The Well-Being of a University: The Relationship Between Gratitude and Organizational Commitment on Faculty Members’ Intention to Stay

Retaining good employees can be difficult, and no organization is immune. This study investigated the relationship between gratitude and organizational commitment to determine if they can predict the intention to stay among university faculty. Specifically, this study analyzed gratitude, a construct that has not been researched much in the workplace. There was a significant relationship between gratitude on organizational commitment. Gratitude and organizational commitment were important predictors of intention to stay. Gratitude was supported as a moderator between organizational commitment and intention to stay. Organizations should incorporate positive reinforcements to express gratitude to increase organizational commitment and intent to stay

Entrepreneurs’ Courage, Psychological Capital, and Life Satisfaction

Entrepreneurship involves numerous risks and uncertainties. Positive psychological resources such as courage, as well as confidence, hope, optimism, and resilience (collectively referred to as psychological capital), can be valuable for entrepreneurs. This study examines that relationship between entrepreneurs’ courage, psychological capital, and life satisfaction. Results show that entrepreneurs’ courage is related to their life satisfaction, even after accounting for various characteristics of the entrepreneur (demographics and human capital) and the venture (venture size and survival). Moreover, psychological capital fully mediates the relationship between courage and life satisfaction. This is the first study to investigate courage empirically in the context of entrepreneurship, and one of a few studies to apply PsyCap in the entrepreneurial context. It is also the first study to jointly examine courage, PsyCap, and life satisfaction. Implications for future research and practice are discussed

1O Safety, pharmacokinetics, efficacy, and biomarker results of SRK-181 (a latent TGFβ1 inhibitor) from a phase I trial (DRAGON trial)

Background: SRK-181 is an investigational, fully human, IgG4 monoclonal antibody that selectively binds to latent transforming growth factor-beta 1 (TGFβ1). TGFβ1 activation has been associated with primary resistance to PD-1/PD-L1 [PD-(L)1] blockade. Compared to broad TGFβ inhibitors, SRK-181 was observed to have an improved safety profile (no cardiotoxicities) in 4-week GLP toxicology studies. Methods: NCT04291079 is a multicenter ongoing phase I study with a 3+3 dose escalation design to evaluate SRK-181 in patients (pts) with advanced solid tumors at 80-3000mg q3w and 2000mg q2w (Part A1), and SRK-181 + anti-PD-(L)1 in pts with no response to prior anti-PD-(L)1 therapy at 240-2400mg q3w (Part A2). In Part B, SRK-181 (1500mg q3w or 1000mg q2w) + anti-PD-(L)1 are expanded in anti-PD-(L)1-resistant pts with non-small cell lung cancer, urothelial carcinoma, melanoma, clear cell renal cell carcinoma (ccRCC), or other advanced solid tumors. Results: As of Dec 2, 2022, the study enrolled 19 pts in Part A1 and 15 in Part A2 with no DLTs observed. The median prior lines of therapies were 4 (range 1-10). In Part A1, the most common treatment-related AEs (TRAEs, \u3e10%) of any grade were fatigue (16%, n=3), decreased appetite and nausea (each 11%, n=2). Best response of stable disease (SD) was observed in 8 pts. All 3 ovarian cancer pts were stable for 25 to 42 weeks. In Part A2, the TRAEs (\u3e10%) of any grade were rash maculo-papular (33%, n=5), pruritus (27%, n=4), rash (20%, n=3), diarrhea and pemphigoid (each 13%, n=2). One confirmed RECIST 1.1 partial response (cPR) was observed at 800mg in a pt with anti-PD-1 resistant ccRCC who stayed on study for 30 weeks. Of 9 pts with best response of SD, 5 were stable \u3e16 weeks. SRK-181 treatment resulted in increased levels of circulatory TGFβ1, indicating target engagement. Part B enrollment is ongoing (N=9 in ccRCC cohort); two cPR were observed in pts with anti-PD-1 resistant ccRCC. Conclusions: SRK-181 has been tolerated as monotherapy and in combination with anti-PD-(L)1. No DLTs were observed up to 3000mg q3w/2000mg q2w as monotherapy and up to 2400mg q3w as combination treatment. Early signs of efficacy were observed with 3 cPR in pts with anti-PD-1 resistant ccRCC

PDX-derived organoids model in vivo drug response and secrete biomarkers

Patient-derived organoid models are proving to be a powerful platform for both basic and translational studies. Here we conduct a methodical analysis of pancreatic ductal adenocarcinoma (PDAC) tumor organoid drug response in paired patient-derived xenograft (PDX) and PDX-derived organoid (PXO) models grown under WNT-free culture conditions. We report a specific relationship between area under the curve value of organoid drug dose response and in vivo tumor growth, irrespective of the drug treatment. In addition, we analyzed the glycome of PDX and PXO models and demonstrate that PXOs recapitulate the in vivo glycan landscape. In addition, we identify a core set of 57 N-glycans detected in all 10 models that represent 50%–94% of the relative abundance of all N-glycans detected in each of the models. Last, we developed a secreted biomarker discovery pipeline using media supernatant of organoid cultures and identified potentially new extracellular vesicle (EV) protein markers. We validated our findings using plasma samples from patients with PDAC, benign gastrointestinal diseases, and chronic pancreatitis and discovered that 4 EV proteins are potential circulating biomarkers for PDAC. Thus, we demonstrate the utility of organoid cultures to not only model in vivo drug responses but also serve as a powerful platform for discovering clinically actionable serologic biomarkers