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The COVID-19 pandemic forced UK universities to move the majority or all of tuition online. The Library Academic Support Team at Leeds Beckett University used that shift as an opportunity to improve information literacy (IL) and academic skills tuition across the institution. Instruction and support were redesigned on a flipped basis to ensure that online delivery improved on face-to-face delivery rather than simply replicating it. This project report reviews that work with usage statistics, user feedback, practicalities of service provision and discussion of impact. The report extends existing literature with a model of significant institution-level changes to IL and academic skills instruction which could be applied elsewhere. It concludes that the shift to flipped online learning was a qualified success, with the revised approach proving notably more popular and inclusive, also providing other benefits such as more focused in-class discussion.

This case study examines the introduction of a centrally managed booking system for academic skills appointments conducted by the Library Academic Support Team at Leeds Beckett University, showing how staff-student communication channels can scaffold effective student support. The new system was introduced in order to manage a large number of requests for skills appointments across all academic levels, to ensure an equitable experience for all learners, and to frame staff-student encounters more effectively at the formative stage. Further benefits included provision of more focused tuition, additional data on learner requirements, greater capacity to re-route appointment requests, and more efficient use of student and staff time, while retaining the option of human intervention in the system as required. This paper demonstrates a transferrable means of enhancing institutional processes whilst retaining the traditional strengths of one-to-one encounters in order to improve the overall student experience.

Inhibition of the Menin (MEN1) and MLL (MLL1, KMT2A) interaction is a potential therapeutic strategy for MLL-rearranged (MLL-r) leukemia. Structure-based design yielded the potent, highly selective, and orally bioavailable small-molecule inhibitor VTP50469. Cell lines carrying MLL rearrangements were selectively responsive to VTP50469. VTP50469 displaced Menin from protein complexes and inhibited chromatin occupancy of MLL at select genes. Loss of MLL binding led to changes in gene expression, differentiation, and apoptosis. Patient-derived xenograft (PDX) models derived from patients with either MLL-r acute myeloid leukemia or MLL-r acute lymphoblastic leukemia (ALL) showed dramatic reductions of leukemia burden when treated with VTP50469. Multiple mice engrafted with MLL-r ALL remained disease free for more than 1 year after treatment. These data support rapid translation of this approach to clinical trials.

Purpose: OBI-3424 is a highly selective prodrug that is OBI-3424 significantly prolonged the event-free survival (EFS) converted by aldo-keto reductase family 1 member C3 of nine of nine ALL PDXs by 17.1–77.8 days (treated/control (AKR1C3) to a potent DNA-alkylating agent. OBI-3424 has values 2.5–14.0), and disease regression was observed in eight entered clinical testing for hepatocellular carcinoma and cas-of nine PDXs. A significant reduction (P < 0.0001) in bone trate-resistant prostate cancer, and it represents a potentially marrow infiltration at day 28 was observed in four of six novel treatment for acute lymphoblastic leukemia (ALL). evaluable T-ALL PDXs. The importance of AKR1C3 in the Experimental Design: We assessed AKR1C3 expression by in vivo response to OBI-3424 was verified using a B-ALL PDX RNA-Seq and immunoblotting, and evaluated the in vitro that had been lentivirally transduced to stably overexpress cytotoxicity of OBI-3424. We investigated the pharmacokinet-AKR1C3. OBI-3424 combined with nelarabine resulted in ics of OBI-3424 in mice and nonhuman primates, and assessed prolongation of mouse EFS compared with each single agent the in vivo efficacy of OBI-3424 against a large panel of patient-alone in two T-ALL PDXs. derived xenografts (PDX). Conclusions: OBI-3424 exerted profound in vivo efficacy Results: AKR1C3 mRNA expression was significantly higher against T-ALL PDXs derived predominantly from aggressive in primary T-lineage ALL (T-ALL; n ¼ 264) than B-lineage and fatal disease, and therefore may represent a novel treat-ALL (B-ALL; n ¼ 1,740; P < 0.0001), and OBI-3424 exerted ment for aggressive and chemoresistant T-ALL in an AKR1C3 potent cytotoxicity against T-ALL cell lines and PDXs. In vivo, biomarker-driven clinical trial.