Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones

High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations. Visium spatial transcriptomics reveals multiple tumour subclones with different copy number alterations present within individual tumour sections. These subclones differentially express various ligands and receptors and are predicted to differentially associate with different stromal and immune cell populations. In one sample, CosMx single molecule imaging reveals subclones differentially associating with immune cell populations, fibroblasts, and endothelial cells. Cell-to-cell communication analysis identifies subclone-specific signalling to stromal and immune cells and multiple subclone-specific autocrine loops. Our study highlights the high degree of subclonal heterogeneity in HGSOC and suggests that subclone-specific ligand and receptor expression patterns likely modulate how HGSOC cells interact with their local microenvironment

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Ester prodrugs of flurbiprofen: Synthesis, plasma hydrolysis and gastrointestinal toxicity

1164-1168Nine alkyl ester prodrugs of flurbiprofen have been synthesized with an aim to reduce it’s gastrointestinal side-effects. The synthesized prodrugs have been subjected to plasma hydrolysis and gastrointestinal toxicity studies. The chemical structures of the prodrugs have been varied in terms of lipophilicity and reactivity towards hydrolysis. The plasma hydrolysis studies indicate that methyl and propyl prodrugs of flurbiprofen undergo faster hydrolysis as compared to the remaining ester prodrugs. Reduction of ulcer index in rats indicate that n-propyl, iso-propyl, benzyl and cyclopentyl prodrugs of flurbiprofen are significantly (p< 0.05) less irritating to the gastric mucosa as compared to the parent drug, i.e., flurbiprofen

Planning, Calibration and Collision-Avoidance for Image-Guided Radiosurgery

In radiosurgery a moving beam of radiation is used as an ablative surgical instrument to destroy brain tu-mors. Classical radiosurgical systems rely on rigid skeletal xation of the anatomic region to be treated. This xation procedure is very painful for the patient and limits radiosur-gical procedures to brain lesions. Furthermore, due to the necessity of rigid xation, radiosurgical treatment with clas-sical systems cannot be fractionated. A new camera-guided system capable of tracking patient motion during treatment has been built to overcome these problems. The radiation source is moved by a six degree-of-freedom robotic arm. In addition to o ering a more cost e ective, less invasive, and less painful treatment, the robotic gantry allows for arbitrary spatial motion of the radiation source. Based on this feature we can treat non-spherical lesions with accuracies unachiev-able with classical radiosurgical systems. The system intro-duces a new class of radiosurgical procedures, called non-stereotactic, orimage-guided radiosurgery. At the heart of these procedures are algorithms for planning both a treat-ment and the corresponding beam motion, given the geo-metric description of the tumor shape and relative locations in the particular case

Retrometabolism based drug targeting- Soft drug approach

721-733Despite considerable progress in medicinal chemistry in the last century, rational drug design that allows the development of effective pharmaceutical agents with minimal side effects is still an elusive goal. The primary causes for side effects are the generalized effect of drug on receptors present throughout the body and uncontrolled drug metabolism. Thus, it has become evident that targeting and metabolism considerations should be an integral part of any drug design process and that the focus should be on increasing activity as well as therapeutic index of the potential drug candidate. Various ideas have been suggested over the years to come up with an ideal approach to drug design. In this review, we shall be dealing with one such approach, that is, the soft drug approach. A soft drug is pharmacologically active as such, and it undergoes a predictable and controllable metabolism to nontoxic and inactive metabolites. The main concept of soft drug design is to avoid oxidative metabolism as much as possible and to use hydrolytic enzymes to achieve predictable and controllable drug metabolism. The discussion shall present an overview on the need for the development of soft drugs, associated terminologies and the different classes of soft drugs

Defining human-centricity in Industry 5.0 and assessing the readiness of Ergonomics/Human Factors communities in UK

There is a lack of a clear and consistent definition of human-centricity in Industry 5.0. This study identified the definition of human-centricity in Industry 5.0 through a systematic literature review and used it to assess the readiness of Ergonomics/Human Factors communities in the UK. The assessment of the communities readiness was conducted by reviewing UK accredited courses and events of three professional bodies; and interviewing practitioners (n=8). Eleven themes were identified as elements of human-centricity from the thematic analysis of 30 publications. Gaps that had to be addressed to better equip UK practitioners to support the realisation of human-centricity in Industry 5.0 were also identified

An update on developments in medical education in response to the COVID-19 pandemic: A BEME scoping review: BEME Guide No. 64

Background COVID-19 has fundamentally altered how education is delivered. Gordon et al. previously conducted a review of medical education developments in response to COVID-19; however, the field has rapidly evolved in the ensuing months. This scoping review aims to map the extent, range and nature of subsequent developments, summarizing the expanding evidence base and identifying areas for future research. Methods The authors followed the five stages of a scoping review outlined by Arskey and O’Malley. Four online databases and MedEdPublish were searched. Two authors independently screened titles, abstracts and full texts. Included articles described developments in medical education deployed in response to COVID-19 and reported outcomes. Data extraction was completed by two authors and synthesized into a variety of maps and charts. Results One hundred twenty-seven articles were included: 104 were from North America, Asia and Europe; 51 were undergraduate, 41 graduate, 22 continuing medical education, and 13 mixed; 35 were implemented by universities, 75 by academic hospitals, and 17 by organizations or collaborations. The focus of developments included pivoting to online learning (n = 58), simulation (n = 24), assessment (n = 11), well-being (n = 8), telehealth (n = 5), clinical service reconfigurations (n = 4), interviews (n = 4), service provision (n = 2), faculty development (n = 2) and other (n = 9). The most common Kirkpatrick outcome reported was Level 1, however, a number of studies reported 2a or 2b. A few described Levels 3, 4a, 4b or other outcomes (e.g. quality improvement)

An update on developments in medical education in response to the COVID-19 pandemic: A BEME scoping review: BEME Guide No. 64

Background: COVID-19 has fundamentally altered how education is delivered. Gordon et al. previously conducted a review of medical education developments in response to COVID-19; however, the field has rapidly evolved in the ensuing months. This scoping review aims to map the extent, range and nature of subsequent developments, summarizing the expanding evidence base and identifying areas for future research. Methods: The authors followed the five stages of a scoping review outlined by Arskey and O’Malley. Four online databases and MedEdPublish were searched. Two authors independently screened titles, abstracts and full texts. Included articles described developments in medical education deployed in response to COVID-19 and reported outcomes. Data extraction was completed by two authors and synthesized into a variety of maps and charts. Results: One hundred twenty-seven articles were included: 104 were from North America, Asia and Europe; 51 were undergraduate, 41 graduate, 22 continuing medical education, and 13 mixed; 35 were implemented by universities, 75 by academic hospitals, and 17 by organizations or collaborations. The focus of developments included pivoting to online learning (n = 58), simulation (n = 24), assessment (n = 11), well-being (n = 8), telehealth (n = 5), clinical service reconfigurations (n = 4), interviews (n = 4), service provision (n = 2), faculty development (n = 2) and other (n = 9). The most common Kirkpatrick outcome reported was Level 1, however, a number of studies reported 2a or 2b. A few described Levels 3, 4a, 4b or other outcomes (e.g. quality improvement). Conclusions: This scoping review mapped the available literature on developments in medical education in response to COVID-19, summarizing developments and outcomes to serve as a guide for future work. The review highlighted areas of relative strength, as well as several gaps. Numerous articles have been written about remote learning and simulation and these areas are ripe for full systematic reviews. Telehealth, interviews and faculty development were lacking and need urgent attention