INTRODUCTION: The histopathological classification for antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (ANCA-GN) is a well-established tool to reflect the variety of patterns and severity of lesions that can occur in kidney biopsies. It was demonstrated previously that deep learning (DL) approaches can aid in identifying histopathological classes of kidney diseases; for example, of diabetic kidney disease. These models can potentially be used as decision support tools for kidney pathologists. Although they reach high prediction accuracies, their "black box" structure makes them nontransparent. Explainable (X) artificial intelligence (AI) techniques can be used to make the AI model decisions accessible for human experts. We have developed a DL-based model, which detects and classifies the glomerular lesions according to the Berden classification. METHODS: Kidney biopsy slides of 80 patients with ANCA-GN from 3 European centers, who underwent a diagnostic kidney biopsy between 1991 and 2011, were included. We also investigated the explainability of our model using Gradient-weighted Class Activation Mapping (Grad-CAM) heatmaps. These maps were analyzed by pathologists to compare the decision-making criteria of humans and the DL model and assess the impact of different training settings. RESULTS: The DL model shows a prediction accuracy of 93% for classifying lesions. The heatmaps from our trained DL models showed that the most predictive areas in the image correlated well with the areas deemed to be important by the pathologist. CONCLUSION: We present the first DL-based computational pipeline for classifying ANCA-GN kidney biopsies as per the Berden classification. XAI techniques helped us to make the decision-making criteria of the DL accessible for renal pathologists, potentially improving clinical decision-making.

• Publication type
• Journal Article MeSH

Práce se zabývá využitím algoritmů umělé inteligence (artificial intelligence – AI) v diagnostice karcinomu prsu, plic a prostaty. Popisuje historický vývoj digitalizace patologických procesů, implementaci umělé inteligence a její současné aplikace v patologii. Zaměřuje se na strojové a hluboké učení, počítačové vidění a digitální patologii, které přispívají k automatizaci a zpřesnění diagnostiky. Důraz je kladen na konkrétní nástroje, jako jsou systémy uPath od Roche a IBEX Medical Analytics, které umožňují analýzu histopatologických snímků, klasifikaci nádorových buněk a hodnocení biomarkerů. Práce také reflektuje výhody využití AI, včetně zvýšení přesnosti diagnostiky a efektivity laboratorních procesů, ale zároveň upozorňuje na výzvy spojené s její implementací, jako jsou etické a právní aspekty, ochrana osobních údajů a odpovědnost za chyby. Cílem práce je poskytnout komplexní přehled o možnostech využití AI v digitální patologii a její roli v moderní onkologické diagnostice.

The study focuses on the utilization of artificial intelligence (AI) algorithms in the diagnosis of breast, lung, and prostate cancer. It describes the historical development of the digitalization of pathological processes, the implementation of artificial intelligence, and its current applications in pathology. The study emphasizes machine learning, deep learning, computer vision, and digital pathology, which contribute to the automation and refinement of diagnostics. Special attention is given to specific tools such as the uPath systems from Roche and IBEX Medical Analytics, which enable the analysis of histopathological images, tumor cell classification, and biomarker evaluation. The study also highlights the benefits of AI utilization, including increased diagnostic accuracy and efficiency in laboratory processes, while simultaneously addressing the challenges associated with its implementation, such as ethical and legal considerations, data protection, and liability for errors. The aim of this study is to provide a comprehensive overview of the potential applications of AI in digital pathology and its role in modern oncological diagnostics.

Tento článek zpracovává téma nových trendů a technologií v urologii, a to konkrétně v oblasti telemedicíny a umělé inteligence. Nejprve stručně pojednává o přínosech telemedicíny a jak mění pohled na vztah mezi lékařem a pacientem. Podrobněji se pak text věnuje především umělé inteligenci, jež se v současnosti dostává do popředí zájmu laické i odborné veřejnosti. Její potenciál v urologii je testován v mnoha studiích, především se zaměřením na uroonkologii, v menší míře pak také v oblasti benigních urologických onemocnění. Článek se snaží identifikovat nejvýznamnější pokroky v této rychle se rozvíjející oblasti, a zároveň předkládá současné limity jejího zapojení do klinické praxe.

This article explores the emerging trends and technologies in urology, focusing on telemedicine and artificial intelligence. It provides a brief overview of the benefits of telemedicine and its impact on the patient-physician interactions. The article subsequently explores in detail the use of artificial intelligence, which is currently gaining considerable interest from both general public and medical professionals. Its potential in urology has been tested in a number of clinical studies, particularly in the field of uro-oncology and, to a lesser extent, in benign urological diseases. The aim of this article is to identify the key advances in this rapidly evolving field, while also highlighting the current limitations of its implementation into clinical practice.

