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Abstract Introduction Human papillomavirus (HPV) vaccination protects against HPV-associated cancers and genital warts. Healthy People 2030 goal for HPV vaccine uptake is 80%, but as of 2021, only 58.5% of adolescents are up to date in Georgia. The purpose of the study is to assess the attitudes, vaccine practices, facilitators, and barriers to receiving the HPV vaccine in southwest Georgia. Methods We conducted 40 semi-structured interviews in the United States from May 2020-Feburary 2022 with three different audiences (young adults, parents, and providers and public health professionals) guided by the P3 (patient-, provider-, practice-levels) Model. The audiences were recruited by multiple methods including fliers, a community advisory board, Facebook ads, phone calls or emails to schools and health systems, and snowball sampling. Young adults and parents were interviewed to assess their perceived benefits, barriers, and susceptibility of the HPV vaccine. Providers and public health professionals were interviewed about facilitators and barriers of patients receiving the HPV vaccine in their communities. We used deductive coding approach using a structured codebook, two coders, analyses in MAXQDA, and matrices. Results Out of the 40 interviews: 10 young adults, 20 parents, and 10 providers and public health professionals were interviewed. Emerging facilitator themes to increase the uptake of the HPV vaccine included existing knowledge (patient level) and community outreach, providers’ approach to the HPV vaccine recommendations and use of educational materials in addition to counseling parents or young adults (provider level) and immunization reminders (practice level). Barrier themes were lack of knowledge around HPV and the HPV vaccine (patient level), need for strong provider recommendation and discussing the vaccine with patients (provider level), and limited patient reminders and health education information around HPV vaccination (practice level). Related to socio-ecology, the lack of transportation and culture of limited discussion about vaccination in rural communities and the lack of policies facilitating the uptake of the HPV vaccine (e.g., school mandates) were described as challenges. Conclusion These interviews revealed key themes around education, knowledge, importance of immunization reminders, and approaches to increasing the HPV vaccination in rural Georgia. This data can inform future interventions across all levels (patient, provider, practice, policy, etc.) to increase HPV vaccination rates in rural communities.

Increasing representation of people with disabilities in science and engineering will require systemic changes to the culture around support and accommodations. Equitable interview practices can help foster such changes. We, an interdisciplinary group of disabled and nondisabled early-career scientists who care deeply about making science more accessible to all, present a framework of suggestions based on Universal Design principles for improving the accessibility and equitability of interviews for people with disabilities and other underrepresented groups. We discuss potential challenges that may arise when implementing these suggestions and provide questions to guide discussions about addressing them.

Respiratory health has become a prevailing priority amid the diverse global health challenges that the 21st century brings, due to its substantial impact on individuals and communities on a global scale. Due to rapid advances in medicine, emerging knowledge gaps appear along with new challenges and ethical considerations. While breakthroughs in medical science can bring about encouraging possibilities for better treatments and interventions, they also lead to unanswered questions and areas where further research is warranted. A PubMed search on the topic “global respiratory health priorities” between the years 2000 and 2023 was conducted, which returned 236 articles. Of these, 55 were relevant and selected for inclusion in this article. The selection process took into account literature reviews, opinions from expert groups and careful analysis of existing gaps and challenges within the field; our selection encompasses specific infectious and noninfectious respiratory conditions in both adults and children. The global respiratory health priorities identified were selected on the basis that they have been recognised as critical areas of investigation and potential advancement and they span across clinical, translational, epidemiological and population health domains. Implementing these priorities will require a commitment to fostering collaboration and knowledge-sharing among experts in different fields with the ultimate aim to improve respiratory health outcomes for individuals and communities alike.

Grab bars facilitate bathing and reduce the risk of falls during bathing. Suction cup handholds and rim-mounted tub rails are an alternative to grab bars. The objective of this study was to determine whether older adults could install handholds and tub rails effectively to support bathing transfers. Participants installed rim-mounted tub rails and suction cup handholds in a simulated bathroom environment. Installation location and mechanical loading performance were evaluated. Participant perceptions during device installation and a bathing transfer were characterized. While 85% of suction cup handholds met loading requirements, more than half of participants installed the suction cup handhold in an unexpected location based on existing guidance documents. No rim-mounted tub rails were successfully installed. Participants were confident that the devices had been installed effectively. Suction cup handholds and rim mounted tub rails are easy to install, but clients may need additional guidance regarding where, and how to install them.

Abstract Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against SARS-CoV-2 Omicron XBB sub-variants. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4 + T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023–2024 COVID-19 vaccination campaign.

