Accelerated enzyme engineering by machine-learning guided cell-free expression.

Enzyme engineering is limited by the challenge of rapidly generating and using large datasets of sequence-function relationships for predictive design. To address this challenge, we develop a machine learning (ML)-guided platform that integrates cell-free DNA assembly, cell-free gene expression, and functional assays to rapidly map fitness landscapes across protein sequence space and optimize enzymes for multiple, distinct chemical reactions. We apply this platform to engineer amide synthetases by evaluating substrate preference for 1217 enzyme variants in 10,953 unique reactions.

Quality of life outcomes in patients participating in the CALGB 30610 trial (CALGB 70702): Alliance.

Background: CALGB 30610 trial demonstrated that once daily thoracic radiotherapy (TRT) was not superior compared to standard twice daily TRT, in patients with limited stage small cell lung cancer. Quality of life outcomes may help oncologists decide the best treatment approach.

Methods: A total of 417 patients on CALGB 30610 participated in the quality-of-life substudy (CALGB 70702), which included the FACT Trial Outcome Index-Lung Cancer (FACT-L TOI), FACT-Esophageal Cancer (FACT-E) Eating and Swallowing Indices, ECOG Acute Esophagitis Scale, Hospital Anxiety and Depression Scale (HADS), difficulty swallowing, EQ-5D, and treatment convenience assessment at baseline, 3, 5, 7, 12, 26, and 52 weeks after starting TRT.

Prognostic Factors in Limited-Stage Small Cell Lung Cancer: A Secondary Analysis of CALGB 30610-RTOG 0538.

Importance: The impact of patient-specific, disease-related, and social factors on outcomes in limited-stage small cell lung cancer (LS-SCLC) is not well defined. A post hoc secondary analysis of such factors from the Cancer and Leukemia Group B (CALGB) 30610-Radiation Therapy Oncology Group (RTOG) 0538 trial may impact future trial design.

Objective: To assess the comprehensive demographic, disease-related, treatment-related, and social factors for potential associations with survival outcomes and understand whether specific subpopulations may benefit from radiotherapy (RT) dose escalation in LS-SCLC.

Substance Use Disorder as Risk Factor for Intubation in Angioedema: A Nationwide Cohort Study.

Objectives: Individuals with angioedema (AE) are at high risk for airway compromise and often require endotracheal intubation. Patient factors predisposing one to airway compromise are not well described. The objective of this study is to examine whether substance use disorder (SUD) in patients with AE is associated with need for airway intervention.

Long-Term Prospective Outcomes of Intensity Modulated Radiotherapy for Locally Advanced Lung Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The optimal radiotherapy technique for unresectable locally advanced non-small cell lung cancer (NSCLC) is controversial, so evaluating long-term prospective outcomes of intensity-modulated radiotherapy (IMRT) is important.

Objective: To compare long-term prospective outcomes of patients receiving IMRT and 3-dimensional conformal radiotherapy (3D-CRT) with concurrent carboplatin/paclitaxel for locally advanced NSCLC.

Design, Setting, And Participants: A secondary analysis of a prospective phase 3 randomized clinical trial NRG Oncology-RTOG 0617 assessed 483 patients receiving chemoradiotherapy (3D-CRT vs IMRT) for locally advanced NSCLC based on stratification.