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Background: Genome-wide association studies (GWASs) have identified genetic susceptibility variants for both leukocyte telomere length (LTL) and lung cancer susceptibility. Our study aims to explore the shared genetic basis between these traits and investigate their impact on somatic environment of lung tumours. Methods: We performed genetic correlation, Mendelian randomisation (MR), and colocalisation analyses using the largest available GWASs summary statistics of LTL (N=464,716) and lung cancer (N=29,239 cases and 56,450 controls). Principal components analysis based on RNA-sequencing data was used to summarise gene expression profile in lung adenocarcinoma cases from TCGA (N=343). Results: Although there was no genome-wide genetic correlation between LTL and lung cancer risk, longer LTL conferred an increased risk of lung cancer regardless of smoking status in the MR analyses, particularly for lung adenocarcinoma. Of the 144 LTL genetic instruments, 12 colocalised with lung adenocarcinoma risk and revealed novel susceptibility loci, including MPHOSPH6, PRPF6, and POLI. The polygenic risk score for LTL was associated with a specific gene expression profile (PC2) in lung adenocarcinoma tumours. The aspect of PC2 associated with longer LTL was also associated with being female, never smokers, and earlier tumour stages. PC2 was strongly associated with cell proliferation score and genomic features related to genome stability, including copy number changes and telomerase activity. Conclusions: This study identified an association between longer genetically predicted LTL and lung cancer and sheds light on the potential molecular mechanisms related to LTL in lung adenocarcinomas. Funding: Institut National du Cancer (GeniLuc2017-1-TABAC-03-CIRC-1-TABAC17‐022), INTEGRAL/NIH (5U19CA203654-03), CRUK (C18281/A29019), and Agence Nationale pour la Recherche (ANR-10-INBS-09).

Abstract Background Civic engagement, including voting, volunteering, and participating in civic organizations, is associated with better psychological, physical and behavioral health and well-being. In addition, civic engagement is increasingly viewed (e.g., in Robert Wood Johnson Foundation’s Culture of Health action framework) as a potentially important driver for raising awareness of and addressing unhealthy conditions in communities. As such, it is important to understand the factors that may promote civic engagement, with a particular focus on the less-understood, health civic engagement, or civic engagement in health-related and health-specific activities. Using data from a nationally representative sample of adults in the United States (U.S.), we examined whether the extent to which individuals feel they belong in their community (i.e., perceived sense of community) and the value they placed on investing in community health were associated with individuals’ health civic engagement. Methods Using data collected on 7187 nationally representative respondents from the 2018 National Survey of Health Attitudes, we examined associations between sense of community, valued investment in community health, and perceived barriers to taking action to invest in community health, with health civic engagement. We constructed continuous scales for each of these constructs and employed multiple linear regressions adjusting for multiple covariates including U.S. region and city size of residence, educational attainment, family income, race/ethnicity, household size, employment status, and years living in the community. Results Participants who endorsed (i.e., responded with mostly or completely) all 16 sense of community scale items endorsed an average of 22.8% (95%CI: 19.8–25.7%) more of the health civic engagement scale items compared with respondents who did not endorse any of the sense of community items. Those who endorsed (responded that it was an important or top priority) all items capturing valued investment in community health endorsed 14.0% (95%CI: 11.2–16.8%) more of the health civic engagement items than those who did not endorse any valued investment in community health items. Conclusions Health civic engagement, including voting and volunteering to ultimately guide government decisions about health issues, may help improve conditions that influence health and well-being for all. Focusing on individuals’ sense of community and highlighting investments in community health may concurrently be associated with increased health civic engagement and improved community and population health.

Summary: Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting results. Finally, we utilized this method to integrate single-cell transcriptional and protein expression data from SARS-CoV-2-infected patients, revealing antigen-specific B cell subsets after infection. Our results suggest LinQ-View could be helpful for multimodal analysis and purity assessment of CITE-seq datasets that target specific cell populations (e.g., B cells). Motivation: Multimodal single-cell sequencing enables multiple aspects for characterizing the dynamics of cell states and developmental processes. Properly integrating information from multiple modalities is a crucial step for interpreting cell heterogeneity. Here, we present LinQ-View, a computational workflow that provides an effective solution for integrating multiple modalities of CITE-seq data for downstream interpretation. LinQ-View balances information from multiple modalities to achieve accurate clustering results and is specialized in handling CITE-seq data with routine numbers of surface protein features.

Abstract Background After Action Reviews (AARs) provide a means to observe how well preparedness systems perform in real world conditions and can help to identify – and address – gaps in national and global public health emergency preparedness (PHEP) systems. WHO has recently published guidance for voluntary AARs. This analysis builds on this guidance by reviewing evidence on the effectiveness of AARs as tools for system improvement and by summarizing some key lessons about ensuring that AARs result in meaningful learning from experience. Results Empirical evidence from a variety of fields suggests that AARs hold considerable promise as tools of system improvement for PHEP. Our review of the literature and practical experience demonstrates that AARs are most likely to result in meaningful learning if they focus on incidents that are selected for their learning value, involve an appropriately broad range of perspectives, are conducted with appropriate time for reflection, employ systems frameworks and rigorous tools such as facilitated lookbacks and root cause analysis, and strike a balance between attention to incident specifics vs. generalizable capacities and capabilities. Conclusions Employing these practices requires a PHEP system that facilitates the preparation of insightful AARs, and more generally rewards learning. The barriers to AARs fall into two categories: concerns about the cultural sensitivity and context, liability, the political response, and national security; and constraints on staff time and the lack of experience and the requisite analytical skills. Ensuring that AARs fulfill their promise as tools of system improvement will require ongoing investment and a change in mindset. The first step should be to clarify that the goal of AARs is organizational learning, not placing blame or punishing poor performance. Based on experience in other fields, the buy-in of agency and political leadership is critical in this regard. National public health systems also need support in the form of toolkits, guides, and training, as well as research on AAR methods. An AAR registry could support organizational improvement through careful post-event analysis of systems’ own events, facilitate identification and sharing of best practices across jurisdictions, and enable cross-case analyses.