Abstract Globally, health systems are increasingly striving to deliver evidence based care that improves patients’, caregivers’ and communities’ health outcomes. To deliver this care, more systems are engaging these groups to help inform healthcare service design and delivery. Their lived experiences—experiences accessing and/or supporting someone who accesses healthcare services—are now viewed by many systems as expertise and an important part of understanding and improving care quality. Patients’, caregivers’ and communities’ participation in health systems can range from healthcare organizational design to being members of research teams. Unfortunately, this involvement greatly varies and these groups are often sidelined to the start of research projects, with little to no role in later project stages. Additionally, some systems may forgo direct engagement, focusing solely on patient data collection and analysis. Given the benefits of active patient, caregiver and community participation in health systems on patient health outcomes, systems have begun identifying different approaches to studying and applying findings of patient, caregiver and community informed care initiatives in a rapid and consistent fashion. The learning health system (LHS) is one approach that can foster deeper and continuous engagement of these groups in health systems change. This approach embeds research into health systems, continuously learning from data and translating findings into healthcare practices in real time. Here, ongoing patient, caregiver and community involvement is considered vital for a well functioning LHS. Despite their importance, great variability exists as to what their involvement means in practice. This commentary examines the current state of patient, caregiver and community participation in the LHS. In particular, gaps in and need for resources to support their knowledge of the LHS are discussed. We conclude by recommending several factors health systems must consider in order to increase participation in their LHS. Systems must: (1) assess patients’, caregivers and community understanding of how their feedback are used in the LHS and how collected data are used to inform patient care; (2) review the level and extent of these groups’ participation in health system improvement activities; and (3) examine whether health systems have the workforce, capacity and infrastructure to nurture continuous and impactful engagement.

Introduction All newborns undergo a Complete Examination and Screening of the Neonate (CESoN) to verify the general health and well-being of the neonate and to screen for signs and symptoms of illness and significant congenital disorders, typically within 72 hours of birth. For healthy, term gestation neonates, this examination is usually performed by a qualified healthcare practitioner that is, a midwife, nurse or physician just prior to discharge from the maternity services. As a precursor to modifying and adapting an instrument that measures the quality of performance of the CESoN by healthcare professionals, this review aims to identify, evaluate, synthesise and map the evidence and theory underpinning current practice and the procedural elements of the CESoN.Methods and analysis This review will be guided by the Joanna Briggs Institute methodology for scoping reviews and also the recommendations of the Campbell Collaboration for systematic evidence mapping. Based on the research question, the Person, Concept, Context framework will be used to develop eligibility criteria for inclusion in the review. Eligible information shall be sourced by searching electronic databases including PubMed, Cumulative Index of Nursing and Allied Health Literature, and Scopus, and the published guidance from expert bodies on newborn examination and screening (eg, National Institute for Health and Care Excellence, American Academy of Pediatrics, Royal College of Paediatrics and Child Health) and the grey literature. This study will include primary and secondary research papers, evidence-based guidelines, and expert text and opinions published in English from 2013 to September 2023.Ethics and dissemination Ethical approval is not required for this scoping review and systematic evidence mapping. The results from this study will be disseminated through peer-reviewed format, that is, conference proceedings and peer-reviewed healthcare journals.

Alcohol is present in a large proportion of sexual assault cases. However, research largely overlooks the role that providing alcoholic beverages – particularly those with high-alcohol- content and/or whose flavors mask the taste of alcohol – may have in making young people more vulnerable to being assaulted. This research is especially important given the rise in the availability of sugar-sweetened alcopops and their high-alcohol-content counterparts “supersized alcopops,” which contain up to 5.5 standard alcoholic drinks. In the current study, we examined whether alcopops and supersized alcopops, relative to beer, were involved in disproportionately more sexual assault cases involving victims who were minors (< 18 years old) rather than adults. In this secondary data analysis, we used Nexis Uni to search legal documents for the brands of supersized alcopop (Four Loko), alcopop (Smirnoff Ice), and beer (Bud Light) most commonly consumed by underage drinkers. Inclusion criteria were U.S. sexual assault cases occurring from 2010 to 2019 and involving victims who consumed one of these three alcohol brands. Two researchers coded information from the case facts, compared coding, and reaching consensus. Thirty-six cases were included for analyses. Compared to victims of sexual assault who consumed beer, victims who consumed supersized alcopops or alcopops were significantly more likely to be minors. Similar results were observed after adjusting for the victim being given the alcohol by the perpetrator, which was strongly associated with the victim being a minor. This study provides initial evidence that sexual assault perpetrators may disproportionately use alcopops and supersized alcopops for the sexual victimization of minors.

Background: There is a need for scalable evidence-based psychological interventions for young adolescents experiencing high levels of psychological distress in humanitarian settings and low- and middle-income countries. Poor mental health during adolescence presents a serious public health concern as it is a known predictor of persistent mental disorders in adulthood. This study evaluates the effectiveness of a new group-based intervention developed by the World Health Organization (Early Adolescent Skills for Emotions; EASE), implemented by non-specialists, to reduce young adolescents' psychological distress among mostly Syrian refugees in Lebanon. Methods: We conducted a two-arm, single-blind, individually randomized group treatment trial. Adolescents aged 10 to 14 years who screened positive for psychological distress using the Pediatric Symptom Checklist (PSC) were randomly allocated to EASE or enhanced treatment as usual (ETAU) (1:1.6). ETAU consisted of a single scripted psycho-education home-visit session with the adolescent and their caregivers. EASE consists of seven group sessions with adolescents and three sessions with caregivers. The primary outcome was adolescent-reported psychological distress as measured with the PSC (internalizing, externalizing, and attentional symptoms). Secondary outcomes included depression, posttraumatic stress, well-being, functioning, and caregivers' parenting and distress. All outcomes were assessed at baseline, endline, and 3 months (primary time point) and 12 months follow-up. Results: Due to the COVID-19 pandemic and other adversities in Lebanon at the time of this research, the study was prematurely terminated, resulting in an under-powered trial sample (n = 198 enrolled compared to n = 445 targeted). We screened 604 children for eligibility. The 198 enrolled adolescents were assigned to EASE (n = 80) and ETAU (n = 118), with retention rates between 76.1 and 88.4% across all timepoints. Intent-to-treat analyses demonstrated no between-group differences on any of the outcome measures between the EASE and ETAU. We did observe a significant improvement on the primary outcome equally in the EASE and ETAU groups (−0.90, 95% CI: −3.6, 1.8; p = .52), − a trend that was sustained at three months follow-up. Sub-group analyses, for those with higher depression symptoms at baseline, showed ETAU outperformed EASE on reducing depression symptoms (difference in mean change = 2.7, 95% CI: 0.1, 5.3; p = .04; d = 0.59) and internalizing problems (difference in mean change 1.0, 95% CI: 0.08, 1.9; p = .03; d = 0.56) . Conclusion: No conclusions can be drawn about the comparative effectiveness of the intervention given that the sample was underpowered as a result of early termination. Both EASE and single session psycho-education home visits resulted in meaningful improvements in reducing psychological distress. We did not identify any indications in the data suggesting that EASE was more effective than a single session family intervention in the context of the COVID-19 pandemic and other crises in Lebanon. Fully powered research is needed to evaluate the effectiveness of EASE.

Imbalanced data, a common challenge encountered in statistical analyses of clinical trial datasets and disease modeling, refers to the scenario where one class significantly outnumbers the other in a binary classification problem. This imbalance can lead to biased model performance, favoring the majority class, and affecting the understanding of the relative importance of predictive variables. Despite its prevalence, the existing literature lacks comprehensive studies that elucidate methodologies to handle imbalanced data effectively. In this study, we discuss the binary logistic model and its limitations when dealing with imbalanced data, as model performance tends to be biased towards the majority class. We propose a novel approach to addressing imbalanced data and apply it to publicly available data from the VITAL trial, a large-scale clinical trial that examines the effects of vitamin D and Omega-3 fatty acid to investigate the relationship between vitamin D and cancer incidence in sub-populations based on race/ethnicity and demographic factors such as body mass index (BMI), age, and sex. Our results demonstrate a significant improvement in model performance after our undersampling method is applied to the data set with respect to cancer incidence prediction. Both epidemiological and laboratory studies have suggested that vitamin D may lower the occurrence and death rate of cancer, but inconsistent and conflicting findings have been reported due to the difficulty of conducting large-scale clinical trials. We also utilize logistic regression within each ethnic sub-population to determine the impact of demographic factors on cancer incidence, with a particular focus on the role of vitamin D. This study provides a framework for using classification models to understand relative variable importance when dealing with imbalanced data.

Current SARS-CoV-2 variants evade immune responses induced by approved vaccines. In this study, the authors find that a recombinant prefusion-stabilized Beta spike protein vaccine confers broad neutralization capacity in mice and non-human primates as well as protective antibody and immune memory responses.

We conducted environmental surveillance to detect avian influenza viruses circulating at live poultry markets (LPMs) and poultry farms in Guangxi Autonomous Region, China, where near the China-Vietnam border. From November through April 2017–2018 and 2018–2019, we collected environmental samples from 14 LPMs, 4 poultry farms, and 5 households with backyard poultry in two counties of Guangxi and tested for avian influenza A, H5, H7, and H9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). In addition, we conducted four cross-sectional questionnaire surveys among stall owners on biosecurity practices in LPMs of two study sites. Among 16,713 environmental specimens collected and tested, the median weekly positive rate for avian influenza A was 53.6% (range = 33.5% − 66.0%), including 25.2% for H9, 4.9% for H5, and 21.2% for other avian influenza viruses A subtypes, whereas a total of two H7 positive samples were detected. Among the 189 LPM stalls investigated, most stall owners (73.0%) sold chickens and ducks. Therefore, continued surveillance of the avian influenza virus is necessary for detecting and responding to emerging trends in avian influenza virus epidemiology.

Abstract Misinformation has been a pressing issue since the beginning of the COVID-19 pandemic, threatening our ability to effectively act on the crisis. Nevertheless, little is known about the actual effects of fake news on behavioural intentions. Does exposure to or belief in misinformation about COVID-19 vaccines affect people’s intentions to receive such a vaccine? This paper attempts to address this question via three preregistered experiments (N = 3463). In Study 1, participants (n = 1269) were exposed to fabricated pro- or anti-vaccine information or to neutral true information, and then asked about their intentions to get vaccinated. In Study 2, participants (n = 646) were exposed to true pro- and anti-vaccine information, while Study 3 (n = 1548) experimentally manipulated beliefs in novel misinformation about COVID-19 vaccines by increasing exposure to the information. The results of these three studies showed that exposure to false information about the vaccines had little effect on participants’ intentions to get vaccinated, even when multiple exposures led them to believe the headlines to be more accurate. An exploratory meta-analysis of studies 1 and 3, with a combined sample size of 2683, showed that exposure to false information both supporting and opposing COVID-19 vaccines actually increased vaccination intentions, though the effect size was very small. We conclude by cautioning researchers against equating exposure to misinformation or perceived accuracy of false news with actual behaviours.

BackgroundAvian influenza (AI) virus detections occurred frequently in 2022 and continue to pose a health, economic, and food security risk. The most recent global analysis of official reports of animal outbreaks and human infections with all reportable AI viruses was published almost a decade ago. Increased or renewed reports of AI viruses, especially high pathogenicity H5N8 and H5N1 in birds and H5N1, H5N8, and H5N6 in humans globally, have established the need for a comprehensive review of current global AI virus surveillance data to assess the pandemic risk of AI viruses. ObjectiveThis study aims to provide an analysis of global AI animal outbreak and human case surveillance information from the last decade by describing the circulating virus subtypes, regions and temporal trends in reporting, and country characteristics associated with AI virus outbreak reporting in animals; surveillance and reporting gaps for animals and humans are identified. MethodsWe analyzed AI virus infection reports among animals and humans submitted to animal and public health authorities from January 2013 to June 2022 and compared them with reports from January 2005 to December 2012. A multivariable regression analysis was used to evaluate associations between variables of interest and reported AI virus animal outbreaks. ResultsFrom 2013 to 2022, 52.2% (95/182) of World Organisation for Animal Health (WOAH) Member Countries identified 34 AI virus subtypes during 21,249 outbreaks. The most frequently reported subtypes were high pathogenicity AI H5N1 (10,079/21,249, 47.43%) and H5N8 (6722/21,249, 31.63%). A total of 10 high pathogenicity AI and 6 low pathogenicity AI virus subtypes were reported to the WOAH for the first time during 2013-2022. AI outbreaks in animals occurred in 26 more Member Countries than reported in the previous 8 years. Decreasing World Bank income classification was significantly associated with decreases in reported AI outbreaks (P

Abstract Introduction Over the past decade, numerous efforts have encouraged the realization of the learning health system (LHS) in the United States. Despite these efforts, and promising aims of the LHS, the full potential and value of research conducted within LHSs have yet to be realized. New technology coupled with a catalyzing global pandemic have spurred momentum. In addition, the LHS has lacked a consistent framework within which “best evidence” can be identified. Positive deviance analysis, itself reinvigorated by recent advances in health information technology (IT) and ubiquitous adoption of electronic health records (EHRs), may finally provide a framework through which LHSs can be operationalized and optimized. Methods We describe the synergy between positive deviance and the LHS and how they may be integrated to achieve a continuous cycle of health system improvement. Results As we describe below, the positive deviance approach focuses on learning from high‐performing teams and organizations. Conclusion Such learning can be enabled by EHRs and health IT, providing a lens into how digital clinical interventions are successfully developed and deployed.

Abstract The vision of the learning health system (LHS), conceptualized 15 years ago, is for the rapid generation, use, and spread of high‐quality evidence that yields better health experiences, outcomes, efficiencies, and equity in everyday practice settings across communities. However, despite the emergence of many useful LHS frameworks and examples to guide adoption, large gaps remain in the speed and consistency with which evidence is generated and used across the range of settings from the bedside to the policy table. Gaps in progress are not surprising, however, given the tensions that predictably arise when key stakeholders—researchers, health systems, and funders—comingle in these efforts. This commentary examines eight core tensions that naturally arise and offers practical actions that stakeholders can take to address these tensions and speed LHS adoption. The urgency for attenuating these tensions and accelerating health system improvements has never been higher. Timeliness, rigor, and prioritization can be aligned across stakeholders, but only if all partners are intentional about the operational and cultural challenges that exist.

Bronchiectasis is a common progressive respiratory disease with recognisable radiological abnormalities and a clinical syndrome of cough, sputum production and recurrent respiratory infections. Inflammatory cell infiltration into the lung, in particular neutrophils, is central to the pathophysiology of bronchiectasis. Herein we explore the roles and relationships between infection, inflammation and mucociliary clearance dysfunction in the establishment and progression of bronchiectasis. Microbial and host-mediated damage are important processes underpinning bronchiectasis and the relative contribution of proteases, cytokines and inflammatory mediators to the propagation of inflammation is presented. We also discuss the emerging concept of inflammatory endotypes, defined by the presence of neutrophilic and eosinophilic inflammation, and explore the role of inflammation as a treatable trait. Current treatment for bronchiectasis focuses on treatment of underlying causes, enhancing mucociliary clearance, controlling infection and preventing and treating complications. Data on airway clearance approaches via exercise and mucoactive drugs, pharmacotherapy with macrolides to decrease exacerbations and the usefulness of inhaled antibiotics and bronchodilators are discussed, finishing with a look to the future where new therapies targeting host-mediated immune dysfunction hold promise.

In this review, the Basic and Translational Science Assembly of the European Respiratory Society provides an overview of the 2022 International Congress highlights. We discuss the consequences of respiratory events from birth until old age regarding climate change related alterations in air quality due to pollution caused by increased ozone, pollen, wildfires and fuel combustion as well as the increasing presence of microplastic and microfibres. Early life events such as the effect of hyperoxia in the context of bronchopulmonary dysplasia and crucial effects of the intrauterine environment in the context of pre-eclampsia were discussed. The Human Lung Cell Atlas (HLCA) was put forward as a new point of reference for healthy human lungs. The combination of single-cell RNA sequencing and spatial data in the HLCA has enabled the discovery of new cell types/states and niches, and served as a platform that facilitates further investigation of mechanistic perturbations. The role of cell death modalities in regulating the onset and progression of chronic lung diseases and its potential as a therapeutic target was also discussed. Translational studies identified novel therapeutic targets and immunoregulatory mechanisms in asthma. Lastly, it was highlighted that the choice of regenerative therapy depends on disease severity, ranging from transplantation to cell therapies and regenerative pharmacology.

IntroductionUnderstanding how abundance, productivity and distribution of individual species may respond to climate change is a critical first step towards anticipating alterations in marine ecosystem structure and function, as well as developing strategies to adapt to the full range of potential changes.MethodsThis study applies the NOAA (National Oceanic and Atmospheric Administration) Fisheries Climate Vulnerability Assessment method to 64 federally-managed species in the California Current Large Marine Ecosystem to assess their vulnerability to climate change, where vulnerability is a function of a species’ exposure to environmental change and its biological sensitivity to a set of environmental conditions, which includes components of its resiliency and adaptive capacity to respond to these new conditions.ResultsOverall, two-thirds of the species were judged to have Moderate or greater vulnerability to climate change, and only one species was anticipated to have a positive response. Species classified as Highly or Very Highly vulnerable share one or more characteristics including: 1) having complex life histories that utilize a wide range of freshwater and marine habitats; 2) having habitat specialization, particularly for areas that are likely to experience increased hypoxia; 3) having long lifespans and low population growth rates; and/or 4) being of high commercial value combined with impacts from non-climate stressors such as anthropogenic habitat degradation. Species with Low or Moderate vulnerability are either habitat generalists, occupy deep-water habitats or are highly mobile and likely to shift their ranges.DiscussionAs climate-related changes intensify, this work provides key information for both scientists and managers as they address the long-term sustainability of fisheries in the region. This information can inform near-term advice for prioritizing species-level data collection and research on climate impacts, help managers to determine when and where a precautionary approach might be warranted, in harvest or other management decisions, and help identify habitats or life history stages that might be especially effective to protect or restore.

Most family violence research has been conducted in high-income countries, although family violence rates are higher in low- and middle-income countries (LMICs), and outcomes more severe. Given the strong associations of family violence with substance use and mental illness, the aim of this systematic review was to examine interventions that targeted familial violence and at least one other condition of substance use or mental illness to determine effective treatments in LMICs. We conducted a systematic review of interventions that addressed family violence and mental illness or substance use. A committee of three researchers independently screened titles and abstracts and conducted full-text eligibility assessments. Two researchers conducted a risk of bias assessment. Data were extracted using a structured spreadsheet and narratively synthesized. Our search identified 29 articles produced from 19 studies conducted in 13 LMICs. Most (n = 15) studies randomized to study condition. Lack of blinding was the most common threat. The external validity of studies was generally poor. Fourteen studies had a primary intervention target of family violence, mental health, substance use, economic improvement, or HIV. None of the studies showed improvements in all intervention areas. Child maltreatment was less likely to be addressed than intimate partner violence (IPV). Targeted interventions for substance and mental health mostly improved primary outcomes, although they were less effective in reducing IPV. Evidence-based treatments must be rigorously evaluated before innovations in implementation can occur. Interventions overwhelmingly addressed IPV victimization and should consider how to work with couples and include men and children.

