Congenital myasthenic syndromes: increasingly complex DOI Creative Commons
Sithara Ramdas, David Beeson, Yin Yao Dong

et al.

Current Opinion in Neurology, Journal Year: 2024, Volume and Issue: 37(5), P. 493 - 501

Published: July 25, 2024

Purpose of review Congenital myasthenia syndromes (CMS) are treatable, inherited disorders affecting neuromuscular transmission. We highlight that the involvement an increasing number proteins is making understanding disease mechanisms and potential treatments progressively more complex. Recent findings Although early studies identified mutations directly involved in synaptic transmission at junction, recently, next-generation sequencing has facilitated identification many novel genes encode have a far wider expression profile, some even ubiquitously expressed, but whose defective function leads to impaired Unsurprisingly, these often causes phenotypic spectrum where forms only one component. This implications for management CMS patients. Summary Given widening nonneuromuscular junction phenotypes newly CMS, new therapies need include disease-modifying approaches address not weakness also multisystem involvement. Whilst current highly effective subtypes there remains, proportion patients, unmet efficacious therapies.

Language: Английский

Challenges and opportunities for digital twins in precision medicine from a complex systems perspective DOI Creative Commons
Manlio De Domenico,

Luca Allegri,

Guido Caldarelli

et al.

npj Digital Medicine, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 17, 2025

Digital twins (DTs) in precision medicine are increasingly viable, propelled by extensive data collection and advancements artificial intelligence (AI), alongside traditional biomedical methodologies. We argue that including mechanistic simulations produce behavior based on explicitly defined biological hypotheses multiscale mechanisms is beneficial. It enables the exploration of diverse therapeutic strategies supports dynamic clinical decision-making through insights from network science, quantitative biology, digital medicine.

Language: Английский

Citations

2
Lung Tissue Multi-Layer Network Analysis Uncovers the Molecular Heterogeneity of COPD DOI
Núria Olvera, Jon Sánchez-Valle, Iker Núñez‐Carpintero

et al.

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 210(10), P. 1219 - 1229

Published: April 16, 2024

Background. Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous condition. We hypothesized that the unbiased integration of different COPD lung omics using novel multi-layer approach may unravel mechanisms associated with clinical characteristics. Methods. profiled mRNA, miRNA and methylome in tissue samples from 135 former smokers COPD. For each omic (layer) we built patient network based on molecular similarity. The three networks were used to build network, optimization multiplex-modularity was employed identify communities across distinct layers. Uncovered related features. Results. identified five which molecularly characteristics, such as FEV1 blood eosinophils. Two (C#3 C#4) had both similarly low values emphysema, but different: C#3, not C#4, presented B T cell signatures downregulation secretory (SCGB1A1/SCGB3A1) ciliated cells. A machine learning model set up discriminate C#3 C#4 our cohort, validate them an independent cohort. Finally, spatial transcriptomics characterized small airway differences between identifying upregulation T/B homing chemokines, bacterial response genes C#3. Conclusions. analysis able clinically relevant communities. Patients emphysema can have airways immune patterns, indicating endotypes lead similar presentation.

Language: Английский

Citations

6
Blood biomarker fingerprints in a cohort of patients with CHRNE-related congenital myasthenic syndrome DOI Creative Commons
Adela Della Marina, Andrie Koutsoulidou, Daniel Natera‐de Benito

et al.

Acta Neuropathologica Communications, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 13, 2025

Language: Английский

Citations

0
Omics and rare diseases: challenges, applications, and future perspectives DOI
Daniela Braconi, Haidara Nadwa, Giulia Bernardini

et al.

Expert Review of Proteomics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

Introduction Rare diseases (RDs) are a heterogeneous group of recognized as relevant global health priority but posing aspects complexity such as: geographical scattering affected individuals, improper/late diagnosis, limited awareness, difficult surveillance and monitoring, understanding natural history, lack treatment. Usually, RDs have pediatric onset life-long, multisystemic, associated with poor prognosis.

Language: Английский

Citations

0
Characterization of Clinical Phenotypes in Congenital Myasthenic Syndrome Associated with the c.1327delG Frameshift Mutation in CHRNE Encoding the Acetylcholine Receptor Epsilon Subunit DOI
Kristina Kastreva, Teodora Chamova,

Stanislava Blagoeva

et al.

Journal of Neuromuscular Diseases, Journal Year: 2024, Volume and Issue: 11(5), P. 1011 - 1020

Published: July 12, 2024

Congenital myasthenic syndromes (CMS) are a group of rare but often treatable inherited disorders neuromuscular transmission characterized by fatigable skeletal muscle weakness. In this paper we present the largest phenotypic analysis to date cohort patients carrying pathogenic variant c.1327delG in CHRNE gene, leading CHRNE-CMS.

Language: Английский

Citations

3
Inter-alpha-trypsin inhibitor heavy chain H3 is a potential biomarker for disease activity in myasthenia gravis DOI Creative Commons
Christina B. Schroeter, Christopher Nelke, Frauke Stascheit

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)

Published: June 1, 2024

Abstract Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to stratify patients with active requiring intensified monitoring and therapy; their identification the primary objective of this study. We applied mass spectrometry-based proteomic serum profiling for biomarker discovery. studied exploration prospective validation cohort consisting 114 140 anti-acetylcholine receptor antibody (AChR-Ab)-positive myasthenia patients, respectively. For downstream analysis, we machine learning approach. Protein expression levels were confirmed by ELISA compared other myasthenic cohorts, in addition myositis neuropathy patients. Anti-AChR-Ab determined radio assay. Immunohistochemistry immunofluorescence intercostal muscle biopsies employed interactome studies inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3). Machine identified ITIH3 as potential reflective activity. Serum correlated activity scores ELISA. Lack correlation between anti-AChR-Ab clinical underlined biomarkers. In subgroup was indicative treatment responses. Immunostaining specimens from these demonstrated localization at endplates but not controls, thus providing structural equivalent our serological findings. Immunoprecipitation subsequent proteomics lead its interaction partners playing crucial roles This study provides data on pathophysiological-relevant gravis. Future are required facilitate translation into practice.

Language: Английский

Citations

2
Multilayer biological networks to upscale marine research to global change-smart management and sustainable resource use DOI
Diana Madeira,

Carolina Madeira,

Piero Calosi

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 944, P. 173837 - 173837

Published: June 12, 2024

Language: Английский

Citations

1
Congenital myasthenic syndromes: increasingly complex DOI Creative Commons
Sithara Ramdas, David Beeson, Yin Yao Dong

et al.

Current Opinion in Neurology, Journal Year: 2024, Volume and Issue: 37(5), P. 493 - 501

Published: July 25, 2024

Purpose of review Congenital myasthenia syndromes (CMS) are treatable, inherited disorders affecting neuromuscular transmission. We highlight that the involvement an increasing number proteins is making understanding disease mechanisms and potential treatments progressively more complex. Recent findings Although early studies identified mutations directly involved in synaptic transmission at junction, recently, next-generation sequencing has facilitated identification many novel genes encode have a far wider expression profile, some even ubiquitously expressed, but whose defective function leads to impaired Unsurprisingly, these often causes phenotypic spectrum where forms only one component. This implications for management CMS patients. Summary Given widening nonneuromuscular junction phenotypes newly CMS, new therapies need include disease-modifying approaches address not weakness also multisystem involvement. Whilst current highly effective subtypes there remains, proportion patients, unmet efficacious therapies.

Language: Английский

Citations

1