Global funding for cancer research between 2016 and 2020: a content analysis of public and philanthropic investments.

BACKGROUND: Cancer is a leading cause of disease burden globally, with more than 19·3 million cases and 10 million deaths recorded in 2020. Research is crucial to understanding the determinants of cancer and the effects of interventions, and to improving outcomes. We aimed to analyse global patterns of public and philanthropic investment in cancer research. METHODS: In this content analysis, we searched the UberResearch Dimensions database and Cancer Research UK data for human cancer research funding awards from public and philanthropic funders between Jan 1, 2016, and Dec 31, 2020. Included award types were project and programme grants, fellowships, pump priming, and pilot projects. Awards focused on operational delivery of cancer care were excluded. Awards were categorised by cancer type, cross-cutting research theme, and research phase. Funding amount was compared with global burden of specific cancers, measured by disability-adjusted life-years, years lived with disability, and mortality using data from the Global Burden of Disease study. FINDINGS: We identified 66 388 awards with total investment of about US$24·5 billion in 2016-20. Investment decreased year-on-year, with the largest drop observed between 2019 and 2020. Pre-clinical research received 73·5% of the funding across the 5 years ($18 billion), phase 1-4 clinical trials received 7·4% ($1·8 billion), public health research received 9·4% ($2·3 billion), and cross-disciplinary research received 5·0% ($1·2 billion). General cancer research received the largest investment ($7·1 billion, 29·2% of the total funding). The most highly funded cancer types were breast cancer ($2·7 billion [11·2%]), haematological cancer ($2·3 billion [9·4%]), and brain cancer ($1·3 billion [5·5%]). Analysis by cross-cutting theme revealed that 41·2% of investment ($9·6 billion) went to cancer biology research, 19·6% ($4·6 billion) to drug treatment research, and 12·1% ($2·8 billion) to immuno-oncology. 1·4% of the total funding ($0·3 billion) was spent on surgery research, 2·8% ($0·7 billion) was spent on radiotherapy research, and 0·5% ($0·1 billion) was spent on global health studies. INTERPRETATION: Cancer research funding must be aligned with the global burden of cancer with more equitable funding for cancer research in low-income and middle-income countries (which account for 80% of cancer burden), both to support research relevant to these settings, and build research capacity within these countries. There is an urgent need to prioritise investment in surgery and radiotherapy research given their primacy in the treatment of many solid tumours. FUNDING: None.

Mesenchymal stem cells induce dynamic immunomodulation of airway and systemic immune cells in vivo but do not improve survival for mice with H1N1 virus-induced acute lung injury.

Introduction: Influenza A virus (IAV)-induced acute lung injury (ALI) is characterized by pronounced proinflammatory activation and respiratory lung dysfunction. In this study, we performed deep immune profiling on airway and circulating immune cells to examine the effect of immunomodulation and therapeutic outcomes of mesenchymal stem cells (MSCs) therapy in mice with IAV-induced ALI. Methods: Animals were inoculated intranasally with H1N1 IAV, followed by intravenous administration of vehicle, or human clinical-grade, bone marrow-derived MSCs 24-h later, and monitored for six days to evaluate the survival. In another set of animals, bronchoalveolar lavage (BAL) fluid and whole blood were collected three days after infection for flow or mass cytometry (CyTOF) immune profiling analysis. Results: Immune cell population and phenotypic shifts in blood were mapped by CyTOF. Increases were observed in granulocytes and myeloid-derived cells in blood from vehicle-treated animals. While MSC treatment accentuated changes in these populations, naïve B, antibody-secreting B cells, and T cells were decreased in MSC-treated animals at day 3. Compared to sham animals, IAV infection induced a significant 5.5-fold increase in BAL total cell counts, including CD4+ and CD8+ T cells, CD19+ B cells, CD11b + Ly6G + neutrophils, and CD11b + Ly6C + monocytes. MSC treatment significantly decreased BAL total cell counts in IAV-infected mice, specifically the number of infiltrating CD4+ T cells and CD11b + Ly6G + neutrophils. In contrast, there were increases in CD8+ T cells, B cells, and monocytes in the alveolar space in MSC-treated animals. Phenotypic immune cell profiling of blood and BAL revealed a significantly higher proportion of the monocyte population with the M2 phenotype (CD206) in MSC-treated animals; however, this failed to confer protective effects in the survival of infected mice or reduce viral titer in the lung. Further investigation revealed that MSCs were susceptible to IAV infection, leading to increased cell death and potentially affecting their efficacy. Conclusion: These findings provided in vivo evidence that MSCs promote the selective recruitment of immune cells to the site of infection during IAV infection, with reductions in proinflammatory phenotypes. However, MSCs offered no survival benefit in IAV-infected animals, possibly due to MSCs' H1N1 IAV susceptibility and subsequent cell death.

Genome Sequences and Characteristics of Six Cluster B1 Mycobacteriophages Discovered at Saint Joseph's University.

We report on six new siphoviruses infecting Mycobacterium smegmatis that were isolated from soil samples collected on the campus of Saint Joseph's University, on the western edge of Philadelphia, Pennsylvania. All phages have circularly permuted genomes that are 68,721 to 68,929 bp long, with an average G+C content of 66.4%.

Experienced based co design: nursing preceptorship educational programme.

BACKGROUND: Patients play a central role in nursing preceptorship relationships, a professional educational relationship between a staff nurse and student nurse that is grounded in providing patient care. Yet the patient experiences and perspectives are largely uncaptured in the literature or represented in current preceptorship education programmes. Furthermore, the lack of student, staff nurse & patient involvement in the design of preceptorship education programmes has been noted. OBJECTIVE: To use a co-design process to develop an innovative educational programme for developing interpersonal and communication skills among nurses who act as preceptors. We sought to (a) clarify experiences and events from all three members involved in a preceptorship relationship (student nurse, preceptor, and patient (SPP) in order to develop a shared understanding of nursing preceptorship relationships and (b) identify the key informational and educational needs recommended by SPP for the educational programme. METHODS: Using the principles and the iterative process of Experienced Based Co Design (EBCD), data was collected from qualitative interviews and used to inform a series of co-design workshops and the co-production of the new educational programme. RESULTS: Twenty-six individuals, including undergraduate student nurses, staff nurses, patients, and a team of nursing, educational and educational technologist experts, contributed to developing a blended learning preceptorship educational programme that consists of three core elements (1) six online reusable learning objects, (2) two role play simulations and (3) a virtual reality storytelling simulated experience. CONCLUSIONS: The EBCD process ensured that the educational programme was developed to meet SPP viewpoints associated with fostering positive interpersonal relationships in a nursing preceptorship. EBCD is a valuable framework for developing human-centred educational resources that combine experiential knowledge (experiences) and scientific knowledge (literature-based knowledge). It facilitated the identification and the development of Interpersonal and Communications skills (IP & C skills) training required within a nursing preceptorship relationship, creating an authentic and memorable learning programme. The structure of EBCD harnesses SPP involvement throughout the research and development process, ensuring transparency and continuity of message, scope, and outcomes.

Nursing preceptorship is a professional educational relationship between a staff nurse and student nurse based on providing patient care. The preceptor is a role model for the student, demonstrating professional roles and practice responsibilities. Furthermore, the preceptor accesses the student's clinical competence, providing valuable feedback, support and guidance. Therefore, an effective preceptor must develop interpersonal, teaching and competency assessment skills. This paper describes a co-design project that involved engaging nursing students, nurses, former patients, and educational and nursing specialists in creating a new nursing preceptorship education programme. The goal was to develop an educational programme that combined scientific evidence with real-life experiences of nursing students, nurses, and patients focusing on developing nurses' interpersonal and communication skills required to be an effective preceptor. Collaborative co-design workshops were held virtually over several months. Activities included one to one interviews, group discussions and feedback on various drafts of the developing educational programme. Participants provided their stories, opinions, and ideas to create an outline of the new programme. The co-design team then collaborated with educational technologists and a virtual reality production company to complete the state-of-the-art innovative educational programme. The programme is now ready to be piloted. It is hoped this new innovative programme that blends both scientific knowledge with real-life experiences will help nurses develop the interpersonal and communication skills required when interacting with students and patients.