• MeSH
• Deep Learning MeSH
• Humans MeSH
• Robotic Surgical Procedures MeSH
• Machine Learning MeSH
• Telemedicine MeSH
• Artificial Intelligence MeSH
• Urologic Neoplasms diagnosis   therapy   MeSH
• Urology * trends   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

This study presents an automated, objective method for eyelid movement assessment in de-novo Parkinson's disease(PD) using a one-dimensional camera setup during monologue. These measurements were related to Dopamine Transporter Single Photon Emission Tomography and clinical scores. State-of-the-art computer-vision technologies and deep-learning neural networks were utilized to measure fourteen eyelid movement markers describing blinking and eyelid kinematics. Video-recordings were collected from a total of 120 de-novo patients with PD and 55 healthy controls. Abnormal blinking was present in 38% of PD, indicated by a reduced blink rate (p < 0.001), an increased inter-blink interval (p < 0.001), and an increased rigidity of the palpebral aperture (p < 0.001). The classification experiment reached an area under the curve of 0.81 on a blinded test set. The blink rate correlated with the loss of nigral dopaminergic neurons (r = 0.35, p < 0.001). These findings suggest eyelid movement markers as strong reflections of striatal dopaminergic activity levels, underscoring the method's potential as a reliable early PD biomarker.

• Publication type
• Journal Article MeSH

• Keywords
• studie ACCESS,
• MeSH
• Detection Algorithms MeSH
• Diabetes Mellitus MeSH
• Diabetic Retinopathy * diagnosis   prevention & control   MeSH
• Health Services Accessibility MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Diagnostic Screening Programs * MeSH
• Artificial Intelligence * MeSH
• Insurance, Health MeSH
• Check Tag
• Humans MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: Use of artificial intelligence (AI) in rare diseases has grown rapidly in recent years. In this review we have outlined the most common machine-learning and deep-learning methods currently being used to classify and analyse large amounts of data, such as standardized images or specific text in electronic health records. To illustrate how these methods have been adapted or developed for use with rare diseases, we have focused on Fabry disease, an X-linked genetic disorder caused by lysosomal α-galactosidase. A deficiency that can result in multiple organ damage. METHODS: We searched PubMed for articles focusing on AI, rare diseases, and Fabry disease published anytime up to 08 January 2025. Further searches, limited to articles published between 01 January 2021 and 31 December 2023, were also performed using double combinations of keywords related to AI and each organ affected in Fabry disease, and AI and rare diseases. RESULTS: In total, 20 articles on AI and Fabry disease were included. In the rare disease field, AI methods may be applied prospectively to large populations to identify specific patients, or retrospectively to large data sets to diagnose a previously overlooked rare disease. Different AI methods may facilitate Fabry disease diagnosis, help monitor progression in affected organs, and potentially contribute to personalized therapy development. The implementation of AI methods in general healthcare and medical imaging centres may help raise awareness of rare diseases and prompt general practitioners to consider these conditions earlier in the diagnostic pathway, while chatbots and telemedicine may accelerate patient referral to rare disease experts. The use of AI technologies in healthcare may generate specific ethical risks, prompting new AI regulatory frameworks aimed at addressing these issues to be established in Europe and the United States. CONCLUSION: AI-based methods will lead to substantial improvements in the diagnosis and management of rare diseases. The need for a human guarantee of AI is a key issue in pursuing innovation while ensuring that human involvement remains at the centre of patient care during this technological revolution.

• MeSH
• Fabry Disease * diagnosis   MeSH
• Humans MeSH
• Artificial Intelligence * MeSH
• Rare Diseases * diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Protein misfolding diseases, including α1-antitrypsin deficiency (AATD), pose substantial health challenges, with their cellular progression still poorly understood1-3. We use spatial proteomics by mass spectrometry and machine learning to map AATD in human liver tissue. Combining Deep Visual Proteomics (DVP) with single-cell analysis4,5, we probe intact patient biopsies to resolve molecular events during hepatocyte stress in pseudotime across fibrosis stages. We achieve proteome depth of up to 4,300 proteins from one-third of a single cell in formalin-fixed, paraffin-embedded tissue. This dataset reveals a potentially clinically actionable peroxisomal upregulation that precedes the canonical unfolded protein response. Our single-cell proteomics data show α1-antitrypsin accumulation is largely cell-intrinsic, with minimal stress propagation between hepatocytes. We integrated proteomic data with artificial intelligence-guided image-based phenotyping across several disease stages, revealing a late-stage hepatocyte phenotype characterized by globular protein aggregates and distinct proteomic signatures, notably including elevated TNFSF10 (also known as TRAIL) amounts. This phenotype may represent a critical disease progression stage. Our study offers new insights into AATD pathogenesis and introduces a powerful methodology for high-resolution, in situ proteomic analysis of complex tissues. This approach holds potential to unravel molecular mechanisms in various protein misfolding disorders, setting a new standard for understanding disease progression at the single-cell level in human tissue.

