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Movin Peramuna Gamage,1 Ravanth Baskaran,1 Srinjay Mukhopadhyay,1 Nishaanth Dalavaye,1 Becky Leveridge,1 Sashiananthan Ganesananthan,2 Robert Spencer,3,4 Susruta Manivannan,5 Malik Zaben3,4 1School of Medicine, Cardiff University, Heath Park Campus, Cardiff, CF14 4YS, UK; 2Department of Digestion, Metabolism and Reproduction, Imperial College London, London, UK; 3Neuroscience and Mental Health Innovation Institute (NMHII), Cardiff University, Cardiff, UK; 4Department of Neurosurgery, University Hospital of Wales, Cardiff, UK; 5Division of Psychological Medicine and Clinical Neurosciences, University Hospital of Wales, Cardiff, UKCorrespondence: Malik Zaben, Department of Neurosurgery, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, UK, Tel +442920748153, Email ZabenM@cardiff.ac.ukPurpose: Objective Structured Clinical Examination (OSCE) is a vital examination that must be passed to graduate as a qualified doctor. The delivery of OSCE teaching was changed to an online format to accommodate COVID-19 restrictions. Therefore, this study evaluates factors that students perceive to affect their virtual learning of clinical skills for OSCE.Methods: In this cross-sectional study, all medical students from across the world who attended “The Respiratory Station” session delivered by OSCEazy (a medical student organization providing free online medical education) in the academic year 2020– 2021 received an online questionnaire about their perceptions of this learning opportunity. The survey was created on Google™ forms and consisted of 5-point Likert scales as well as free-text boxes.Results: A total of 556 responses were received (mean age: 24, female: 76.6%). Most students agreed that online OSCE teaching offers more flexibility and convenience (median: 5, IQR: 4– 5) but their likeliness to ask questions in either format was similar (median: 4, IQR: 3– 5 vs median: 4, IQR: 3– 4, p value: 0.94). The use of visual aids (median: 5, IQR: 4– 5) and breakout rooms (median: 3, IQR: 2– 4) were thought to enhance the quality of virtual OSCE teaching. The biggest concern about online teaching was access to a stable internet connection (69.1%).Conclusion: The flexibility and convenience of virtual OSCE teaching enables the sharing of knowledge and skills to a wider audience and thus may be a very useful adjunct to face-to-face OSCE teaching in the future.Keywords: medical education, COVID-19, online learning, student perceptions

Abstract Regulation of cell division is crucial for the development of multicellular organisms, and in plants, this is in part regulated by the D-type cyclins (CYCD) and cyclin-dependent kinase A (CDKA) complex. Cell division regulation in Physcomitrium differs from other plants, by having cell division checks at both the G1 to S and G2 to M transition, controlled by the CYCD1/CDKA2 and CYCD2/CDKA1 complexes, respectively. This led us to hypothesize that upregulation of cell division could be archived in Bryophytes, without the devastating phenotypes observed in Arabidopsis. Overexpressing lines of PpCYCD1, PpCYCD2, PpCDKA1, or PpCDKA2 under Ubiquitin promotor control provided transcriptomic and phenotypical data that confirmed their involvement in the G1 to S or G2 to M transition control. Interestingly, combinatorial overexpression of all four genes produced plants with dominant PpCDKA2 and PpCYCD1 phenotypes and led to plants with twice as large gametophores. No detrimental phenotypes were observed in this line and two of the major carbon sinks in plants, the cell wall and starch, were unaffected by the increased growth rate. These results show that the cell cycle characteristics of P. patens can be manipulated by the ectopic expression of cell cycle regulators.

