University College Dublin

Isolated focal dystonia has fewer than five known causal genes, and small families with incomplete penetrance make linkage analysis hard. A 3D convolutional network, DystoniaGeneNet, judged familial status from T1-weighted brain MRI and correctly classified 18 of 21 independent familial cases (85.7%), then guided exome variant prioritization and segregation analysis in 214 individuals. Rare variants segregating with disease emerged in RAP1GAP, TNN and ITSN2, all converging on perisynaptic extracellular matrix–synapse signalling.

Isolated focal dystonia has fewer than five known causal genes, and small families with incomplete penetrance make linkage analysis hard. A 3D convolutional network, DystoniaGeneNet, judged familial status from T1-weighted brain MRI and correctly classified 18 of 21 independent familial cases (85.7%), then guided exome variant prioritization and segregation analysis in 214 individuals. Rare variants segregating with disease emerged in RAP1GAP, TNN and ITSN2, all converging on perisynaptic extracellular matrix–synapse signalling.

An international multidisciplinary working group of 41 experts systematically reviewed 922 citations up to March 17, 2025, revised the 2016 acute exacerbation (AE) definition—previously limited to idiopathic pulmonary fibrosis (IPF)—into an AE-fILD definition applicable across all fibrotic interstitial lung diseases (anchored in diffuse alveolar damage with or without organizing pneumonia), proposed the broader concept of acute respiratory worsening (ARW) to capture acute deteriorations not attributable to DAD, and summarized evidence on epidemiology, risk factors, prognosis, and management while discussing AE as a clinical trial endpoint.

An international multidisciplinary working group of 41 experts systematically reviewed 922 citations up to March 17, 2025, revised the 2016 acute exacerbation (AE) definition—previously limited to idiopathic pulmonary fibrosis (IPF)—into an AE-fILD definition applicable across all fibrotic interstitial lung diseases (anchored in diffuse alveolar damage with or without organizing pneumonia), proposed the broader concept of acute respiratory worsening (ARW) to capture acute deteriorations not attributable to DAD, and summarized evidence on epidemiology, risk factors, prognosis, and management while discussing AE as a clinical trial endpoint.