Phage Immunoprecipitation-Sequencing Reveals CDHR5 Autoantibodies in Select Patients With Interstitial Lung Disease.

OBJECTIVE: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases. Establishing autoimmunity in ILD impacts prognosis and treatment. Patients with ILD are screened for autoimmunity by measuring antinuclear autoantibodies, rheumatoid factors, and other nonspecific tests. However, this approach may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD. METHODS: We use Phage Immunoprecipitation-Sequencing (PhIP-Seq) to conduct an autoantibody discovery screen of patients with ILD and controls. We screened for novel autoantigen candidates using PhIP-Seq. We next developed a radio-labeled binding assay and validated the leading candidate in 398 patients with ILD recruited from two academic medical centers and 138 blood bank individuals that formed our reference cohort. RESULTS: PhIP-Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among the 17 candidates, we validated CDHR5 and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, patients not previously diagnosed with autoimmunity. Using survival and transplant free-survival data available from one of the two centers, patients with CDHR5 autoantibodies showed worse survival compared with other patients with connective tissue disease ILD. CONCLUSION: We used PhIP-Seq to define a novel CDHR5 autoantibody in a subset of select patients with ILD. Our data complement a recent study showing polymorphisms in the CDHR5-IRF7 gene locus strongly associated with titer of anticentromere antibodies in systemic sclerosis, creating a growing body of evidence suggesting a link between CDHR5 and autoimmunity.

BRWD1 establishes epigenetic states for germinal center initiation, maintenance, and function.

Germinal center (GC) B cells segregate into three subsets that compartmentalize the antagonistic molecular programs of selection, proliferation, and somatic hypermutation. In bone marrow, the epigenetic reader BRWD1 orchestrates and insulates the sequential stages of cell proliferation and Igk recombination. We hypothesized BRWD1 might play similar insulative roles in the periphery. In Brwd1 -/- follicular B cells, GC initiation and class switch recombination following immunization were inhibited. In contrast, in Brwd1 -/- GC B cells there was admixing of chromatin accessibility across GC subsets and transcriptional dysregulation including induction of inflammatory pathways. This global molecular GC dysregulation was associated with specific defects in proliferation, affinity maturation, and tolerance. These data suggest that GC subset identity is required for some but not all GC-attributed functions. Furthermore, these data demonstrate a central role for BRWD1 in orchestrating epigenetic transitions at multiple steps along B cell developmental and activation pathways.

BRWD1 orchestrates small pre-B cell chromatin topology by converting static to dynamic cohesin.

Lymphocyte development consists of sequential and mutually exclusive cell states of proliferative selection and antigen receptor gene recombination. Transitions between each state require large, coordinated changes in epigenetic landscapes and transcriptional programs. How this occurs remains unclear. Here we demonstrate that in small pre-B cells, the lineage and stage-specific epigenetic reader bromodomain and WD repeat-containing protein 1 (BRWD1) reorders three-dimensional chromatin topology to affect the transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters, and coordinated this switch with Igk locus contraction. BRWD1 did so by converting chromatin-bound static to dynamic cohesin competent to mediate long-range looping. ATP-depletion revealed cohesin conversion to be the main energetic mechanism dictating dynamic chromatin looping. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be dictated by lineage contextual mechanisms to facilitate specific cell fate transitions.

Motivators and Barriers to COVID-19 Vaccination in Young Adults Living in the USA.

High rates of COVID-19 infection and lower vaccination rates among young adults aged 18 to 26 in the United States prompted this study to examine motivating factors and barriers to COVID-19 vaccination and identify preferences in COVID-19 vaccine education. Three focus group discussions were completed. Transcribed data were analyzed using thematic analysis. Three key themes were identified including (1) motivating factors to vaccination, (2) barriers to vaccination, and (3) COVID-19 vaccination educational intervention design recommendations. Motivating factors included five relevant subthemes: civic duty, fear related to the disease process; fear related to emerging variants and breakthroughs; fear regarding the suffering of others; and freedom. Barriers included four subthemes: lack of trust, misinformation, politics, and pressure. Attempts to further educate young adults about the COVID-19 vaccine should consider strategies that target motivating factors and barriers while also making accurate information accessible through social media.

PhIP-Seq uncovers novel autoantibodies and unique endotypes in interstitial lung disease.

Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases (CTD). Establishing autoimmunity in ILD impacts prognosis and treatment. ILD patients are screened for autoimmunity by assaying for anti-nuclear autoantibodies, rheumatoid factors and other non-specific tests. However, this approach has not been rigorously validated and may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD. Here, we use Phage Immunoprecipitation-Sequencing (PhIP-Seq) to conduct a large, multi-center unbiased autoantibody discovery screen of ILD patients and controls. PhIP-Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among these 17 candidates, we validated Cadherin Related Family Member 5 (CDHR5) as an autoantigen and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, subjects not previously diagnosed with autoimmunity. Lung tissue of CDHR5 autoreactive patients showed transcriptional profiles consistent with activation of NFκB signaling and upregulation of chitotriosidase (CHIT1), a molecular pathway linked to fibrosis. Our study shows PhIP-Seq uncovers novel autoantibodies in ILD patients not revealed by standard clinical tests. Furthermore, CDHR5 autoantibodies may define a novel molecular endotype of ILD characterized by inflammation and fibrosis.

Antigenic responses are hallmarks of fibrotic interstitial lung diseases independent of underlying etiologies.

Interstitial lung diseases (ILD) are heterogeneous conditions that may lead to progressive fibrosis and death of affected individuals. Despite diversity in clinical manifestations, enlargement of lung-associated lymph nodes (LLN) in fibrotic ILD patients predicts worse survival. Herein, we revealed a common adaptive immune landscape in LLNs of all ILD patients, characterized by highly activated germinal centers and antigen-activated T cells including regulatory T cells (Tregs). In support of these findings, we identified serum reactivity to 17 candidate auto-antigens in ILD patients through a proteome-wide screening using phage immunoprecipitation sequencing. Autoantibody responses to actin binding LIM protein 1 (ABLIM1), a protein highly expressed in aberrant basaloid cells of fibrotic lungs, were correlated with LLN frequencies of T follicular helper cells and Tregs in ILD patients. Together, we demonstrate that end-stage ILD patients have converging immune mechanisms, in part driven by antigen-specific immune responses, which may contribute to disease progression.

Unmet Healthcare Needs and Related Factors Among Immigrants: A Cross-Sectional Secondary Analysis of 2019 Korea Community Health Survey Data.

Immigrants in Korea face numerous difficulties in seeking medical services due to language and cultural differences. Providing medical services to them could be beyond the institutional capacity of the host country owing to factors such as, physical and psychological problems, social unrest, language barriers, and problems adapting to unfamiliar environments. According to Andersen's health service use behavioral model, we used a multifaceted approach to explore the factors influencing the unmet healthcare needs of immigrants in Korea from the Korean health system. This cross-sectional secondary analysis study used data from the 2019 Korea Community Health Survey of 3524 immigrants. Their unmet healthcare needs were calculated using a complex, weighted sample design. Group differences in categorical variables were analyzed using the Rao-Scott chi-square test. Logistic regression analysis was used to analyze the association between unmet healthcare needs and ageing factors. Overall, 262 (7.4%) of surveyed immigrants experienced unmet healthcare needs. Factors influencing unmet healthcare needs were being a woman (OR = 1.41, 95% CI = 1.03-1.94), national primary livelihood security receiver (OR = 1.44, 95% CI = 1.29-1.68), stress (OR = 1.34, 95% CI = 1.26-1.45), perceived health status (poor: OR = 2.35, 95% CI = 1.58-3.52), and perceived health status (moderate: OR = 1.62, 95% CI = 1.18-2.20). Policymakers could focus on these predictors when formulating policy strategies to reduce unmet health care needs. In addition, by effectively delivering services that meet the unmet healthcare needs of immigrants, their right to health is protected.

Black Americans Receiving the COVID-19 Vaccine and Effective Strategies to Overcome Barriers: An Integrative Literature Review.

BACKGROUND: Black Americans have a greater likelihood of serious morbidity or mortality from contracting the coronavirus and represent the lowest percentage of vaccinated individuals by race. This integrative literature review aims to identify the major barriers to Black Americans receiving the COVID-19 vaccine and proposed solutions to improve vaccination rates among this population. METHOD: Databases CINAHL and LitCovid from the National Library of Medicine were utilized to find the articles included in this review. RESULTS: A total of seven articles were identified indicating five barriers preventing Black Americans from being vaccinated against COVID-19 that included (1) mistrust of the medical establishment, (2) uncertainty in vaccine safety, (3) limited access to healthcare, (4) inequitable access to resources, and (5) lower health literacy. The studies also indicated five strategies to increase the desire of Black Americans to be vaccinated including (1) utilizing trusted community leaders, (2) acknowledgment of the history of discrimination and trauma, (3) building more representative clinical trial cohorts, (4) continual investment into community-based organizations, and (5) mobile vaccine clinics. CONCLUSION: The medical establishment in the USA has significant work to do to gain the trust of Black Americans. Many of the strategies to increase vaccine uptake among Black Americans have yet to be implemented which limits the conclusions that can be drawn from them. A future study should examine the outcomes of these proposed solutions to see if they do indeed work as intended and increase vaccination rates among this population.

Gut microbiota modulates bleomycin-induced acute lung injury response in mice.

BACKGROUND: Airway instillation of bleomycin (BLM) in mice is a widely used, yet challenging, model for acute lung injury (ALI) with high variability in treatment scheme and animal outcomes among investigators. Whether the gut microbiota plays any role in the outcome of BLM-induced lung injury is currently unknown. METHODS: Intratracheal instillation of BLM into C57BL/6 mice was performed. Fecal microbiomes were analyzed by 16s rRNA amplicon and metagenomic sequencing. Germ-free mice conventionalization and fecal microbiota transfer between SPF mice were performed to determine dominant commensal species that are associated with more severe BLM response. Further, lungs and gut draining lymph nodes of the mice were analyzed by flow cytometry to define immunophenotypes associated with the BLM-sensitive microbiome. RESULTS: Mice from two SPF barrier facilities at the University of Chicago exhibited significantly different mortality and weight loss during BLM-induced lung injury. Conventionalizing germ-free mice with SPF microbiota from two different housing facilities recapitulated the respective donors' response to BLM. Fecal microbiota transfer from the facility where the mice had worse mortality into the mice in the facility with more survival rendered recipient mice more susceptible to BLM-induced weight loss in a dominant negative manner. BLM-sensitive phenotype was associated with the presence of Helicobacter and Desulfovibrio in the gut, decreased Th17-neutrophil axis during steady state, and augmented lung neutrophil accumulation during the acute phase of the injury response. CONCLUSION: The composition of gut microbiota has significant impact on BLM-induced wasting and death suggesting a role of the lung-gut axis in lung injury.

Benefits of sustained physical activity from middle age to early old age on quality of life in early old age.

This study aimed to examine changes in physical activity (PA) over time (2009-2017) in the same participants and to determine an association between changes in PA and health-related quality of life (HRQoL) in early older adults (n = 994) using data from the Korea Health Panel Survey. HRQoL was measured using the EuroQol system, and the amount of PA was grouped into four activity levels: remained inactive, became inactive, became active, and remained active. The association of changes in PA over 8 years with HRQoL was examined using logistic regression analysis while controlling for socioeconomic and behavioral factors. Total PA decreased from 1859.72 ± 1760.01 MET-minutes in 2009 to 1264.80 ± 1251.14 MET-minutes in 2017 (P < 0.001). In 2017, 142 (14.3%) remained inactive, whereas 419 (42.2%) remained active. Participants who remained inactive in early old age were more likely to be in the lowest 10% HRQoL of the sample (odds ratio = 1.95, 95% confidence interval = 1.09-3.48). These findings indicate that health education and promotion must be prioritized for middle-aged adults, who are relatively inactive, so that they increase their current PA and improve their HRQoL to maximize the benefits of PA in old age.

Association of Smoking Media Literacy with Vietnamese and South Korean Adolescents' Susceptibility to Smoking.

Studies on how smoking media literacy (SML) is associated with susceptibility to smoking among adolescents in South Korea and Vietnam are scarce. Thus, we examined the association of SML with susceptibility to smoking among adolescents in these countries to initiate a collaborative global health program. In total, 460 adolescents (Vietnam: 277, South Korea: 183) aged 15-18 completed an online cross-sectional survey. SML was measured using the 15-item SML scale. Susceptibility to smoking was measured by three questions on future smoking and if offered a cigarette by a friend. A multiple logistic regression model explored the association of SML with susceptibility to smoking. The study revealed that higher SML was significantly associated with lower susceptibility to smoking among Vietnamese, but not South Korean adolescents. Further studies to identify pathways between other factors associated with SML and susceptibility to smoking are needed to develop culture-specific intervention strategies for smoking prevention.