• MeSH
• alpha 1-Antitrypsin metabolism   MeSH
• Single-Cell Analysis MeSH
• alpha 1-Antitrypsin Deficiency * pathology   metabolism   genetics   MeSH
• Phenotype MeSH
• Hepatocytes metabolism   pathology   MeSH
• Liver Cirrhosis pathology   metabolism   MeSH
• Liver pathology   metabolism   MeSH
• Humans MeSH
• Disease Progression MeSH
• Proteome * analysis   metabolism   MeSH
• Proteomics * methods   MeSH
• Unfolded Protein Response MeSH
• Machine Learning MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Targeting ubiquitin E3 ligases is therapeutically attractive; however, the absence of an active-site pocket impedes computational approaches for identifying inhibitors. In a large, unbiased biochemical screen, we discover inhibitors that bind a cryptic cavity distant from the catalytic cysteine of the homologous to E6-associated protein C terminus domain (HECT) E3 ligase, SMAD ubiquitin regulatory factor 1 (SMURF1). Structural and biochemical analyses and engineered escape mutants revealed that these inhibitors restrict an essential catalytic motion by extending an α helix over a conserved glycine hinge. SMURF1 levels are increased in pulmonary arterial hypertension (PAH), a disease caused by mutation of bone morphogenetic protein receptor-2 (BMPR2). We demonstrated that SMURF1 inhibition prevented BMPR2 ubiquitylation, normalized bone morphogenetic protein (BMP) signaling, restored pulmonary vascular cell homeostasis, and reversed pathology in established experimental PAH. Leveraging this deep mechanistic understanding, we undertook an in silico machine-learning-based screen to identify inhibitors of the prototypic HECT E6AP and confirmed glycine-hinge-dependent allosteric activity in vitro. Inhibiting HECTs and other glycine-hinge proteins opens a new druggable space.

• MeSH
• Allosteric Regulation drug effects   MeSH
• Humans MeSH
• Mice MeSH
• Pulmonary Arterial Hypertension drug therapy   MeSH
• Bone Morphogenetic Protein Receptors, Type II MeSH
• Signal Transduction drug effects   MeSH
• Ubiquitination drug effects   MeSH
• Ubiquitin-Protein Ligases * antagonists & inhibitors   metabolism   chemistry   genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: This study develops a deep learning-based automated lesion segmentation model for whole-body 3D18F-fluorodeoxyglucose (FDG)-Position emission tomography (PET) with computed tomography (CT) images agnostic to disease location and site. METHOD: A publicly available lesion-annotated dataset of 1014 whole-body FDG-PET/CT images was used to train, validate, and test (70:10:20) eight configurations with 3D U-Net as the backbone architecture. The best-performing model on the test set was further evaluated on 3 different unseen cohorts consisting of osteosarcoma or neuroblastoma (OS cohort) (n = 13), pediatric solid tumors (ST cohort) (n = 14), and adult Pheochromocytoma/Paraganglioma (PHEO cohort) (n = 40). Both lesion-level and patient-level statistical analyses were conducted to validate the performance of the model on different cohorts. RESULTS: The best performing 3D full resolution nnUNet model achieved a lesion-level sensitivity and DISC of 71.70 % and 0.40 for the test set, 97.83 % and 0.73 for ST, 40.15 % and 0.36 for OS, and 78.37 % and 0.50 for the PHEO cohort. For the test set and PHEO cohort, the model has missed small volume and lower uptake lesions (p < 0.01), whereas no statistically significant differences (p > 0.05) were found in the false positive (FP) and false negative lesions volume and uptake for the OS and ST cohort. The predicted total lesion glycolysis is slightly higher than the ground truth because of FP calls, which experts can easily check and reject. CONCLUSION: The developed deep learning-based automated lesion segmentation AI model which utilizes 3D_FullRes configuration of the nnUNet framework showed promising and reliable performance for the whole-body FDG-PET/CT images.

• MeSH
• Whole Body Imaging * methods   MeSH
• Deep Learning * MeSH
• Child MeSH
• Adult MeSH
• Fluorodeoxyglucose F18 * MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Neoplasms * diagnostic imaging   MeSH
• Positron Emission Tomography Computed Tomography * methods   MeSH
• Image Processing, Computer-Assisted * methods   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH

Recent advances in protein 3D structure prediction using deep learning have focused on the importance of amino acid residue-residue connections (i.e., pairwise atomic contacts) for accuracy at the expense of mechanistic interpretability. Therefore, we decided to perform a series of analyses based on an alternative framework of residue-residue connections making primary use of the TOP2018 dataset. This framework of residue-residue connections is derived from amino acid residue pairing models both historic and new, all based on genetic principles complemented by relevant biophysical principles. Of these pairing models, three new models (named the GU, Transmuted and Shift pairing models) exhibit the highest observed-over-expected ratios and highest correlations in statistical analyses with various intra- and inter-chain datasets, in comparison to the remaining models. In addition, these new pairing models are universally frequent across different connection ranges, secondary structure connections, and protein sizes. Accordingly, following further statistical and other analyses described herein, we have come to a major conclusion that all three pairing models together could represent the basis of a universal proteomic code (second genetic code) sufficient, in and of itself, to "encode" for both protein folding mechanisms and protein-protein interactions.

• MeSH
• Amino Acids * chemistry   genetics   MeSH
• Databases, Protein MeSH
• Humans MeSH
• Models, Molecular * MeSH
• Proteins * chemistry   genetics   metabolism   MeSH
• Proteomics * MeSH
• Protein Folding * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH