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Sashiananthan Ganesananthan,1 Chunhei Li,1 Anastasia Donnir,1 Anthony Anthony,2 Timothy Woo,1 Agata P Zielinska,3 Ankur Khajuria4,5 1Cardiff University School of Medicine, Cardiff, UK; 2University Hospital Wales, NHS Wales, Cardiff, UK; 3Imperial College London NHS Foundation Trust, London, UK; 4Department of Surgery and Cancer, Imperial College London, London, UK; 5Kellogg College, University of Oxford, Oxford, UKCorrespondence: Ankur KhajuriaDepartment of Surgery and Cancer, Imperial College London, London, UKEmail Ankur.Khajuria09@imperial.ac.ukBackground: The COVID-19 pandemic has created a hiatus in in-person clinical assessments due to safety and logistical concerns. We aimed to evaluate student perception and utility of an online Integrated Structured Clinical Examinations (ISCEs) during the pandemic.Methods: Final-year medical students from a single institution were offered an online mock ISCE through a student-to-student (“near-peer”) teaching-programme. A questionnaire-based cross-sectional study was conducted pre- and post-online mock ISCE.Results: Sixty-four students completed the study. Pre- and post-data showed an increase in confidence (p< 0.0001), less worry regarding the online format (p< 0.0001) and less anxiety about excelling in ISCEs (p< 0.001). Students felt that having done the mock, an online format would more positively affect their overall performance (p=0.007).Conclusion: This study demonstrates a positive change in student perception and confidence in online ISCEs. Online ISCEs are thus feasible, though sole reliance on this format may provide an incomplete assessment of student’s overall clinical competency.Keywords: clinical assessment, online, student perception, medical education, near-peer, COVID-19

Recently, nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity. However, the presentation of a tumor peptide-major histocompatibility complex to T lymphocytes is still a challenge that needs to be addressed for eliciting potent antitumor immunity. Type 1 conventional dendritic cell (cDC1) subset is of particular interest due to its pivotal contribution in the cross-presentation of exogenous antigens to CD8+ T cells. Here, the DC-derived nanovaccine (denoted as Si9GM) selectively targets cDC1s with marginal loss of premature antigen release for effective stimulator of interferon genes (STING)-mediated antigen cross-presentation. Bone marrow dendritic cell (BMDC)-derived membranes, conjugated to cDC1-specific antibody (αCLEC9A) and binding to tumor peptide (OVA257-264), are coated onto dendrimer-like polyethylenimine (PEI)-grafted silica nanoparticles. Distinct molecular weight-cargos (αCLEC9A-OVA257-264 conjugates and 2′3′-cGAMP STING agonists) are loaded in hierarchical center-radial pores that enables lysosome escape for potent antigen-cross presentation and activates interferon type I, respectively. Impressively, Si9GM vaccination leads to the upregulation of cytotoxic T cells, a reduction in tumor regulatory T cells (Tregs), M1/M2 macrophage polarization, and immune response that synergizes with αPD-1 immune checkpoint blockade. This nanovaccine fulfills a dual role for both direct T cell activation as an artificial antigen-presenting cell and DC subset maturation, indicating its utility in clinical therapy and precision medicine.

Abstract Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics for localized diseases with non-invasive treatment modalities may capitalize on the benefits of plant proteins while avoiding their inherent risks. Dupilumab, which is effective against a variety of allergic and autoimmune diseases but has systemic responses and injection-related side effects, may be more beneficial if delivered locally using a small biological form. In this study, we engineered a single-chain variable fragment (scFv) of dupilumab, termed Dup-scFv produced by Nicotiana benthamiana, and evaluated its tissue permeability and anti-inflammatory efficacy in air–liquid interface cultured human nasal epithelial cells (HNECs). Despite showing 3.67- and 17-fold lower binding affinity for IL-4Ra in surface plasmon resonance assays and cell binding assays, respectively, Dup-scFv retained most of the affinity of dupilumab, which was originally high, with a dissociation constant (KD) of 4.76 pM. In HNECs cultured at the air–liquid interface, Dup-scFv administered on the air side inhibited the inflammatory marker CCL26 in hard-to-reach basal cells more effectively than dupilumab. In addition, Dup-scFv had an overall permeability of 0.8% across cell layers compared to undetectable levels of dupilumab. These findings suggest that plant-produced Dup-scFv can be delivered non-invasively to cultured HNESc to alleviate inflammatory signaling, providing a practical approach to utilize plant-based proteins for topical therapeutic applications.

Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory and fibrotic response-driven lung disease that is difficult to cure because it manifests excessive profibrotic cytokines (e.g., TGF-β), activated myofibroblasts, and accumulated extracellular matrix (ECM). In an attempt to develop an inhalation formulation with enhanced antifibrotic efficacy, we sought to fabricate unique aerosolizable inhaled microgels (μGel) that contain nintedanib-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs; n-PN) and pirfenidone-liposomes (p-LP). The aero-μGel was ∼12 μm, resisted phagocytosis by alveolar macrophages in vitro and in vivo, and protected inner-entrapped n-PN and p-LP. The n-PN/p-LP@aero-μGel caused enhanced/extended antifibrotic efficacy in a bleomycin-induced pulmonary fibrosis mouse presumably due to prolonged lung residence. Consequently, the results obtained by intratracheal aerosol insufflation of our n-PN/p-LP@aero-μGel twice a week were much better than those by as many as seven doses of single or mixed applications of n-PN or p-LP. The antifibrotic/pharmacokinetic results for the n-PN/p-LP@aero-μGel included reduced fibrosis progression, restored lung physiological functions, deactivated myofibroblasts, inhibited TGF-β progression, and suppressed ECM component production (collagen I and α-SMA) along with prolonged lung retention time. We believe that our n-PN/p-LP@aero-μGel increased the local availability of both nintedanib and pirfenidone due to evasion of alveolar macrophage phagocytosis and prolonged lung retention with reduced systemic distribution. Through this approach, our inhalation formulation subsequently attenuated fibrosis progression and improved lung function. Importantly, these results hold profound implications in the therapeutic potential of our n-PN/p-LP@aero-μGel to serve as a clinically promising platform, providing significant advancements for improved treatment of many respiratory diseases including IFP.

Abstract Issue COVID-19 has resulted in mortality worldwide and exposed vulnerabilities in public health systems. Although countries have since transitioned to the endemic phase, it is nonetheless important to identify inequities within populations to improve public health strategies in light of another health crisis. Purpose This study aims to offer deeper insights into the sex and age differentials in COVID-19 fatality across different states in Malaysia, from the pandemic’s start to the country’s transition to the endemic phase. Methodology Analyses utilized data on the number of COVID-19 cases and deaths in Malaysia from January 2020 until April 2022. Case fatality rate (CFR) was computed for each state based on sex and age groups, for four periods (January–December 2020, January–June 2021, July–December 2021, and January–April 2022). Principal component analysis (PCA) uncovered patterns in the data and produced a multivariate visualization of the COVID-19 fatality within Malaysia. Findings Findings revealed heterogeneity in fatality and identified several vulnerable states, notably in the northern region (Kelantan, Perlis) and on the East Coast (Sabah, Sarawak). A sex disparity was apparent in Kelantan as the CFR among older females was higher than their male counterparts. Sabah exhibited relatively higher CFR among the child population from 2020 to 2021. Implication The findings deepened our understanding of COVID-19 fatality complexity, providing recommendations for Malaysia’s government in preparing for future health crises. Malaysia’s case study offers lessons on the need to address regional disparities and implement targeted strategies to protect vulnerable subgroups.

Crystalline CaMoO4 NPs were synthesized using a solvothermal method in an autoclave. The synthesized CaMoO4 could detect a signal in the main peak of (112) phase in the XRD pattern. It emits an absorption spectrum in the UV region and an emission spectrum wide range of 380–680 nm. Single-doped Tb3+ ions and Eu3+ ions were used as luminescent materially.. To reproduce the various colors, the amount of Tb3+ ions added was fixed, and the amount of Eu3+ ions was increased to synthesize them. When excited by UV light, the synthesized CaMoO4: [Eu3+]/[Tb3+] displayed various colors from green to yellow, orange, and red. Light-emitting powders of various colors were mixed with polydimethylsiloxane (PDMS) to create a flexible composite sheet that could be folded, rolled, and applied to UV-LED to create unique colors. In addition, it was possible to identify fingerprints on a glass substrate. It was proposed that this could be applied to anti-counterfeiting by manufacturing a solution that could be identified only when applied to banknotes and irradiated with a UV lamp.