Abstract Background Near-peer medical education serves as an important method of delivering education to junior students by senior students. Due to the reduced clinical exposure because of the COVID-19 pandemic, we developed a mentorship scheme to help medical students with their Integrated Structured Clinical Examinations (ISCEs) by providing a combination of near-peer mentorship together with lecture-based teaching on a weekly basis for a 12-week period. Students attended a specialty-focused lecture every Tuesday followed by a small group teaching session organised by their tutor. Methods A longitudinal evaluative interventional study was undertaken by the international student led medical education organisation, OSCEazy. The teaching programme was organised and conducted by third year medical students to a recruited cohort of second year medical students. Students’ perceptions of ISCEs (confidence, anxiety, and overall performance) were evaluated using 5-point Likert scales while their knowledge of the specialty was assessed using 10 single best answer questions which were distributed via Google® forms at the start and end of each week. In addition, we assessed tutor perceptions of their teaching and learning experience. Results Seventy-two tutees were enrolled in the programme (mean age: 24.4, female: 77.8%). 88.9% of the participants had not attended any online ISCE teaching prior to this. They preferred in-person ISCE teaching as compared to virtual sessions [median 4.5 (IQR 4–5) vs 3 (IQR 3–4), p

BackgroundThe potential of popular culture as a tool for knowledge delivery and enhancing engagement in education is promising but not extensively studied. Furthermore, concerns exist regarding learning fatigue due to increased reliance on videoconferencing platforms following the COVID-19 pandemic. To ensure effective web-based teaching sessions that maintain attention spans and enhance understanding, innovative solutions are necessary. ObjectiveThis study aims to evaluate the use of specific popular culture case studies to enhance student engagement in a web-based near-peer teaching session. MethodsWe delivered a web-based teaching session to undergraduate medical students in the United Kingdom. The session included clinical vignettes and single-best-answer questions using characters from “The Simpsons” television show as patient analogies for various causes of jaundice. A pre-post survey, employing a 7-point Likert scale, was distributed to gather data from participants. ResultsA total of 53 survey responses were collected. Participants reported significantly improved understanding of jaundice after the session compared to before the session (median 6, IQR 5-6 vs median 4, IQR 3-4.5; P

Objectives It is estimated that NHS staff consist of over 200 different nationalities, with a reported 30.7% of doctors holding a nationality other than British. Despite this, international medical students represent 7.5% of all medical students studying in the UK and pay on average, 4–6 times more in tuition fees when compared with the £9250 per annum (Great British Pounds (£) in 2021) paid by home students. This study’s aim and objective are to evaluate the perception of the financial cost and value of the UK medical degree for international students and their motivations for pursuing such a degree.Methods This is a cross-sectional observational study enquiring about international premedical, medical and medical school graduates’ perception of the value of the UK medical degree and factors influencing their decision to study in the UK.A questionnaire was developed and distributed to 24 medical schools and 64 secondary schools both internationally and across the UK.Results A total of 352 responses from 56 nationalities were recorded. 96% of international students identified clinical and academic opportunities as the most important factors to study medicine in the UK, closely followed by quality of life (88%). The least important factor was family reasons, with 39% of individuals identifying this factor. Only 4.82% of graduates in our study considered leaving the UK after training. Overall, 54% of students felt the UK degree was value for money. This belief was significantly higher in premedical students compared with existing students and graduates (71% vs 52% and 20%, p