Poly(I:C) enhances mesenchymal stem cell control of myeloid cells from COVID-19 patients.

Mesenchymal stem cells (MSCs) are being studied for the treatment of COVID-19-associated critical illness, due to their immunomodulatory properties. Here, we hypothesized that viral mimic-priming improves MSCs' abilities to rebalance the dysregulated immune responses in COVID-19. Transcriptome analysis of poly(I:C)-primed MSCs (pIC-MSCs) showed upregulation of pathways in antiviral and immunomodulatory responses. Together with increased expression of antiviral proteins such as MX1, IFITM3, and OAS1, these changes translated to greater effector functions in regulating monocytes and granulocytes while further enhancing MSCs' ability to block SARS-CoV-2 pseudovirus entry into epithelial cells. Most importantly, the addition of pIC-MSCs to COVID-19 patient whole blood significantly reduced inflammatory neutrophils and increased M2 monocytes while enhancing their phagocytic effector function. We reveal for the first time that MSCs can be primed by Toll-like receptor 3 agonist to improve their ability to rebalance the dysregulated immune responses seen in severe SARS-CoV-2 infection.

Outcomes of ocular evisceration and enucleation in the British Armed Forces from Iraq and Afghanistan.

BACKGROUND/OBJECTIVES: To evaluate outcomes from all British military patients who underwent eye removal during the Iraq and Afghanistan wars. SUBJECTS/METHODS: Retrospective case note review of all patients (n = 19) who had undergone either evisceration or enucleation, on a database of all military patients repatriated to the Royal Centre for Defence Medicine, Birmingham. RESULTS: Twenty eye removals were performed on 19 patients, of which 14 (70%) were eviscerations and 6 (30%) were enucleations. Orbital wall fractures were seen in 12 (61%) patients, with orbital floor fractures being the most common. The eye removal was a primary procedure in five of fourteen eviscerations, and five of six enucleations. Complications were seen after four (28.6%) eviscerations patients and two (33.3%) enucleations. Postoperative pain was problematic after three (21.4%) eviscerations but no enucleations. Orbital implants were placed during three of the five primary enucleations, with good outcomes in two. One patient however required implant retrieval and wound washout due to a high risk of infection and communication with the intra-cranial space. CONCLUSIONS: Evisceration and enucleation are both viable options in the management of severe ocular trauma in military patients. Evisceration and enucleation have similar complication rates and outcomes, and both have low rates of sympathetic ophthalmia. Primary orbital implants can be at high risk in cases with orbital roof fracture, but can provide good outcomes in select patients.

Instrumentation for low noise nanopore-based ionic current recording under laser illumination.

We describe a nanopore-based optofluidic instrument capable of performing low-noise ionic current recordings of individual biomolecules under laser illumination. In such systems, simultaneous optical measurements generally introduce significant parasitic noise in the electrical signal, which can severely reduce the instrument sensitivity, critically hindering the monitoring of single-molecule events in the ionic current traces. Here, we present design rules and describe simple adjustments to the experimental setup to mitigate the different noise sources encountered when integrating optical components to an electrical nanopore system. In particular, we address the contributions to the electrical noise spectra from illuminating the nanopore during ionic current recording and mitigate those effects through control of the illumination source and the use of a PDMS layer on the SiNx membrane. We demonstrate the effectiveness of our noise minimization strategies by showing the detection of DNA translocation events during membrane illumination with a signal-to-noise ratio of ∼10 at 10 kHz bandwidth. The instrumental guidelines for noise minimization that we report are applicable to a wide range of nanopore-based optofluidic systems and offer the possibility of enhancing the quality of synchronous optical and electrical signals obtained during single-molecule nanopore-based analysis.

False positive acetylcholine receptor antibodies in a case of unilateral chronic progressive external ophthalmoplegia: case report and review of literature.

