Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination.

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.

Longitudinal Analysis of the Human B Cell Response to Ebola Virus Infection.

Ebola virus (EBOV) remains a public health threat. We performed a longitudinal study of B cell responses to EBOV in four survivors of the 2014 West African outbreak. Infection induced lasting EBOV-specific immunoglobulin G (IgG) antibodies, but their subclass composition changed over time, with IgG1 persisting, IgG3 rapidly declining, and IgG4 appearing late. Striking changes occurred in the immunoglobulin repertoire, with massive recruitment of naive B cells that subsequently underwent hypermutation. We characterized a large panel of EBOV glycoprotein-specific monoclonal antibodies (mAbs). Only a small subset of mAbs that bound glycoprotein by ELISA recognized cell-surface glycoprotein. However, this subset contained all neutralizing mAbs. Several mAbs protected against EBOV disease in animals, including one mAb that targeted an epitope under evolutionary selection during the 2014 outbreak. Convergent antibody evolution was seen across multiple donors, particularly among VH3-13 neutralizing antibodies specific for the GP1 core. Our study provides a benchmark for assessing EBOV vaccine-induced immunity.

The impact of the Covid-19 pandemic on mental health in Danish school children in 5th to 7th grade.

AIM: We wanted to examine the impact of the Covid-19 pandemic on mental health in Danish school children in 5th to 7th grade (11 to 15 years), and whether the impact differed across age and sex. METHODS: We included 793 and 391 school children from winter 2020 and winter 2021, respectively. Mental health was measured using the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS), Strengths and Difficulties Questionnaire (SDQ), and Brief Resilience Scale (BRS). Data were analyzed by sex using linear regression models adjusting for grade (age), cohabitation, geographical region, employment status of parents, and schools as clusters. RESULTS: Girls in 5th grade and boys in 6th grade during Covid-19 had statistically significant lower well-being (SWEMWBS) compared with before Covid-19. Girls in 5th and 6th grade during Covid-19 had non-statistically significant lower scores on all subscales of SDQ compared with girls before Covid-19. Girls in 7th grade during Covid-19 had statistically significant lower total difficulty score (SDQ) and fewer conduct problems (SDQ) compared with girls before Covid-19. Boys in 5th grade during Covid-19 had statistically significant fewer conduct problems (SDQ) compared with boys before Covid-19. CONCLUSIONS: This study indicates that the Covid-19 pandemic impacted Danish school children differently across sex and grade (age). During Covid-19, mental health tended to be better among the oldest girls and worse among the youngest girls compared with girls before Covid-19. Boys in 6th grade had poorer mental well-being, and boys in 5th grade had fewer conduct problems during Covid-19 compared with before Covid-19.

Maternal and Infant Immune Repertoire Sequencing Analysis Identifies Distinct Ig and TCR Development in Term and Preterm Infants.

Preterm labor (PTL) is the leading cause of neonatal morbidity and mortality worldwide. Whereas many studies have investigated the maternal immune responses that cause PTL, fetal immune cell activation has recently been raised as an important contributor to the pathogenesis of PTL. In this study, we analyzed lymphocyte receptor repertoires in maternal and cord blood from 14 term and 10 preterm deliveries, hypothesizing that the high prevalence of infection in patients with PTL may result in specific changes in the T cell and B cell repertoires. We analyzed TCR ß-chain (TCR-ß) and IgH diversity, CDR3 lengths, clonal sharing, and preferential usage of variable and joining gene segments. Both TCR-ß and IgH repertoires had shorter CDR3s compared with those in maternal blood. In cord blood samples, we found that CDR3 lengths correlated with gestational age, with shorter CDR3s in preterm neonates suggesting a less developed repertoire. Preterm cord blood displayed preferential usage of a number of genes. In preterm pregnancies, we observed significantly higher prevalence of convergent clones between mother/baby pairs than in term pregnancies. Together, our results suggest the repertoire of preterm infants displays a combination of immature features and convergence with maternal TCR-ß clones compared with that of term infants. The higher clonal convergence in PTL could represent mother and fetus both responding to a shared stimulus like an infection. These data provide a detailed analysis of the maternal-fetal immune repertoire in term and preterm patients and contribute to a better understanding of neonate immune repertoire development and potential changes associated with PTL.