Srinjay Mukhopadhyay,1 Ravanth Baskaran,1 Movin Peramuna Gamage,1 Nishaanth Dalavaye,1 Wing Sum Vincent Ng,1 Sripradha Srinivasan,1 Sashiananthan Ganesananthan,2 Stephen Rutherford3 1School of Medicine, Cardiff University, Cardiff, UK; 2Department of Digestion, Metabolism and Reproduction, Imperial College London, London, UK; 3School of Biosciences, Cardiff University, Cardiff, UKCorrespondence: Sashiananthan Ganesananthan, Department of Digestion, Metabolism and Reproduction, Imperial College London, London, SW7 2AZ, UK, Email sashiganes96@yahoo.co.ukPurpose: The COVID-19 pandemic caused significant disruption to higher education, including medical studies. Online learner support became urgently necessary, and peer-support of learning was needed to supplement formal teaching. This study evaluates the impact and delivery media of OSCEazy, a student-led initiative supporting formal teaching across institutional and national boundaries.Methods: A survey was created on Google Forms and disseminated via the Zoom chat function to all the participants at the end of our event titled, “The Cardiology Station”.Results: A large proportion (99.5%) of the students have a Facebook account and (98.7%) use it to keep track of medical events (p=0.45 for comparison). However, a very small proportion of use their other social media to keep up with medical events (p< 0.0001 for comparison).Conclusion: It is evident from our results, that most of our participants used Facebook to keep track of medical events. The use of their other social media platforms (Instagram, etc) to keep track of medical events was limited. Thus, it is important for any organisation, such as ours, who conduct online events to evaluate which platform is most suitable for them to use to publicise their events.Keywords: clinical assessment, online, student perception, medical education, social media

Catastrophic failure of dam structures has often led to severe consequences. The colossal wave receding at a higher velocity from the sudden failure of the dams may obliterate the downstream areas causing loss of lives and property damage. Thus, proper mitigation measures and contingency plans must be formulated beforehand to minimize the impact of such disasters. Consequently, there has been a strong tendency to study dam breach flood modeling using different approaches for both hypothetical dam breach scenarios and real incidents. The technology used for dam breach studies is advancing and a comprehensive review of the existing methodologies would help the modelers in their model development. This paper reviews the state-of-the-art methodologies utilized in studies to propagate the dam break flood wave. Furthermore this guides the selection of methods best suited considering the project-specific requirements and the complexity of project to simulate the risk to the vulnerable areas generated from the dam break flood flow. Different terrain datasets, mesh generation techniques and calibration techniques have been adapted and adhered to improve computational accuracy, stability and efficiency in modeling dam break floods. The use of high-resolution global and site-specific datasets, subgrid models, the choice of roughness coefficients and highresolution time steps have to be investigated thoroughly in these models. The paper reviews the existing methodologies with the strengths and limitations facilitating the future dam breach modelers to select the suitable approach in dam break flood wave modeling. This article is categorized under: Engineering Water > Sustainable Engineering of Water Science of Water > Water Extremes Water and Life > Conservation, Management, and Awareness [ABSTRACT FROM AUTHOR]

Plant-derived terpenoids are extensively used in perfume, food, cosmetic and pharmaceutical industries, and several attempts are being made to produce terpenes in heterologous hosts. Native hosts have evolved to accumulate large quantities of terpenes in specialized cells. However, heterologous cells lack the capacity needed to produce and store high amounts of non-native terpenes, leading to reduced growth and loss of volatile terpenes by evaporation. Here, we describe how to direct the sesquiterpene patchoulol production into cytoplasmic lipid droplets (LDs) in Physcomitrium patens (syn. Physcomitrella patens), by attaching patchoulol synthase (PTS) to proteins linked to plant LD biogenesis. Three different LD-proteins: Oleosin (PpOLE1), Lipid Droplet Associated Protein (AtLDAP1) and Seipin (PpSeipin325) were tested as anchors. Ectopic expression of PTS increased the number and size of LDs, implying an unknown mechanism between heterologous terpene production and LD biogenesis. The expression of PTS physically linked to Seipin increased the LD size and the retention of patchoulol in the cell. Overall, the expression of PTS was lower in the anchored mutants than in the control, but when normalized to the expression the production of patchoulol was higher in the seipin-linked mutants.