METHODS: We present a rare case with atypical presenting features of unilateral CPEO with a false positive Acetylcholine Receptor Antibody (AchRA) test resulting in diagnostic delay. We illustrate the unilateral nature of this case and demonstrate the caveats of performing myogenic ptosis correction in such patients. We also discuss the differential diagnosis of false positive AchRA, a test commonly performed in the investigation of ptosis. RESULTS: A 34-year old female presented with a more than 3-year history of slowly-progressive, unilateral, right-sided restriction in eye movements and ptosis. Clinical examination showed EOM were grossly restricted in the right eye with a ptosis and normal in the left eye. Serum AchRA was positive on serum enzyme-linked immunosorbent assay (ELISA) however, following two months of oral pyridostigmine therapy there were no signs of clinical improvement. The initial serum sample sent was retested for AchRA by radio-immunoassay (RIA) which came back negative. Subsequently a muscle biopsy was requested which showed the presence of ragged red fibres. CONCLUSION: Unilateral ptosis and ophthalmoplegia is an unusual presentation for CPEO which characteristically produces bilateral symmetrical motility defects. In addition to Myasthenia Gravis elevated AchRA levels have been reported in other autoimmune conditions such as Primary biliary cirrhosis, Eaton Lambert syndrome and Graves's ophthalmopathy. We also highlight the superiority of RIA versus ELISA in the detection of AchRA and illustrate the diagnostic challenge of investigating and managing myogenic ptosis in this complex cohort of patients.

Serratia liquefaciens Causing Severe Ocular Damage in Noncontact Lens Wearer.

Serratia liquefaciens is a rarely encountered gram-negative organism in ophthalmology practice. The only reported ocular infections are from contamination of contact lenses. The authors report the first case of a patient who developed orbital cellulitis secondary to severe S. liquefaciens microbial keratitis.

Isolated diffuse episcleral neurofibroma.

AIMS: To report a rare case of isolated diffuse episcleral neurofibroma and to discuss possible differential diagnoses. CASE REPORT: A 37 year old Caucasian female was found to have an epibulbar tumour arising from the superior aspect of her left eye. Clinical examination revealed a 12 mm × 8 mm "salmon pink" coloured lesion. RESULTS: A biopsy was performed and histopathologic examination and subsequent systemic evaluation showed it to be a rare case of isolated diffuse episcleral neurofibroma. CONCLUSION: There are many differential diagnoses for an epibulbar lesion and neurofibroma should be added to these. Even though a small risk of malignant transformation exists, we recommend a conservative approach for slow growing lesions.

Complications of intracanalicular plugs: a case series.

PURPOSE: Intracanalicular plugs are commonly used in the management of dry eyes. The authors report 3 cases of complications associated with intracanalicular plugs. METHODS: Clinical findings and the management of these patients are presented. RESULTS: The first patient (case 1) is a 47-year-old female with severe dry eyes. Six months after insertion of intracanalicular Form fit hydrogel plugs (OASIS Medical) she developed canaliculitis with Klebsiella oxytoca. The second patient (case 2), a 33-year-old female, who developed left canalicular abscess 5 months following the insertion of bilateral, intracanalicular Form fit hydrogel plugs (OASIS Medical). The third patient (case 3) a 33-year-old female had granulation tissue formation within the left lower canaliculus, 5 years after insertion of intracanalicular plug. The symptoms in the three patients resolved after they underwent canaliculotomy with removal of the plugs. CONCLUSION: Complications of intracanalicular plugs can sometimes outweigh their benefits. These plugs can lodge in the lacrimal outflow system and cause pyogenic granuloma formation and canaliculitis. To our knowledge, until now there have been no reports of complications associated with Form Fit hydrogel plugs (OASIS Medical) and its infective complication with Klebsiella oxytoca.

Simple surgery for severe trichiasis.

PURPOSE: To describe a simple surgical technique for the definitive treatment of severe trichiasis, where the eyelid position is adequate. METHODS: Five anterior lamellar excision procedures are reported, with wounds left to heal by the laissez-faire technique. RESULTS: Postoperatively, all patients were symptom free. No recurrences have been seen with a mean follow-up of 17 months. CONCLUSIONS: Wound healing by secondary intention for periocular defects is not commonly described. Combined anterior lamellar excision and laissez-faire technique shows promising results for trichiasis.