Lung cancer accounts for the majority of malignancy-related mortalities worldwide. The introduction of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment and significantly improved the overall survival (OS) of lung cancer. Nevertheless, almost all EGFR-mutant patients invariably acquire TKI resistance. Accumulating evidence has indicated that noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), have a central role in the tumorigenesis and progression of lung cancer by regulating crucial signaling pathways, providing a new approach for exploring the underlying mechanisms of EGFR-TKI resistance. Therefore, this review comprehensively describes the dysregulation of ncRNAs in EGFR TKI-resistant lung cancer and its underlying mechanisms. We also underscore the clinical application of ncRNAs as prognostic, predictive and therapeutic biomarkers for EGFR TKI-resistant lung cancer. Furthermore, the barriers that need to be overcome to translate the basic findings of ncRNAs into clinical practice are discussed.

The Application of Artificial Intelligence in the Diagnosis and Drug Resistance Prediction of Pulmonary Tuberculosis.

With the increasing incidence and mortality of pulmonary tuberculosis, in addition to tough and controversial disease management, time-wasting and resource-limited conventional approaches to the diagnosis and differential diagnosis of tuberculosis are still awkward issues, especially in countries with high tuberculosis burden and backwardness. In the meantime, the climbing proportion of drug-resistant tuberculosis poses a significant hazard to public health. Thus, auxiliary diagnostic tools with higher efficiency and accuracy are urgently required. Artificial intelligence (AI), which is not new but has recently grown in popularity, provides researchers with opportunities and technical underpinnings to develop novel, precise, rapid, and automated implements for pulmonary tuberculosis care, including but not limited to tuberculosis detection. In this review, we aimed to introduce representative AI methods, focusing on deep learning and radiomics, followed by definite descriptions of the state-of-the-art AI models developed using medical images and genetic data to detect pulmonary tuberculosis, distinguish the infection from other pulmonary diseases, and identify drug resistance of tuberculosis, with the purpose of assisting physicians in deciding the appropriate therapeutic schedule in the early stage of the disease. We also enumerated the challenges in maximizing the impact of AI in this field such as generalization and clinical utility of the deep learning models.