EduMe, a web application aimed at enhancing the e-learning experience for students. EduMe comprises four core components: an Automated Personalized Timetable Generator, a Student Behavior Tracking Unit, a Text Summarizer and an Automatic Question Generator and Answer Assessment. These components address challenges such as personalized time management, study focus tracking, efficient content summarization, and interactive question generation. The application provides students with an adaptive learning environment, empowering them to excel in their academic pursuits through personalized resources and guidance. The system is developed using a blend of cutting-edge technologies including image processing, Natural Language Processing, machine learning algorithms and reinforcement learning. Overall, EduMe serves as a valuable tool to support selfstudy methods for undergraduate students, providing them with the necessary resources and guidance to optimize their learning experiences. [ABSTRACT FROM AUTHOR]

Cyanobacterial lipid droplets (LDs) are packed with hydrophobic energy-dense compounds and have great potential for biotechnological expression and the compartmentalization of high value compounds. Nostoc punctiforme normally accumulates LDs containing neutral lipids, and small amounts of heptadecane, during the stationary phase of growth. In this study, we further enhanced heptadecane production in N. punctiforme by introducing extrachromosomal copies of aar/adc genes, and report the discovery of a putative novel lipase encoded by Npun_F5141, which further enhanced alkane production. Extra copies of all three genes in high light conditions resulted in a 16-fold higher accumulation of heptadecane compared to the wild type strain in the exponential phase. LD accumulation during exponential phase also increased massively to accommodate the heptadecane production. A large number of small, less fluorescent LDs were observed at the cell periphery in exponential growth phase, whereas fewer number of highly fluorescent, much larger LDs were localized towards the center of the cell in the stationary phase. These advances demonstrate that cyanobacterial LDs are an ideal model platform to make industrially relevant compounds, such as alkanes, during exponential growth, and provide insight into LD formation in cyanobacteria.

Malaria is a real and constant danger to nearly half of the world’s population of 7.4 billion people. In 2015, 212 million cases were reported along with 429,000 estimated deaths. The World Health Organization recommends artemisinin-based combinatorial therapies, and the artemisinin for this purpose is mainly isolated from the plant Artemisia annua. However, the plant supply of artemisinin is irregular, leading to fluctuation in prices. Here, we report the development of a simple, sustainable, and scalable production platform of artemisinin. The five genes involved in artemisinin biosynthesis were engineered into the moss Physcomitrella patens via direct in vivo assembly of multiple DNA fragments. In vivo biosynthesis of artemisinin was obtained without further modifications. A high initial production of 0.21 mg/g dry weight artemisinin was observed after only 3 days of cultivation. Our study shows that P. patens can be a sustainable and efficient production platform of artemisinin that without further modifications allow for industrial-scale production. A stable supply of artemisinin will lower the price of artemisinin-based treatments, hence become more affordable to the lower income communities most affected by malaria; an important step toward containment of this deadly disease threatening millions every year.

Metabolic engineering is an integrated bioengineering approach, which has made considerable progress in producing terpenoids in plants and fermentable hosts. Here, the full biosynthetic pathway of artemisinin, originating from Artemisia annua, was integrated into the moss Physcomitrella patens. Different combinations of the five artemisinin biosynthesis genes were ectopically expressed in P. patens to study biosynthesis pathway activity, but also to ensure survival of successful transformants. Transformation of the first pathway gene, ADS, into P. patens resulted in the accumulation of the expected metabolite, amorpha-4,11-diene, and also accumulation of a second product, arteannuin B. This demonstrates the presence of endogenous promiscuous enzyme activity, possibly cytochrome P450s, in P. patens. Introduction of three pathway genes, ADS-CYP71AV1-ADH1 or ADS-DBR2-ALDH1 both led to the accumulation of artemisinin, hinting at the presence of one or more endogenous enzymes in P. patens that can complement the partial pathways to full pathway activity. Transgenic P. patens lines containing the different gene combinations produce artemisinin in varying amounts. The pathway gene expression in the transgenic moss lines correlates well with the chemical profile of pathway products. Moreover, expression of the pathway genes resulted in lipid body formation in all transgenic moss lines, suggesting that these may have a function in sequestration of heterologous metabolites. This work thus provides novel insights into the metabolic response of P. patens and its complementation potential for A. annua artemisinin pathway genes. Identification of the related endogenous P. patens genes could contribute to a further successful metabolic engineering of artemisinin biosynthesis, as well as bioengineering of other high-value terpenoids in P. patens.

