We show that α-mannosidase activity decreases with TNFα treatment in endothelial cells, and this decrease correlates with HM N-glycan formation on the cell surface. Further, we demonstrate that this inhibition is class-I dependent, and is independent of NF-κB upregulation of ICAM-1. Finally, we show that this inhibition is due in part to hydrogen peroxide (H2O2), generated by Endoplasmic Reticulum oxidoreductase 1-α (ERO1α). These data provide insights into the regulation of surface N-glycans during inflammation and demonstrate a novel role for reactive species in N-glycan biosynthesis. V.INTRODUCTION Programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) is the primary clinically-available biomarker of response to immunotherapy in non-small cell lung cancer (NSCLC), but factors associated with PD-L1 expression are not well understood. METHODS Consecutive nonsquamous NSCLCs with successful PD-L1 assessment and targeted next-generation sequencing (NGS) were included in this retrospective study. Clinicopathological characteristics, gene mutations, and copy number changes in gene and chromosomal arms were compared among three PD-L1 expression groups negative (TPS less then 1%), low (TPS 1-49%), and high (TPS ≥50%). A Q-value less then 0.25 was considered significant after multiple comparisons correction. RESULTS A total of 909 nonsquamous NSCLCs were included. High PD-L1 expression compared to low and negative PD-L1 expression was associated with increased tobacco exposure (median pack-years 25 vs. 20 vs. 20, respectively; P=0.01), advanced stage at diagnosis (76% vs. 67% vs. 61% w002) on immunotherapy. CONCLUSIONS PD-L1 expression is associated with specific genomic alterations and clinicopathologic characteristics in nonsquamous NSCLC. OBJECTIVE The objective of this study was to compare the effects of cognitive load and surgical performance in medical students that performed the open inguinal hernia repair after preparation with step-by-step video-demonstration versus continuous video-demonstration. Hypothetically, the step-by-step group will perceive lower extraneous load during the preparation of the surgical procedure compared to the continuous group. Subsequently, fewer errors will be made in the surgical performance assessment by the step-by-step group, resulting in better surgical performance. DESIGN In this prospective study, participants were randomly assigned to the step-by-step or continuous video-demonstration. They completed questionnaires regarding perceived cognitive load during preparation (10-point Likert scale). Their surgical performance was assessed on a simulation hernia model using the Observational Clinical Human Reliability Assessment. SETTING Erasmus University Medical Center, Rotterdam, the Netherlands. PARTICIPANTS Participants included medical students who were enrolled in extracurricular anatomy courses. RESULTS Forty-three students participated; 23 students in the step-by-step group and 20 in the continuous group. As expected, the step-by-step group perceived a lower extraneous cognitive load (2.92 ± 1.21) compared to the continuous group (3.91 ± 1.67, p = 0.030). The surgical performance was not statistically significantly different between both groups; however, in subanalyses on a selection of students that prepared for 1 to 2 hours, the step-by-step group made less procedural errors, 1.67 ± 1.11, compared to the continuous group, 3.06 ± 1.91, p = 0.018. CONCLUSIONS Our results suggest that preparation using step-by-step video-based learning results in lower extraneous cognitive load and subsequently fewer procedural errors during the surgical performance. For learning purposes, demonstration videos of surgical procedures should be presented in a segmented format. OBJECTIVE There is growing interest in the problem of burnout among physicians. Here, we examine the factors associated with burnout in orthopedic surgical training. DESIGN An Internet-based anonymous survey assessing workload, work-life balance, education, and resident-specific factors such as marital status and postgraduate year was developed. The survey was distributed to United States orthopedic surgery residency directors in September 2018, and program directors were asked to forward the survey to their trainees. BafA1 Multivariable analysis assessed correlations with burnout. SETTING All 161 Accreditation Council for Graduate Medical Education (ACGME)-accredited United States orthopedic surgery residency programs. PARTICIPANTS Two hundred and three United States orthopedic surgery residents. RESULTS Thirty-eight percent of respondents reported symptoms of burnout. Even so, the vast majority did not regret choosing a medical career (95%) or their choice of residency program (90%). Greater than half of traineesality of care and decrease medical errors. BACKGROUND & AIMS We investigated whether ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) is involved in development of hepatocellular carcinoma (HCC). METHODS We analyzed clinical and gene expression data from The Cancer Genome Atlas. Albumin-Cre (HepWT) mice and mice with hepatocyte-specific disruption of Abl1 (HepAbl-/- mice) were given hydrodynamic injections of plasmids encoding the sleeping beauty transposase and transposons with the MET gene and a catenin beta 1 gene with an N-terminal truncation, which induces development of liver tumors. Some mice were then gavaged with the ABL1 inhibitor nilotinib or vehicle (control), daily for 4 weeks. We knocked down ABL1 with short hairpin RNAs in Hep3B and Huh7 HCC cells and analyzed their proliferation and growth as xenograft tumors in mice. We performed RNA sequencing and gene set enrichment analysis of tumors. We knocked down or overexpressed NOTCH1 and MYC in HCC cells and analyzed proliferation. We measured levels of phosphorylated ABL1, MYC, and of liver tumors in mice with MET and catenin beta 1 transposons, reducing tumor levels of MYC and NOTCH1. CONCLUSIONS HCC samples have increased levels of ABL1 compared with non-tumor liver tissues, and increased levels of ABL1 correlate with shorter survival times of patients. Loss or inhibition of ABL1 reduces proliferation of HCC cells and slows growth of liver tumors in mice. Inhibitors of ABL1 might be used for treatment of HCC.