In recent years there has been an explosion of research on misinformation, often involving experiments where participants are presented with fake news stories and subsequently debriefed. In order to avoid potential harm to participants or society, it is imperative that we establish whether debriefing procedures remove any lasting influence of misinformation. In the current study, we followed up with 1547 participants one week after they had been exposed to fake news stories about COVID-19 and then provided with a detailed debriefing. False memories and beliefs for previously-seen fake stories declined from the original study, suggesting that the debrief was effective. Moreover, the debriefing resulted in reduced false memories and beliefs for novel fake stories, suggesting a broader impact on participants' willingness to accept misinformation. Small effects of misinformation on planned health behaviours observed in the original study were also eliminated at follow-up. Our findings suggest that when a careful and thorough debriefing procedure is followed, researchers can safely and ethically conduct misinformation research on sensitive topics.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19, utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin (Ang)-converting enzyme 2 (ACE2). Altering ACE2 levels may affect entry of SARS-CoV-2 and recovery from COVID-19. Decreased cell surface density of ACE2 leads to increased local levels of Ang II and may contribute to mortality resulting from acute lung injury and fibrosis during COVID-19. Studies published early during the COVID-19 pandemic reported that people with cystic fibrosis (PwCF) had milder symptoms, compared to people without CF. This finding was attributed to elevated ACE2 levels and/or treatment with the high efficiency CFTR modulators. Subsequent studies did not confirm these findings reporting variable effects of CFTR gene mutations on ACE2 levels. Transforming growth factor (TGF)-β signaling is essential during SARS-CoV-2 infection and dominates the chronic immune response in severe COVID-19, leading to pulmonary fibrosis. TGF-β1 is a gene modifier associated with more severe lung disease in PwCF but its effects on the COVID-19 course in PwCF is unknown. To understand whether TGF-β1 affects ACE2 levels in the airway, we examined miRNAs and their gene targets affecting SARS-CoV-2 pathogenesis in response to TGF-β1. Small RNAseq and micro(mi)RNA profiling identified pathways uniquely affected by TGF-β1, including those associated with SARS-CoV-2 invasion, replication, and the host immune responses. TGF-β1 inhibited ACE2 expression by miR-136-3p and miR-369-5p mediated mechanism in CF and non-CF bronchial epithelial cells. ACE2 levels were higher in two bronchial epithelial cell models expressing the most common CF-causing mutation in CFTR gene F508del, compared to controls without the mutation. After TGF-β1 treatment, ACE2 protein levels were still higher in CF, compared to non-CF cells. TGF-β1 prevented the modulator-mediated rescue of F508del-CFTR function while the modulators did not prevent the TGF-β1 inhibition of ACE2 levels. Finally, TGF-β1 reduced the interaction between ACE2 and the recombinant spike RBD by lowering ACE2 levels and its binding to RBD. Our data demonstrate novel mechanism whereby TGF-β1 inhibition of ACE2 in CF and non-CF bronchial epithelial cells may modulate SARS-CoV-2 pathogenicity and COVID-19 severity. By reducing ACE2 levels, TGF-β1 may decrease entry of SARS-CoV-2 into the host cells while hindering the recovery from COVID-19 due to loss of the anti-inflammatory and regenerative effects of ACE2. The above outcomes may be modulated by other, miRNA-mediated effects exerted by TGF-β1 on the host immune responses, leading to a complex and yet incompletely understood circuitry.

CCR5 is a co-receptor for many transmitted HIV strains. Here, the authors show that biweekly injection of the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of a CCR5-tropic SHIV.

Abstract Exposure to ‘fake news’ can result in false memories, with possible consequences for downstream behaviour. Given the sharp rise in online misinformation during the coronavirus pandemic, it is important to understand the factors that influence the development of false memories. The present study measured susceptibility to false memories following exposure to fabricated news stories about the pandemic in a sample of 3746 participants. We investigated the effect of individual differences in (1) knowledge about COVID-19, (2) engagement with media or discussion about the coronavirus, (3) anxiety about COVID-19 and (4) analytical reasoning. Notably, objectively and subjectively assessed knowledge about COVID-19 were not significantly correlated. Objectively assessed knowledge was associated with fewer false memories but more true memories, suggesting a true discrimination between true and fake news. In contrast, participants who merely believed themselves to be very knowledgeable were more likely to report a memory for true stories, but showed no reduction in false memories. Similarly, individuals who reported high levels of media engagement or anxiety about COVID-19 reported an increase in true (but not false) memories. Finally, higher levels of analytical reasoning were associated with fewer memories for both true and fabricated stories, suggesting a stricter threshold for reporting a memory for any story. These data indicate that false memories can form in response to fake COVID-19 news and that susceptibility to this misinformation is affected by the individual’s knowledge about and interaction with COVID-19 information, as well as their tendency to think critically.

Abstract Background Multiple trauma in mountain environments may be associated with increased morbidity and mortality compared to urban environments. Objective To provide evidence based guidance to assist rescuers in multiple trauma management in mountain environments. Eligibility criteria All articles published on or before September 30th 2019, in all languages, were included. Articles were searched with predefined search terms. Sources of evidence PubMed, Cochrane Database of Systematic Reviews and hand searching of relevant studies from the reference list of included articles. Charting methods Evidence was searched according to clinically relevant topics and PICO questions. Results Two-hundred forty-seven articles met the inclusion criteria. Recommendations were developed and graded according to the evidence-grading system of the American College of Chest Physicians. The manuscript was initially written and discussed by the coauthors. Then it was presented to ICAR MedCom in draft and again in final form for discussion and internal peer review. Finally, in a face-to-face discussion within ICAR MedCom consensus was reached on October 11th 2019, at the ICAR fall meeting in Zakopane, Poland. Conclusions Multiple trauma management in mountain environments can be demanding. Safety of the rescuers and the victim has priority. A crABCDE approach, with haemorrhage control first, is central, followed by basic first aid, splinting, immobilisation, analgesia, and insulation. Time for on-site medical treatment must be balanced against the need for rapid transfer to a trauma centre and should be as short as possible. Reduced on-scene times may be achieved with helicopter rescue. Advanced diagnostics (e.g. ultrasound) may be used and treatment continued during transport.

The CCR5-specific antibody Leronlimab is being investigated as a novel immunotherapy that can suppress HIV replication with minimal side effects. Here we studied the virological and immunological consequences of Leronlimab in chronically CCR5-tropic HIV-1 infected humans (n = 5) on suppressive antiretroviral therapy (ART) and in ART-naïve acutely CCR5-tropic SHIV infected rhesus macaques (n = 4). All five human participants transitioned from daily combination ART to self-administered weekly subcutaneous (SC) injections of 350 mg or 700 mg Leronlimab and to date all participants have sustained virologic suppression for over seven years. In all participants, Leronlimab fully occupied CCR5 receptors on peripheral blood CD4+ T cells and monocytes. In ART-naïve rhesus macaques acutely infected with CCR5-tropic SHIV, weekly SC injections of 50 mg/kg Leronlimab fully suppressed plasma viremia in half of the macaques. CCR5 receptor occupancy by Leronlimab occurred concomitant with rebound of CD4+ CCR5+ T-cells in peripheral blood, and full CCR5 receptor occupancy was found in multiple anatomical compartments. Our results demonstrate that weekly, self-administered Leronlimab was safe, well-tolerated, and efficacious for long-term virologic suppression and should be included in the arsenal of safe, easily administered, longer-acting antiretroviral treatments for people living with HIV-1. Trial Registration: ClinicalTrials.gov Identifiers: NCT02175680 and NCT02355184.

Background We conducted a matched case–control study in China during the 2013/14–2015/16 influenza seasons to estimate influenza vaccine effectiveness (VE) by dose among children aged 6 months to 8 years. Methods Cases were laboratory-confirmed influenza infections identified through the influenza-like illness sentinel surveillance network in Guangzhou. Age- and sex-matched community controls were randomly selected through the expanded immunization program database. We defined priming as receipt of ≥1 dose of influenza vaccine during the immediate prior season. Results In total, 4,185 case–control pairs were analyzed. Among children 6–35 months, VE for current season dose(s) across the three seasons during 2013/14–2015/16 were 59% (95% Confidence Interval: 44–71%), 12% (−11%,30%), 54% (32–69%); among unprimed children 6–35 months, VE for 1 vs 2 current season doses were 45% (8–67%) vs 65% (46–78%), −2% (−53%,32%) vs 19% (−11%,40%), and 37% (−24%,68%) vs 61% (32–78%). Among children aged 3–8 years, VE for current season dose(s) across study seasons were 62% (36–78%), 43% (22–58%), 32% (1–53%). VE for unprimed children receiving 1 dose only in current season was insignificant or lower than among all children. Conclusion Findings support utility of providing second dose (“booster dose”) of seasonal influenza vaccine to unprimed children aged 6–35 months, and the need to study further dose effect of a booster dose among unprimed children aged 3–8 years in China.

Influenza vaccination coverage in pregnant women in China remains low. In this review, we first provide an overview of the evidence for the use of influenza vaccination during pregnancy. Second, we discuss influenza vaccination policy and barriers to increased seasonal influenza vaccination coverage in pregnant women in China. Third, we provide case studies of successes and challenges of programs for increasing seasonal influenza vaccination in pregnant women from other parts of Asia with lessons learned for China. Finally, we assess opportunities and challenges for increasing influenza vaccination coverage among pregnant women in China.

Long non-coding RNAs (lncRNAs) regulate gene expression. Their expression in alpha-1 antitrypsin (AAT) deficiency has not been investigated. Treatment of AAT deficiency involves infusion of plasma-purified AAT and this augmentation therapy has previously been shown to alter microRNA expression in monocytes of AAT-deficient (ZZ) individuals. Here, we assess the effect of AAT augmentation therapy on the lncRNA expression profile in ZZ monocytes. Peripheral blood monocytes were isolated from ZZ individuals pre (Day 0)- and post (Day 2)-AAT augmentation therapy. Arraystar lncRNA microarray profiling was performed; a total of 17,761 lncRNAs were detectable across all samples. The array identified 7509 lncRNAs with differential expression post-augmentation therapy, 3084 were increased and 4425 were decreased (fold change ≥ 2). Expression of many of these lncRNAs were similarly altered in ZZ monocytes treated ex vivo with 27.5 μM AAT for 4 h. These properties may contribute to the manifold effects of AAT augmentation therapy.

Altered microRNA expression patterns in bronchial brushings from people with versus without cystic fibrosis (CF) relate to functional changes and disease pathophysiology. The expression of microRNAs encoded on the X chromosome is also altered in peripheral blood monocytes of p. Phe508del homozygous versus non-CF individuals. Here we investigate whether levels of the top seven X-linked microRNAs (miR-224-5p, miR-452-5p, miR-450b-5p, miR-542-3p, miR-450a-5p, miR-424-5p, and miR-545-5p) that are significantly increased over 1.5 fold in CF versus non-CF monocytes correlate with lung function. CD14+ monocytes were isolated from males and females with (n = 12) and without cystic fibrosis (n = 12) and examined for the expression of X-linked microRNAs by qRT-PCR array. MicroRNA target mRNA levels were quantified using qRT-PCR. Clinical correlations with lung function data were analysed in the CF cohort. Increasing levels of miR-545-5p correlated moderately with FEV1% predicted (r = -0.4553, p > 0.05) and strongly with exacerbation rate (r = 0.5858, p = 0.0483). miR-224-5p levels were significantly higher in the severe (FEV1