Plant-derived terpenoids are extensively used in perfume, food, cosmetic and pharmaceutical industries, and several attempts are being made to produce terpenes in heterologous hosts. Native hosts have evolved to accumulate large quantities of terpenes in specialized cells. However, heterologous cells lack the capacity needed to produce and store high amounts of non-native terpenes, leading to reduced growth and loss of volatile terpenes by evaporation. Here, we describe how to direct the sesquiterpene patchoulol production into cytoplasmic lipid droplets (LDs) in Physcomitrium patens (syn. Physcomitrella patens), by attaching patchoulol synthase (PTS) to proteins linked to plant LD biogenesis. Three different LD-proteins: Oleosin (PpOLE1), Lipid Droplet Associated Protein (AtLDAP1) and Seipin (PpSeipin325) were tested as anchors. Ectopic expression of PTS increased the number and size of LDs, implying an unknown mechanism between heterologous terpene production and LD biogenesis. The expression of PTS physically linked to Seipin increased the LD size and the retention of patchoulol in the cell. Overall, the expression of PTS was lower in the anchored mutants than in the control, but when normalized to the expression the production of patchoulol was higher in the seipin-linked mutants. [ABSTRACT FROM AUTHOR]

Securing a molecular toolbox including diverse promoters is essential for genome engineering. However, native promoters have limitations such as the available number or the length of the promoter. In this work, three short synthetic promoters were characterized by using the yellow fluorescent protein Venus. All of the tested promoters were active and showed higher mRNA expression than housekeeping gene PpAct7 , and similar protein expression level to the AtUBQ10 promoter. This study shows that few cis -regulatory elements are enough to establish a strong promoter for continuous expression of genes in plants. Along with this, the study enhance the number of available promotors to be used in P. patens. It also demonstrates the potential to construct multiple non-native promoters on demand, which would aid to resolve one bottleneck in multiple pathway expression in P. patens and other plants. [ABSTRACT FROM AUTHOR]

Bryophytes (including mosses, liverworts and hornworts) are a heterogeneous group of terrestrial plants, which comprise over 24,000 species worldwide. Given the various biological activities reported from bryophytes, they have a huge commercial potential. Due to their minute size and rather small biomass in various ecosystems, bryophytes are a seldom part of ethnomedicine and rarely subject to medicinal and chemical analyses. Still, hundreds of novel natural products have been isolated from bryophytes. Bryophytes have been shown to contain numerous potentially useful natural products, including polysaccharides, lipids, rare amino acids, terpenoids, phenylpropanoids, quinones and many other specialized metabolites. Additionally, different bryophyte extracts and isolated compounds have shown antimicrobial, antiviral, cytotoxic, nematocidal, insecticidal, effects on smooth and non-striated muscles, weight loss, plant growth regulators and allelopathic activities. Bryophytes also cause allergies and contact dermatitis. All these effects highlight bryophytes as potential source for herbal remedies and production of chemicals to be used in various products. [ABSTRACT FROM AUTHOR]

Cyanobacterial lipid droplets (LDs) are packed with hydrophobic energy-dense compounds and have great potential for biotechnological expression and the compartmentalization of high value compounds. Nostoc punctiforme normally accumulates LDs containing neutral lipids, and small amounts of heptadecane, during the stationary phase of growth. In this study, we further enhanced heptadecane production in N. punctiforme by introducing extrachromosomal copies of aar/adc genes, and report the discovery of a putative novel lipase encoded by Npun_F5141, which further enhanced alkane production. Extra copies of all three genes in high light conditions resulted in a 16-fold higher accumulation of heptadecane compared to the wild type strain in the exponential phase. LD accumulation during exponential phase also increased massively to accommodate the heptadecane production. A large number of small, less fluorescent LDs were observed at the cell periphery in exponential growth phase, whereas fewer number of highly fluorescent, much larger LDs were localized towards the center of the cell in the stationary phase. These advances demonstrate that cyanobacterial LDs are an ideal model platform to make industrially relevant compounds, such as alkanes, during exponential growth, and provide insight into LD formation in cyanobacteria. [ABSTRACT FROM AUTHOR]

