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The article discusses three phase 3 clinical trials presented at the European Society for Medical Oncology Congress 2023, demonstrating the superiority of targeted therapies over conventional chemotherapy in patients with oncogene-addicted non–small cell lung cancer (NSCLC). The trials focused on alectinib for ALK-positive NSCLC, amivantamab for EGFR exon 20 insertion–mutated NSCLC, and selpercatinib for advanced or metastatic RET mutation–positive medullary thyroid cance.

The article discusses the results of the phase 3 CheckMate 77T clinical trial, which evaluated a perioperative regimen of neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab in patients with resectable non–small cell lung cancer (NSCLC). The study demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS) compared to neoadjuvant chemotherapy plus placebo.

The unfolded protein response (UPR) is sensitive to proteotoxic and membrane bilayer stress, both of which are sensed by the ER protein Ire1. When activated, Ire1 splices HAC1 mRNA, producing a transcription factor that targets genes involved in proteostasis and lipid metabolism, among others. The major membrane lipid phosphatidylcholine (PC) is subject to phospholipase-mediated deacylation, producing glycerophosphocholine (GPC), followed by reacylation of GPC through the PC deacylation/reacylation pathway (PC-DRP). The reacylation events occur via a two-step process catalyzed first by the GPC acyltransferase Gpc1, followed by acylation of the lyso-PC molecule by Ale1. However, whether Gpc1 is critical for ER bilayer homeostasis is unclear. Using an improved method for C14-choline-GPC radiolabeling, we first show that loss of Gpc1 results in abrogation of PC synthesis through PC-DRP and that Gpc1 colocalizes with the ER. We then probe the role of Gpc1 as both a target and an effector of the UPR. Exposure to the UPR-inducing compounds tunicamycin, DTT, and canavanine results in a Hac1-dependent increase in GPC1 message. Further, cells lacking Gpc1 exhibit increased sensitivity to those proteotoxic stressors. Inositol limitation, known to induce the UPR via bilayer stress, also induces GPC1 expression. Finally, we show that loss of GPC1 induces the UPR. A gpc1? mutant displays upregulation of the UPR in strains expressing a mutant form of Ire1 that is unresponsive to unfolded proteins, indicating that bilayer stress is responsible for the observed upregulation. Collectively, our data indicate an important role for Gpc1 in yeast ER bilayer homeostasis. [ABSTRACT FROM AUTHOR]

This article examines how a faculty member's status--either tenured or tenure-track--might affect the grades assigned to students in a writing class. We begin with a brief review of the research surrounding faculty to student assessment practices and follow with specific controversies regarding faculty motivation pertaining to grading practices. We interpret the grade distributions of tenured and tenure-track faculty members teaching a sophomore-level writing course in an English Department at a small, public liberal arts university in Virginia, examine the relationship between grade distributions and faculty rank, and conclude that tenure-track faculty grade more leniently than their tenured colleagues, primarily in the number of "A" grades assigned. The results of this study suggest that tenured professors tend to award fewer "As" than tenure-track professors. We posit that at universities where emphasis is placed upon teaching, two specific patterns emerge: reciprocity may be an unspoken agreement between some faculty and students with regard to the exchange of good grades for good evaluations, or with experience comes rigor. (Contains 1 figure and 1 table.)