Search

Abstract Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects ( > 3800x on-target index). Application of these ‘design rules’ to a distinct Mdm2(X) peptide series improves ( > 150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.

The article focuses on the diagnosis and clinical presentation of basal cell carcinoma (BCC) in a 68-year-old female patient. Topics include the typical characteristics of BCC, its association with sun exposure and other risk factors, and the importance of biopsy for diagnosis and distinguishing it from other skin cancers.

Over the past decade, with the support of Erasmus Mundus, the number of joint degree programmes in Europe has increased rapidly. In Asia, joint degree programmes have also gained popularity due to the growth of transnational higher education in the region since 2000. However, a joint degree programme is a highly complex and coordinated activity for the university partners involved. Cooperation and coordination are crucial for the quality of any joint degree programme. This study primarily explores QA approaches to European joint degree programmes and their current development in Asia.

Scant research has explored how the emotions of gift‐givers influence their gift selection, particularly negative emotions. Addressing this gap, this research examines how guilt impacts gift‐giving, capitalizing on the conceptual link between guilt, power, and size. Through four experiments, we demonstrate that, compared with gift‐givers in a control condition, guilty gift‐givers are more likely to choose conspicuously branded gifts—items with highly noticeable, large brand logos. We observe this effect using different scenarios and the autobiographical recall procedure to elicit guilt, as well as a variety of operationalizations of brand conspicuousness. We find that the sense of power and power restoration provided by the gift account for the results. Moreover, the preference for a conspicuously branded gift diminishes when guilty gift‐givers engage in reparative actions to alleviate their guilt prior to gift‐giving. This research contributes to the literature on guilt, power, and conspicuous consumption by revealing a novel consequence of guilt on consumer choice in gift‐giving contexts and expanding our understanding of conspicuous brand usage. The findings have practical implications for marketers, particularly in using guilt appeals and promoting conspicuously branded gifts. Finally, we suggest future research directions related to positive emotions and other outcomes of interest in gift‐giving. [ABSTRACT FROM AUTHOR]

The calcified chondroid mesenchymal neoplasm (CCMN) represents a recently recognized tumor type with only 50 well-documented cases in the English-language literature. Herein we report an additional case of CCMN presenting as a large mass in the temporomandibular joint region of a 41-year-old female. A review of previously reported cases and the current case of CCMN shows the following features: 1) average age 52 years (range 14–87 years) and an approximately even sex distribution; 2) most frequently involved sites: distal extremities (including foot, hand, wrist, forearm) (n=41) and temporomandibular joint/temporal/parotid region (n=9); 3) multilobular soft tissue tumor with chondroid to cartilaginous matrix, often grungy or lace-like calcifications, and variable cytologic atypia; 4) frequently detected FN1 rearrangement (n=15), including FN1 fusion with FGFR2 (n=7) or other receptor tyrosine kinases; 5) 2 reported local recurrences (after incomplete excision); 6) no reports of malignant biologic behavior. [ABSTRACT FROM AUTHOR]