Abstract Introduction Despite the proliferation of pragmatic clinical trials (PCTs) conducted in health care delivery settings, we know relatively little about how practicing clinicians perceive their potential roles in such research. Empirical evidence and practical guidance concerning clinician engagement in research is needed to inform the design and successful implementation of PCTs. Methods We conducted a two‐phase qualitative study to better understand how and to what extent practicing clinicians should be involved in PCTs and to develop guidance for researchers on engaging front‐line clinicians in PCTs. In phase one, clinicians who spend the majority of their time providing direct patient care participated in 90‐min focus groups. In phase two, we conducted key informant interviews with PCT research teams and clinicians participating in the ADAPTABLE (Aspirin Dosing: A Patient‐centric Trial Assessing Benefits and Long‐Term Effectiveness) trial. Results Thirty‐four physicians, nurses, and other care providers from four health care delivery organizations participated in focus groups. Focus group participants stressed the importance of engaging clinicians early in the PCT planning process to identify clinically relevant study questions, provide input on study design, and customize study protocols to fit unique clinic workflows. We conducted 18 interviews with principal investigators, project managers, and clinicians involved in the ADAPTABLE trial across six clinical data research networks. Study team members described trying multiple approaches to optimize in‐clinic recruitment and enrollment of eligible patients. Successful strategies involved several key factors related to research team interactions with eligible patients, clinicians, and clinic staff. Conclusions More active involvement by a range of clinical stakeholders in PCT planning may help researchers avoid common barriers to trial implementation. We propose a “medium‐touch” approach to involving clinicians in PCT recruitment and enrollment that focuses clinician effort where it is most critical—to reassure eligible patients that trial participation is a safe alternative for them.

Summary: Recently approved vaccines have shown remarkable efficacy in limiting SARS-CoV-2-associated disease. However, with the variety of vaccines, immunization strategies, and waning antibody titers, defining the correlates of immunity across a spectrum of antibody titers is urgently required. Thus, we profiled the humoral immune response in a cohort of non-human primates immunized with a recombinant SARS-CoV-2 spike glycoprotein (NVX-CoV2373) at two doses, administered as a single- or two-dose regimen. Both antigen dose and boosting significantly altered neutralization titers and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were associated with distinct levels of protection in the upper and lower respiratory tract. Moreover, NVX-CoV2373 elicited antibodies that functionally targeted emerging SARS-CoV-2 variants. Collectively, the data presented here suggest that a single dose may prevent disease via combined Fc/Fab functions but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants.

Interstitial lung diseases (ILD) are a group of heterogeneous progressive pulmonary disorders, characterised by tissue remodelling and/or fibrotic scarring of the lung parenchyma. ILD patients experience lung function decline with progressive symptoms, poor response to treatment, reduced quality of life and high mortality. ILD can be idiopathic or associated with systemic or connective tissue diseases (CTD) but idiopathic pulmonary fibrosis (IPF) is the most common form. While IPF has a male predominance, women are affected more greatly by CTD and therefore associated ILDs. The mechanisms behind biological sex differences in these progressive lung diseases remain unclear. However, differences in environmental exposures, variable expression of X-chromosome related inflammatory genes and sex hormones play a role. Here, we will outline sex-related differences in the incidence, progression and mechanisms of action of these diseases and discuss existing and novel cellular and pre-clinical studies. Furthermore, we will highlight how sex-differences are not adequately considered in pre-clinical disease models, how gender bias exists in clinical diagnosis and how women are underrepresented in clinical trials. Future action on these observations will hopefully shed light on the role of biological sex in disease development, identify potential targets for intervention and increase female participant numbers in clinical trials.

Abstract Background We sought to assess reporting in China’s Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system’s detection of respiratory infections of public health significance. Methods From February 29–May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. Results Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive.

Abstract Background E39, an HLA‐A2‐restricted, immunogenic peptide derived from the folate‐binding protein (FBP), is overexpressed in multiple malignancies. We conducted a phase I/IIa trial of the E39 + GM‐CSF vaccine with booster inoculations of either E39 or E39′ (an attenuated version of E39) to prevent recurrences in disease‐free endometrial and ovarian cancer patients(pts). Here, we present the final 24‐month landmark analysis. Patients and methods HLA‐A2 + patients receiving E39 + GM‐CSF were included in the vaccine group (VG), and HLA‐A2‐ pts (or HLA‐A2 + patients refusing vaccine) were followed as the control group (CG). VG group received 6 monthly inoculations as the primary vaccine series (PVS) and were randomized to receive either E39 or E39′ booster inoculations. Demographic, safety, immunologic, and disease‐free survival (DFS) data were collected and evaluated. Results Fifty‐one patients were enrolled; 29 in the VG and 22 in the CG. Fourteen patients received