Cedars-Sinai Medical Center

Rare-variant studies now yield more significant gene-phenotype associations than teams can place against prior evidence, and that placement has become the tighter bottleneck. PESTO combines large language model literature curation with structured Open Targets genetic evidence in one agentic pipeline that assigns Novel, Hypothesized, Existing or Established with supporting citations. Across 940 unique associations from two rare-variant studies, 7% were called Novel and 21% Hypothesized; 86% of 50 randomly paired negative controls fell into those two tiers.

Rare-variant studies now yield more significant gene-phenotype associations than teams can place against prior evidence, and that placement has become the tighter bottleneck. PESTO combines large language model literature curation with structured Open Targets genetic evidence in one agentic pipeline that assigns Novel, Hypothesized, Existing or Established with supporting citations. Across 940 unique associations from two rare-variant studies, 7% were called Novel and 21% Hypothesized; 86% of 50 randomly paired negative controls fell into those two tiers.

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.