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1.
Front Neurol ; 14: 1195923, 2023.
Article in English | MEDLINE | ID: mdl-37333009

ABSTRACT

Introduction: Chronic pain is a multifaceted condition that has yet to be fully comprehended. It is frequently linked with a range of disorders, particularly osteoarthritis (OA), which arises from the progressive deterioration of the protective cartilage that cushions the bone endings over time. Methods: In this paper, we examine the impact of chronic pain on the brain using advanced deep learning (DL) algorithms that leverage resting-state functional magnetic resonance imaging (fMRI) data from both OA pain patients and healthy controls. Our study encompasses fMRI data from 51 pain patients and 20 healthy subjects. To differentiate chronic pain-affected OA patients from healthy controls, we introduce a DL-based computer-aided diagnosis framework that incorporates Multi-Layer Perceptron and Convolutional Neural Networks (CNN), separately. Results: Among the examined algorithms, we discovered that CNN outperformed the others and achieved a notable accuracy rate of nearly 85%. In addition, our investigation scrutinized the brain regions affected by chronic pain and successfully identified several regions that have not been mentioned in previous literature, including the occipital lobe, the superior frontal gyrus, the cuneus, the middle occipital gyrus, and the culmen. Discussion: This pioneering study explores the applicability of DL algorithms in pinpointing the differentiating brain regions in OA patients who experience chronic pain. The outcomes of our research could make a significant contribution to medical research on OA pain patients and facilitate fMRI-based pain recognition, ultimately leading to enhanced clinical intervention for chronic pain patients.

2.
Cell Rep Med ; 4(5): 101036, 2023 05 16.
Article in English | MEDLINE | ID: mdl-37196635

ABSTRACT

Genetic and in vivo evidence suggests that aberrant recognition of RNA-containing autoantigens by Toll-like receptors (TLRs) 7 and 8 drives autoimmune diseases. Here we report on the preclinical characterization of MHV370, a selective oral TLR7/8 inhibitor. In vitro, MHV370 inhibits TLR7/8-dependent production of cytokines in human and mouse cells, notably interferon-α, a clinically validated driver of autoimmune diseases. Moreover, MHV370 abrogates B cell, plasmacytoid dendritic cell, monocyte, and neutrophil responses downstream of TLR7/8. In vivo, prophylactic or therapeutic administration of MHV370 blocks secretion of TLR7 responses, including cytokine secretion, B cell activation, and gene expression of, e.g., interferon-stimulated genes. In the NZB/W F1 mouse model of lupus, MHV370 halts disease. Unlike hydroxychloroquine, MHV370 potently blocks interferon responses triggered by specific immune complexes from systemic lupus erythematosus patient sera, suggesting differentiation from clinical standard of care. These data support advancement of MHV370 to an ongoing phase 2 clinical trial.


Subject(s)
Autoimmune Diseases , Lupus Erythematosus, Systemic , Humans , Mice , Animals , Toll-Like Receptor 7/metabolism , Toll-Like Receptor 7/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/metabolism , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Interferons
3.
Praxis (Bern 1994) ; 110(2): 105-107, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33530775

ABSTRACT

In adults, an isolated non-traumatic fracture of the lesser trochanter should arouse strong suspicion of an underlying malignant pathology. In this article, we present the case of a 55-year-old male patient who presented with a non-traumatic isolated fracture of the lesser trochanter secondary to a delayed diagnosis of metastases of bronchial carcinoma.


Subject(s)
Fractures, Avulsion , Hip Fractures , Adult , Femur , Hip Fractures/diagnostic imaging , Hip Fractures/surgery , Humans , Male , Middle Aged
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