Human adaptive immune receptor repertoire analysis-Past, present, and future.

The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane-bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in human biology because they are generated by combinatorial rearrangement of the genomic DNA. The diversity of receptors so generated in populations of lymphocytes enables the human immune system to recognize antigens expressed by pathogens, but also underlies the pathological specificity of autoimmune diseases and the mistargeted immunity in allergies. Several recent technological developments, foremost among them the invention of high-throughput DNA sequencing instruments, have enabled much deeper and thorough evaluation of clones of human B cells and T cells and the antigen receptors they express during physiological and pathogenic immune responses. The evolutionary struggles between host adaptive immune responses and populations of pathogens are now open to greater scrutiny, elucidation of the underlying reasons for successful or failed immunity, and potential predictive modeling, than ever before. Here we give an overview of the foundations, recent progress, and future prospects in this dynamic area of research.

Recent diversification of a marine genus (Tursiops spp.) tracks habitat preference and environmental change.

Understanding the evolution of diversity and the resulting systematics in marine systems is confounded by the lack of clear boundaries in oceanic habitats, especially for highly mobile species like marine mammals. Dolphin populations and sibling species often show differentiation between coastal and offshore habitats, similar to the pelagic/littoral or benthic differentiation seen for some species of fish. Here we test the hypothesis that lineages within the polytypic genus Tursiops track past changes in the environment reflecting ecological drivers of evolution facilitated by habitat release. We used a known recent time point for calibration (the opening of the Bosphorus) and whole mitochondrial genome (mitogenome) sequences for high phylogenetic resolution. The pattern of lineage formation suggested an origin in Australasia and several early divisions involving forms currently inhabiting coastal habitats. Radiation in pelagic environments was relatively recent, and was likely followed by a return to coastal habitat in some regions. The timing of some nodes defining different ecotypes within the genus clustered near the two most recent interglacial transitions. A signal for an increase in diversification was also seen for dates after the last glacial maximum. Together these data suggest the tracking of habitat preference during geographic expansions, followed by transition points reflecting habitat shifts, which were likely associated with periods of environmental change.

Self-care advice for patients after surgery for oesophageal cancer - a mixed-methods systematic review.

PURPOSE: The aim of the literature review was to identify and synthesise research on self-care advice for oesophageal cancer survivors. METHODS: A mixed-methods systematic review and synthesis of existing literature on the topic. Five databases were searched for studies providing information on self-care advice for survivorship after oesophageal cancer surgery, in English, with no time filter. The Critical Appraisal Skills Program was used to assess the risk of bias. Data were presented by textual descriptions and grouping of data. RESULTS: Among the 13 studies included in the review, five pieces of self-care advice were identified; reconstructing eating habits, bed-head elevation, health-promoting advice, monitoring symptoms and body functions, and involving family and friends. The self-care advice was experienced to be hard work, but worth the effort. They also provided reassurance and an increased understanding of bodily changes and social consequences of the disease and treatment. CONCLUSIONS: There are is little evidence-based self-care advice for oesophageal cancer survivors. However, the existing self-care advice was appreciated and contributed to an increased understanding of the situation. Comprehensible and easy-to-follow recommendations should be provided to all oesophageal cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Evidence-based self-care advice helpful for the individual oesophageal cancer survivor may be imperative to cope with the consequences of oesophagectomy after hospital discharge.

Examination of Nursing Staffs' Perceptions of the COVID-19 Vaccine Using the Health Belief Model.

