Cellular milieu in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is globally the most prevalent renal cancer. The cells of origin in ccRCC have been identified as proximal tubular epithelial cells (PTEC); however, the transcriptomic pathways resulting in the transition from normal to malignant PTEC state have remained unclear. Immunotherapy targeting checkpoints have revolutionized the management of ccRCC, but a sustained clinical response is achieved in only a minority of ccRCC patients. This indicates that our understanding of the mechanisms involved in the malignant transition and resistance to immune checkpoint therapy in ccRCC is unclear. This review examines recent single-cell transcriptomics studies of ccRCC to clarify the transition of PTEC in ccRCC development, and the immune cell types, states, and interactions that may limit the response to targeted immune therapy, and finally suggests stromal cells as key drivers in recurrent and locally invasive ccRCC. These and future single-cell transcriptomics studies will continue to clarify the cellular milieu in the ccRCC microenvironment, thus defining actional clinical, therapeutic, and prognostic characteristics of ccRCC

Impact of General Practitioner Education on Acceptance of an Adjuvanted Seasonal Influenza Vaccine among Older Adults in England.

Seasonal vaccination against influenza and in-pandemic COVID-19 vaccination are top public health priorities; vaccines are the primary means of reducing infections and also controlling pressures on health systems. During the 2018-2019 influenza season, we conducted a study of the knowledge, attitudes, and behaviours of 159 general practitioners (GPs) and 189 patients aged ≥65 years in England using a combination of qualitative and quantitative approaches to document beliefs about seasonal influenza and seasonal influenza vaccine. GPs were surveyed before and after a continuing medical education (CME) module on influenza disease and vaccination with an adjuvanted trivalent influenza vaccine (aTIV) designed for patients aged ≥65 years, and patients were surveyed before and after a routine visit with a GP who participated in the CME portion of the study. The CME course was associated with significantly increased GP confidence in their ability to address patients' questions and concerns about influenza disease and vaccination (p < 0.001). Patients reported significantly increased confidence in the effectiveness and safety of aTIV after meeting their GP. Overall, 82.2% of the study population were vaccinated against influenza (including 137 patients vaccinated during the GP visit and 15 patients who had been previously vaccinated), a rate higher than the English national average vaccine uptake of 72.0% that season. These findings support the value of GP-patient interactions to foster vaccine acceptance

Impact of General Practitioner Education on Acceptance of an Adjuvanted Seasonal Influenza Vaccine among Older Adults in England.

Seasonal vaccination against influenza and in-pandemic COVID-19 vaccination are top public health priorities; vaccines are the primary means of reducing infections and also controlling pressures on health systems. During the 2018-2019 influenza season, we conducted a study of the knowledge, attitudes, and behaviours of 159 general practitioners (GPs) and 189 patients aged ≥65 years in England using a combination of qualitative and quantitative approaches to document beliefs about seasonal influenza and seasonal influenza vaccine. GPs were surveyed before and after a continuing medical education (CME) module on influenza disease and vaccination with an adjuvanted trivalent influenza vaccine (aTIV) designed for patients aged ≥65 years, and patients were surveyed before and after a routine visit with a GP who participated in the CME portion of the study. The CME course was associated with significantly increased GP confidence in their ability to address patients' questions and concerns about influenza disease and vaccination (p < 0.001). Patients reported significantly increased confidence in the effectiveness and safety of aTIV after meeting their GP. Overall, 82.2% of the study population were vaccinated against influenza (including 137 patients vaccinated during the GP visit and 15 patients who had been previously vaccinated), a rate higher than the English national average vaccine uptake of 72.0% that season. These findings support the value of GP-patient interactions to foster vaccine acceptance

Development and usability evaluation of a nutrition and lifestyle guidance application for people living with and beyond cancer

There is a need to provide accessible information for health care professionals and for people living beyond treatment. Mobile and digital health technologies provide an ideal platform to access diet and nutrition guidance that is both trusted and evidence-based and so that people know how to alter and monitor eating patterns and behaviours to improve the quality of life. Participatory design and usability evaluation approaches have been utilised to develop a nutrition and lifestyle guidance smartphone application for both people living with and beyond cancer, and for health care professionals involved in advising such patients. The challenges centred on the design, development and evaluation of the first version of a new mobile application named ‘Life Beyond’ are presented. This proof of concept application aims to centralise evidence-based nutrition and lifestyle guidance for those living beyond cancer. It enables users to obtain guidance and information, create and track nutrition and activity related goals and track their progress in the completion of these goals. Consistent feedback from participatory design and usability evaluations drove this research and helped to create an initial solution that met the user expectations. The System Usability Scale (SUS) score of 67.69 denotes an ‘average’ usability and hence further development. More research of extensive end user engagement is needed before an optimal solution is disseminated

Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments

Available transcriptomes of the mammalian kidney provide limited information on the spatial interplay between different functional nephron structures due to the required dissociation of tissue with traditional transcriptome-based methodologies. A deeper understanding of the complexity of functional nephron structures requires a non-dissociative transcriptomics approach, such as spatial transcriptomics sequencing (ST-seq). We hypothesize that the application of ST-seq in normal mammalian kidneys will give transcriptomic insights within and across species of physiology at the functional structure level and cellular communication at the cell level. Here, we applied ST-seq in six mice and four human kidneys that were histologically absent of any overt pathology. We defined the location of specific nephron structures in the captured ST-seq datasets using three lines of evidence: pathologist's annotation, marker gene expression, and integration with public single-cell and/or single-nucleus RNA-sequencing datasets. We compared the mouse and human cortical kidney regions. In the human ST-seq datasets, we further investigated the cellular communication within glomeruli and regions of proximal tubules–peritubular capillaries by screening for co-expression of ligand–receptor gene pairs. Gene expression signatures of distinct nephron structures and microvascular regions were spatially resolved within the mouse and human ST-seq datasets. We identified 7,370 differentially expressed genes (padj < 0.05) distinguishing species, suggesting changes in energy production and metabolism in mouse cortical regions relative to human kidneys. Hundreds of potential ligand–receptor interactions were identified within glomeruli and regions of proximal tubules–peritubular capillaries, including known and novel interactions relevant to kidney physiology. Our application of ST-seq to normal human and murine kidneys confirms current knowledge and localization of transcripts within the kidney. Furthermore, the generated ST-seq datasets provide a valuable resource for the kidney community that can be used to inform future research into this complex organ

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Illness perceptions of COVID-19 in Europe: Predictors, impacts and temporal evolution

Objective: Illness perceptions (IP) are important predictors of emotional and behavioral responses in many diseases. The current study aims to investigate the COVID-19-related IP throughout Europe. The specific goals are to understand the temporal development, identify predictors (within demographics and contact with COVID-19) and examine the impacts of IP on perceived stress and preventive behaviors. Methods: This was a time-series-cross-section study of 7, 032 participants from 16 European countries using multilevel modeling from April to June 2020. IP were measured with the Brief Illness Perception Questionnaire. Temporal patterns were observed considering the date of participation and the date recoded to account the epidemiological evolution of each country. The outcomes considered were perceived stress and COVID-19 preventive behaviors. Results: There were significant trends, over time, for several IP, suggesting a small decrease in negativity in the perception of COVID-19 in the community. Age, gender, and education level related to some, but not all, IP. Considering the self-regulation model, perceptions consistently predicted general stress and were less consistently related to preventive behaviors. Country showed no effect in the predictive model, suggesting that national differences may have little relevance for IP, in this context. Conclusion: The present study provides a comprehensive picture of COVID-19 IP in Europe in an early stage of the pandemic. The results shed light on the process of IP formation with implications for health-related outcomes and their evolution. © Copyright © 2021 Dias Neto, Nunes da Silva, Roberto, Lubenko, Constantinou, Nicolaou, Lamnisos, Papacostas, Höfer, Presti, Squatrito, Vasiliou, McHugh, Monestès, Baban, Alvarez-Galvez, Paez-Blarrina, Montesinos, Valdivia-Salas, Ori, Lappalainen, Kleszcz, Gloster, Karekla and Kassianos

Patterns of psychological responses among the public during the early phase of COVID-19: A cross-regional analysis

This study aimed to compare the mediation of psychological flexibility, prosociality and coping in the impacts of illness perceptions toward COVID-19 on mental health among seven regions. Convenience sampled online survey was conducted between April and June 2020 from 9130 citizens in 21 countries. Illness perceptions toward COVID-19, psychological flexibility, prosociality, coping and mental health, socio-demographics, lockdown-related variables and COVID-19 status were assessed. Results showed that psychological flexibility was the only significant mediator in the relationship between illness perceptions toward COVID-19 and mental health across all regions (all ps = 0.001–0.021). Seeking social support was the significant mediator across subgroups (all ps range = <0.001–0.005) except from the Hong Kong sample (p = 0.06) and the North and South American sample (p = 0.53). No mediation was found for problem-solving (except from the Northern European sample, p = 0.009). Prosociality was the significant mediator in the Hong Kong sample (p =0.016) and the Eastern European sample (p = 0.008). These findings indicate that fostering psychological flexibility may help to mitigate the adverse mental impacts of COVID-19 across regions. Roles of seeking social support, problem-solving and prosociality vary across regions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Mental Health Status of Healthcare Workers During the COVID-19 Outbreak An International Study

Background: The COVID-19 pandemic is a massive health crisis that has exerted enormous physical and psychological pressure. Mental healthcare for healthcare workers (HCWs) should receive serious consideration. This study served to determine the mental-health outcomes of 1,556 HCWs from 45 countries who participated in the COVID-19 IMPACT project, and to examine the predictors of the outcomes during the first pandemic wave. Methods: Outcomes assessed were self-reported perceived stress, depression symptom, and sleep changes. The predictors examined included sociodemographic factors and perceived social support. Results: The results demonstrated that half of the HCWs had moderate levels of perceived stress and symptoms of depression. Half of the HCWs (n = 800, 51.4%) had similar sleeping patterns since the pandemic started, and one in four slept more or slept less. HCWs reported less perceived stress and depression symptoms and higher levels of perceived social support than the general population who participated in the same project. Predictors associated with higher perceived stress and symptoms of depression among HCWs included female sex, not having children, living with parents, lower educational level, and lower social support. Discussion: The need for establishing ways to mitigate mental-health risks and adjusting psychological interventions and support for HCWs seems to be significant as the pandemic continues