Classification of drug-resistant tuberculosis (DR-TB) and drug-sensitive tuberculosis (DS-TB) from chest radiographs remains an open problem. Our previous cross validation performance on publicly available chest X-ray (CXR) data combined with image augmentation, the addition of synthetically generated and publicly available images achieved a performance of 85% AUC with a deep convolutional neural network (CNN). However, when we evaluated the CNN model trained to classify DR-TB and DS-TB on unseen data, significant performance degradation was observed (65% AUC). Hence, in this paper, we investigate the generalizability of our models on images from a held out country's dataset. We explore the extent of the problem and the possible reasons behind the lack of good generalization. A comparison of radiologist-annotated lesion locations in the lung and the trained model's localization of areas of interest, using GradCAM, did not show much overlap. Using the same network architecture, a multi-country classifier was able to identify the country of origin of the X-ray with high accuracy (86%), suggesting that image acquisition differences and the distribution of non-pathological and non-anatomical aspects of the images are affecting the generalization and localization of the drug resistance classification model as well. When CXR images were severely corrupted, the performance on the validation set was still better than 60% AUC. The model overfitted to the data from countries in the cross validation set but did not generalize to the held out country. Finally, we applied a multi-task based approach that uses prior TB lesions location information to guide the classifier network to focus its attention on improving the generalization performance on the held out set from another country to 68% AUC.
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http://dx.doi.org/10.3390/diagnostics12010188 | DOI Listing |
BMJ Open
January 2025
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
Introduction: Non-adherence to tuberculosis (TB) treatment poses a significant challenge to effective TB management globally and is a major contributor to the emergence of multidrug-resistant TB. Although adherence to TB treatment has been widely studied, a comprehensive evaluation of the comparative levels of adherence in high- versus low-TB burden settings remains lacking. The objective of this systematic review and meta-analysis is to assess the levels of adherence to TB treatment in high-TB burden countries compared to low-burden countries.
View Article and Find Full Text PDFMol Divers
January 2025
Department of Laboratory Medicine, The Fourth People's Hospital of Nanhai District of Foshan City, Foshan, 528000, Guangdong, China.
Disruption of the mycobacterial redox homeostasis leads to irreversible stress induction and cell death. Hydroquinone scaffolds, as a new type of redox cycling anti-tuberculosis chemotypes, exhibit potent bactericidal activity against non-replicating, nutrient-deprived phenotypically drug-resistant bacteria. Evidences from microbiological, biochemical, and genetic studies indicate that the redox-driven mode of action relies on the reduction of quinones by type II NADH dehydrogenase (NDH2), generating reactive oxygen species (ROS) of bactericidal level.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
infections continue to pose a significant global health challenge, particularly due to the rise of multidrug-resistant strains, random mycobacterial mutations, and the complications associated with short-term antibiotic regimens. Currently, five approved drugs target cell wall biosynthesis in . This review provides a comprehensive analysis of these drugs and their molecular mechanisms.
View Article and Find Full Text PDFPathogens
January 2025
Department of Clinical Laboratory, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Institute, Capital Medical University, Beijing 101100, China.
The aim of this study was to reveal diagnostic biomarkers of considerable importance for common pathogenic , utilizing pan-genomic and comparative genome analysis to accurately characterize clinical infections. In this study, complete or assembled genome sequences of common pathogenic and closely related species were obtained from NCBI as discovery and validation sets, respectively. Genome annotation was performed using Prokka software, and pan-genomic analysis and extraction of core genes were performed using BPGA software.
View Article and Find Full Text PDFMicroorganisms
December 2024
Bach Institute of Biochemistry, Fundamentals of Biotechnology, Federal Research Center, Russian Academy of Sciences, Moscow 119071, Russia.
(Mtb) is one of the most successful bacterial pathogens in human history. Even in the antibiotic era, Mtb is widespread and causes millions of new cases of tuberculosis each year. The ability to disrupt the host's innate and adaptive immunity, as well as natural persistence, complicates disease control.
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