BACKGROUND: The coronavirus (COVID-19) pandemic profoundly impacted patient care across the United States. OBJECTIVE: To examine nursing staffs' perceptions of the COVID-19 vaccine using the Health Belief Model (HBM) as a theoretical framework. METHODS: A cross-sectional, anonymous, web-based survey was completed by practicing nursing staffs throughout the United States. Analyses involved descriptive and comparative statistics. RESULTS: Of the 294 nursing staff who completed surveys, 50% were between 18 and 37 years of age, and 73.1% were registered nurses, with 49.3% employed in a hospital setting. Nursing staff reported their primary reason for vaccination was concern for others (mean: 84.44; SD: 28.26), vaccine prevents spread (mean: 81.85; SD: 28.94), and own health (mean: 79.63; SD: 30.0). Influencing factors that predicted vaccination included age, Wilks' Λ = 0.76, F(32, 919.86) = 2.20, p < .001, η2partial = 0.066, and the vaccine mandate, Wilks' Λ = 0.63, F(8, 249) = 18.61, p < .001, η2partial = 0.374. CONCLUSION: Nursing staffs' perceptions using the HBM as a theoretical framework provided insight into their decisions to receive the COVID-19 vaccine. Further research is warranted to examine nurses' attitudes and factors that influence their decision-making regarding vaccination.

Complete mitochondrial genome phylogeographic analysis of killer whales (Orcinus orca) indicates multiple species.

Killer whales (Orcinus orca) currently comprise a single, cosmopolitan species with a diverse diet. However, studies over the last 30 yr have revealed populations of sympatric "ecotypes" with discrete prey preferences, morphology, and behaviors. Although these ecotypes avoid social interactions and are not known to interbreed, genetic studies to date have found extremely low levels of diversity in the mitochondrial control region, and few clear phylogeographic patterns worldwide. This low level of diversity is likely due to low mitochondrial mutation rates that are common to cetaceans. Using killer whales as a case study, we have developed a method to readily sequence, assemble, and analyze complete mitochondrial genomes from large numbers of samples to more accurately assess phylogeography and estimate divergence times. This represents an important tool for wildlife management, not only for killer whales but for many marine taxa. We used high-throughput sequencing to survey whole mitochondrial genome variation of 139 samples from the North Pacific, North Atlantic, and southern oceans. Phylogenetic analysis indicated that each of the known ecotypes represents a strongly supported clade with divergence times ranging from approximately 150,000 to 700,000 yr ago. We recommend that three named ecotypes be elevated to full species, and that the remaining types be recognized as subspecies pending additional data. Establishing appropriate taxonomic designations will greatly aid in understanding the ecological impacts and conservation needs of these important marine predators. We predict that phylogeographic mitogenomics will become an important tool for improved statistical phylogeography and more precise estimates of divergence times.

Home-based physical activity after treatment for esophageal cancer-A randomized controlled trial.

BACKGROUND: The treatment of most esophageal cancer patients includes chemo(radio)therapy and extensive surgery, causing physical decline with loss of muscles. This trial aimed to test the hypothesis that a tailored home-based physical activity (PA) intervention improves muscle strength and mass in patients having undergone curative treatment for esophageal cancer. METHODS: Patients operated for esophageal cancer 1 year earlier were included in a nationwide randomized controlled trial in Sweden in 2016-2020. The intervention group was randomized to a 12-week home-based exercise program, while the control group was encouraged to maintain routine daily PA. The primary outcomes were changes in maximal/average hand grip strength measured with hand grip dynamometer and lower extremity strength measured using 30-second chair stand test and muscle mass measured using a portable bio-impedance analysis monitor. Intention-to-treat analysis was used, and results were presented as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Among 161 randomized patients, 134 completed the study, 64 in the intervention group and 70 in the control group. Compared with the control group (MD 2.73; 95% CI 1.75-3.71), patients in the intervention group (MD 4.48; 95% CI 3.18-5.80) had statistically significantly (p = 0.03) improved lower extremity strength. No differences were seen for hand grip strength or muscle mass. CONCLUSION: A home-based PA intervention 1 year after surgery for esophageal cancer improves lower extremity muscle strength.

Probable transmission of coxsackie B3 virus from human to chimpanzee, Denmark.

In 2010, a chimpanzee died at Copenhagen Zoo following an outbreak of respiratory disease among chimpanzees in the zoo. Identification of coxsackie B3 virus, a common human pathogen, as the causative agent, and its severe manifestation, raise questions about pathogenicity and transmissibility among humans and other primates.

Psychiatric disorders and mortality among people in homeless shelters in Denmark: a nationwide register-based cohort study.

BACKGROUND: The increased mortality of homeless people compared with non-homeless people might be linked to psychiatric disorders. However, homeless people are, because of their insufficient accommodation, difficult to sample and monitor, which has limited previous studies. We aimed to assess registered psychiatric disorders, mortality, and predictors of mortality in the homeless shelter population in Denmark. METHODS: We did a nationwide, prospective, register-based cohort study of homeless people aged 16 years and older who were registered in the Danish Homeless Register between Jan 1, 1999, and Dec 31, 2009. We calculated the proportion of registered psychiatric disorders, overall and cause-specific standardised mortality ratio (SMR), and life expectancy. Hazard ratios (HRs) were used to assess predictors of death. FINDINGS: 32,711 homeless people (23,040 men and 9671 women) were included in the study population. 14,381 men (62·4%) and 5632 women (58·2%) had registered psychiatric disorders, and 11,286 men (49·0%) and 3564 women (36·9%) had a substance abuse diagnosis. During the study period, 3839 men (16·7%) and 951 women (9·8%) died. The overall SMR for men was 5·6 (95% CI 5·4-5·8) and for women was 6·7 (6·2-7·1), and external causes accounted for 1161 (27·9%) of 4161 deaths for which information on the cause was available. Remaining life expectancy at age 15-24 years was 21·6 years (95% CI 21·2-22·1) and 17·4 years (16·4-18·5) lower for homeless men and women, respectively, than the general population. Registered substance abuse disorder was associated with the highest mortality risk compared with no psychiatric contact registered (adjusted HR 1·4, 95% CI 1·3-1·5 for men; 1·7, 1·4-2·1 for women). INTERPRETATION: Health problems are extensive in the homeless shelter population and there is an urgent need for more sustained efforts to reduce the high morbidity and mortality, especially from external causes. Register data is an important resource to supplement existing knowledge on homeless people with more valid and detailed information. FUNDING: The Danish Council for Independent Research.

[Cognitive late sequelae of COVID-19].

Cognitive sequelae of COVID-19 including memory and concentration difficulties have been observed in 40-65% of persons who have been hospitalised with COVID-19 and 27-50% of non-hospitalised individuals. The cognitive impairments are associated with reduced work function and quality of life. This review recommends systematic cognition screening at long-COVID clinics using brief and feasible objective cognitive screeners, such as the Screen for Cognitive Impairment in Psychiatry (SCIP) and Trail Making Test B or similar tests with sensitivity to cognitive impairment in young populations.

Reinfection with SARS-CoV-2 and Waning Humoral Immunity: A Case Report.

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G. This case of reinfection was one of the first cases of reinfection reported in 2020. With antibody, B cell and T cell analytics, we show correlates of adaptive immunity at reinfection, including a differential response in neutralizing antibodies to a D614G pseudovirus. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

Genetic differentiation among North Atlantic killer whale populations.

Population genetic structure of North Atlantic killer whale samples was resolved from differences in allele frequencies of 17 microsatellite loci, mtDNA control region haplotype frequencies and for a subset of samples, using complete mitogenome sequences. Three significantly differentiated populations were identified. Differentiation based on microsatellite allele frequencies was greater between the two allopatric populations than between the two pairs of partially sympatric populations. Spatial clustering of individuals within each of these populations overlaps with the distribution of particular prey resources: herring, mackerel and tuna, which each population has been seen predating. Phylogenetic analyses using complete mitogenomes suggested two populations could have resulted from single founding events and subsequent matrilineal expansion. The third population, which was sampled at lower latitudes and lower density, consisted of maternal lineages from three highly divergent clades. Pairwise population differentiation was greater for estimates based on mtDNA control region haplotype frequencies than for estimates based on microsatellite allele frequencies, and there were no mitogenome haplotypes shared among populations. This suggests low or no female migration and that gene flow was primarily male mediated when populations spatially and temporally overlap. These results demonstrate that genetic differentiation can arise through resource specialization in the absence of physical barriers to gene flow.