Simple Summary: Most breast cancers express the estrogen, progesterone, and/or HER2 receptors and patients are treated with inhibitors targeting these receptors. Triple negative breast cancers (TNBCs) lack these receptors and thus patients with TNBC do not benefit from existing targeted therapies. There is a continued search for effective targets for the treatment of these heterogeneous tumors. We identified a class of plant-derived natural products, including yuanhuacine, that selectively kill cells that represent a molecularly defined subtype of TNBC. These compounds also promote expression of an immunological profile that is beneficial for engaging the immune system, which could provide an added benefit in TNBC. The mechanism of action of both the TNBC selectivity and immunological phenotypes is associated with activation of protein kinase C. Yuanhuacine has potent antitumor efficacy in a mouse model of TNBC, identifying a new therapeutic target for the treatment of this deadly disease. The heterogeneity of triple negative breast cancer (TNBC) has led to efforts to further subtype this disease with the hope of identifying new molecular liabilities and drug targets. Furthermore, the finding that TNBC is the most inherently immunogenic type of breast cancer provides the potential for effective treatment with immune checkpoint inhibitors and immune adjuvants. Thus, we devised a dual screen to identify compounds from natural product extracts with TNBC subtype selectivity that also promote the expression of cytokines associated with antitumor immunity. These efforts led to the identification of yuanhuacine (1) as a potent and highly selective inhibitor of the basal-like 2 (BL2) subtype of TNBC that also promoted an antitumor associated cytokine signature in immune cells. The mechanism of action of yuanhuacine for both phenotypes depends on activation of protein kinase C (PKC), defining a novel target for the treatment of this clinical TNBC subtype. Yuanhuacine showed potent antitumor efficacy in animals bearing BL2 tumors further demonstrating that PKC could function as a potential pharmacological target for the treatment of the BL2 subtype of TNBC. [ABSTRACT FROM AUTHOR]

Metabolic engineering is an integrated bioengineering approach, which has made considerable progress in producing terpenoids in plants and fermentable hosts. Here, the full biosynthetic pathway of artemisinin, originating from Artemisia annua, was integrated into the moss Physcomitrella patens. Different combinations of the five artemisinin biosynthesis genes were ectopically expressed in P. patens to study biosynthesis pathway activity, but also to ensure survival of successful transformants. Transformation of the first pathway gene, ADS, into P. patens resulted in the accumulation of the expected metabolite, amorpha-4,11-diene, and also accumulation of a second product, arteannuin B. This demonstrates the presence of endogenous promiscuous enzyme activity, possibly cytochrome P450s, in P. patens. Introduction of three pathway genes, ADS-CYP71AV1-ADH1 or ADS-DBR2-ALDH1 both led to the accumulation of artemisinin, hinting at the presence of one or more endogenous enzymes in P. patens that can complement the partial pathways to full pathway activity. Transgenic P. patens lines containing the different gene combinations produce artemisinin in varying amounts. The pathway gene expression in the transgenic moss lines correlates well with the chemical profile of pathway products. Moreover, expression of the pathway genes resulted in lipid body formation in all transgenic moss lines, suggesting that these may have a function in sequestration of heterologous metabolites. This work thus provides novel insights into the metabolic response of P. patens and its complementation potential for A. annua artemisinin pathway genes. Identification of the related endogenous P. patens genes could contribute to a further successful metabolic engineering of artemisinin biosynthesis, as well as bioengineering of other high-value terpenoids in P. patens. [ABSTRACT FROM AUTHOR]