Introduction Out-of-hospital cardiac arrest (OHCA) is a common, life-threatening event encountered routinely by first responders, including police, fire and emergency medical services (EMS). Current literature suggests that there is significant regional variation in outcomes, some of which may be related to modifiable factors. Yet, there is a persistent knowledge gap regarding strategies to guide quality improvement efforts in OHCA care and, by extension, survival. The Enhancing Prehospital Outcomes for Cardiac Arrest (EPOC) study aims to fill these gaps and to improve outcomes.Methods and analysis This mixed-methods study includes three aims. In aim I, we will define variation in OHCA survival to the emergency department (ED) among EMS agencies that participate in the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) in order to sample EMS agencies with high-survival and low-survival outcomes. In aim II, we will conduct site visits to emergency medical systems—including 911/dispatch, police, non-transport fire, and EMS agencies—in approximately eight high-survival and low-survival communities identified in aim I. At each site, key informant interviews and a multidisciplinary focus group will identify themes associated with high OHCA survival. Transcripts will be coded using a structured codebook and analysed through thematic analysis. Results from aims I and II will inform the development of a survey instrument in aim III that will be administered to all EMS agencies in Michigan. This survey will test the generalisability of factors associated with increased OHCA survival in the qualitative work to ultimately build an EPOC Toolkit which will be distributed to a broad range of stakeholders as a practical ‘how-to’ guide to improve outcomes.Ethics and dissemination The EPOC study was deemed exempt by the University of Michigan Institutional Review Board. Findings will be compiled in an ‘EPOC Toolkit’ and disseminated in the USA through partnerships including, but not limited to, policymakers, EMS leadership and health departments.

Background: Community-engaged research engages the community in a collaborative manner to improve the local setting and has been increasingly applied to health services research. These complex studies require collaboration and team building among clinical experts, methodologists, and community stakeholders, yet few examples of this process have been published. Aim: Through a study of community emergency medical services, our aim was to understand team building among content experts and methodologists to advance the framework for adaptive community-engaged research. Methods: We collected process field notes and transcripts from the project kick-off meetings and analyzed the data using an immersion/crystallization process, which is an exploratory qualitative analysis characterized by continual review of the data collected. All 25 members of the study’s research team, who are both local to Michigan and reside out-of-state, were invited to attend. Results: We describe the process of the kick-off event for this community-engaged study and report major themes: collaborating throughout each stage of the kick-off meeting, building trusting relationships by challenging each other’s perspectives and sharing expertise, and gaining shared experiences of learning and understanding of study content and goals. Conclusion: Team-building in community engaged health research requires thoughtful effort, and planned kick-off meeting can be a useful strategy to build a shared vision among content experts and methodologists.

Future technologies based on ferroelectric materials will require new routes to control the nature of polar order. Through a combined experimental and theoretical study of compositionally and strain-graded Ba1-xSrxTiO3 heterostructures, Damodaranet al. demonstrate the ability to engineer large polarization gradients and temperature-stable susceptibilities.

The genus Helichrysum Mill comprises hundreds of species that are mostly flowering perennial shrubs. Some of these plants that belong to the Helichrysum species are used in traditional medicine to treat cough, back pain, diabetes, asthma, digestive problems, menstrual pain, chest pain, kidney disorders, skin disorders, wounds, open sores, among other conditions, but, only a few scientific studies are reported in the literature with sufficient information that validates the acclaimed folkloric benefits of these plants. This review, therefore, provides a comprehensive update of the available information on the cytotoxicity, genotoxicity, anti-proliferative, anti-bacterial, anti-fungal, anti-viral, anti-HIV, anti-malarial, anti-ulcerogenic, anti-tyrosinase, anti-inflammatory, and anti-oxidant activities of selected Helichrysum species of interest: H. petiolare, H. cymocum, H. foetidum, and H. pandurifolium Schrank, using scientific databases as well as electronic and print sources. The ethnobotanical and morphological characteristics as well as the phytochemical composition and biological activities of these plants are elucidated. The scientific rationale for their current use is discussed based on the evidence in the literature. This review highlights the putative use of the Helichrysum species as a reliable source of bioactive compounds for the production of standard commercial drugs to treat many ailments, including those reported in folkloric uses. Further research on the many plants in the genus Helichrysum is recommended to explore their economic importance both as edible crops and medicinal botanicals.

This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI). Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX). This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI). To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm. In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days) or late (42 days) after midthoracic SCI in a rodent model. Early after SCI or TX at 7d, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between spared axonal systems and adaptive plasticity in locomotor networks and highlights a critical window for activity-based rehabilitation. □