Implementing a New Capstone Leadership Clinical Course.

BACKGROUND: Nurse educators are challenged to ensure clinical education meets the changing health care environments and needs. PROBLEM: New nurses remain unprepared for practice, have insufficient foundational leadership capacities, and lack systems-thinking awareness. APPROACH: Responding to educational gaps, increased enrollment, and scarce clinical placements, faculty used an eclectic education model to develop a new capstone leadership clinical course that included 5 types of experiences. The total acute care clinical hours were reduced, while adding leadership-focused experiences and simulated learning. OUTCOMES: Stakeholders' evaluations indicate the pilot provided opportunities to strengthen students' leadership capacity, systems thinking, and professional identity while still providing sufficient practice managing care of multiple patients, engaging in teamwork, and applying evidence. CONCLUSION: The new clinical course addressed students' transition into practice needs and enrollment capacity issues. Thoughtful planning by invested stakeholders, communication among faculty, and clear expectations are necessary to implement eclectic clinical models.

A qualitative study exploring patient's experiences of oesophageal cancer surgery, through their personal advice to future patients.

PURPOSE: Little is known about how patient's experience-based knowledge and advice after oesophageal cancer surgery may contribute to the understanding of how to improve HRQOL for future patients. In this study the advice that patients who were surgically treated for oesophageal cancer would like to share to future peers, based on their lived experiences were examined. METHOD: A qualitative inductive content analysis was used to analyse one open-ended question from 63 transcribed interviews performed during 2019, within the nationwide Swedish prospective cohort study OSCAR (Oesophageal Surgery on Cancer patients - Adaption and Recovery study). RESULTS: Patients had a broad range of advice to give from their experiences of oesophageal cancer surgery and recovery thereafter. Based on the analysis, three main categories were identified on the advice they wanted to pass on to future peers; health promoting advice, acknowledging the new situation, and advice on embracing support from others. The importance of being physically active, to maintain a positive mind set and to embrace support from both health care professionals as well as family and friends were central experiences that former patients wanted to share with their future peers. CONCLUSION: This study sheds a light on the experiences that patients who have undergone oesophageal cancer surgery have, and what advice they would give to future patients going through the same procedure. The analysis reveals that patients have a variety of advice from their experiences that they want to pass on to future patients. Further studies are needed in order to examine how these advice are received by and can benefit future patients, as well as the pathways of how peer advice is best communicated.

Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues.

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, prepandemic children had class-switched convergent clones to severe acute respiratory syndrome coronavirus 2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. These results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.

mRNA vaccination compared to infection elicits an IgG-predominant response with greater SARS-CoV-2 specificity and similar decrease in variant spike recognition.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected patients exposed to Wuhan-Hu-1 antigens.

Collaborative student-faculty research to support PhD research education.

This paper describes a three-semester hour applied research course taught over three semesters in a revamped PhD research curriculum at a Midwestern high research activity (R2) university-based nursing program. Faculty developed this strategy to help students become adequately prepared nurse scientists. Students and faculty engaged in a collaborative research project to provide students with opportunities to develop, integrate, and apply research knowledge, skills, and attitudes while concurrently advancing through the related research courses. A summary of these experiences and what was learned is organized within a knowledge, skills, and attitudes (KSA) framework. The collaboration between faculty and student peers was essential to students' success in the course. Student and faculty perspectives were used to describe what was learned during the first year this course was taught, together with future recommendations.