University of Colorado Anschutz

A four-metabolite urine and plasma panel separated cancer cases from controls across eight cancer types, and a model that never used outcome labels still reached an AUC of 0.925 against 0.991 for supervised learning.

A four-metabolite urine and plasma panel separated cancer cases from controls across eight cancer types, and a model that never used outcome labels still reached an AUC of 0.925 against 0.991 for supervised learning.

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.

Using DEFT, an LLM-guided interpretable decision-tree framework, the authors found that pause sites are discriminated by a G at the pause position, C or T at +1 and a minimum G content in the 49 upstream bases (held-out AUROC 0.92, accuracy 0.87); inserting a 377 bp G-less cassette at the 5' ends of NDRG1 and HSP90AA1 abolished the promoter-proximal pause in an orientation-dependent way without impairing hypoxic or heat-shock activation (NDRG1 was even super-activated), while ChIP 5' RNAPII, Ser5P and NELF peaks persisted without NET-seq-detectable pausing and CTD deletion weakened the pause and shifted its peak from ~+80 to ~+40, supporting a model in which the pause is initiated by G-dependent arrest and stabilized by factors including CTD-mediated tethering.

Using DEFT, an LLM-guided interpretable decision-tree framework, the authors found that pause sites are discriminated by a G at the pause position, C or T at +1 and a minimum G content in the 49 upstream bases (held-out AUROC 0.92, accuracy 0.87); inserting a 377 bp G-less cassette at the 5' ends of NDRG1 and HSP90AA1 abolished the promoter-proximal pause in an orientation-dependent way without impairing hypoxic or heat-shock activation (NDRG1 was even super-activated), while ChIP 5' RNAPII, Ser5P and NELF peaks persisted without NET-seq-detectable pausing and CTD deletion weakened the pause and shifted its peak from ~+80 to ~+40, supporting a model in which the pause is initiated by G-dependent arrest and stabilized by factors including CTD-mediated tethering.