Predictors associated with new nursing faculty's intent to leave nursing academia: teaching preparation in doctoral program, institutional supports, and job satisfaction.

OBJECTIVES: The purpose of this study was to examine the relationships among demographics, doctoral teaching preparation, nurse faculty institutional support, faculty job satisfaction, and intent to leave current nursing academic position in PhD- and DNP-prepared faculty. METHODS: Using a survey research design, invitations to a Qualtrics survey were emailed to nursing program directors. Independent samples t-tests and logistic regression models were used to determine the nature of the relationships. RESULTS: In total, 149 participants completed the survey. Degree type, age, and job satisfaction were significant predictors related to intent to leave nursing academia. Doctoral program teaching preparation and institutional support were not statistically associated with intent to leave nursing academia. CONCLUSIONS: Findings suggest older age, PhD-prepared faculty, and job dissatisfaction were significant factors influencing decisions to leave nursing academia among the doctoral prepared new nursing faculty. Efforts to retain or increase the number of nurse faculty must be prioritized.

Stress and Coping: A Literature Review of Everyday Stressors and Strategies to Cope in Pediatric Patients With Cancer.

Although cancer survival rates are improving, pediatric patients with cancer still face numerous stressors. Using an integrative approach, a literature review was conducted to identify stressors and synthesize effective coping strategies among pediatric patients with cancer. The CINAHL® Complete, ProQuest, and PubMed® databases were searched for relevant studies using key terms. Eight studies were included in the final analysis. Three factors contributing to everyday stressors of pediatric patients with cancer and four major coping categories were identified.

The Mediating Role of Spirituality on Depression, Alcohol Use Disorder, and Problem Gambling Among Korean College Students: A Multiple-Mediation Analysis.

ABSTRACT: Excessive alcohol use and gambling problems among Korean college students in Korea have been recognized as significant public health issues. The purpose of this study was to identify the direct, indirect, and total influence of depression on alcohol use disorder and problem gambling to determine relative magnitudes of the specific mediating effects of spirituality. A cross-sectional correlational survey was conducted in South Korea with 239 college students. Study variables included the Center for Epidemiological Studies Depression Scale, a Spirituality Scale for Koreans, the Alcohol Consumption Questions, and the Korean version of the Canadian Problem Gambling Severity Index. Multiple-mediation analyses were performed. The results found that depression has a negative effect on each of the six subgroups of spirituality. In terms of the effects of spirituality on alcohol use disorder and problem gambling, spirituality was found to have a positive effect only on alcohol use disorder. The relationship between depression and those two addictive behaviors was significantly mediated by spirituality. Bootstrapping revealed that transcendence and connectedness were significantly mediating the relationship between depression and alcohol use disorder. For problem gambling, compassion and connectedness were found to be mediators affecting the relationship between depression and problem gambling. The finding suggests that spirituality's subscales affect two specific addiction problems in different ways. College students' excessive drinking and problem gambling can be prevented by developing and applying an intervention program that strengthens the connectedness of spirituality's subscales.

Depression, Depression Literacy, and Sociodemographic Characteristics of Korean Americans: A Preliminary Investigation.

Despite the rapid growth in the number of Korean Americans (KAs) and the alarmingly high prevalence of depression in this population, relatively little is known about the impact of depression literacy on KAs' depression. This study investigated the prevalence of depressive symptoms among a community-based sample of KA adults; the associations among socio-demographic characteristics, depression literacy, and depressive symptoms; and predictors related to depressive symptoms. A sample of 600 KAs completed depression and depression literacy scales, as well as socio-demographic questionnaires. Data analyses were conducted to assess the association between depressive symptoms, depression literacy, and the covariates. Forty-five percent of participants showed elevated depressive symptoms. Marital status, attained educational level, perceived mental health, and depression literacy were significant predictors of depressive symptoms. Given the high prevalence of depressive symptoms in this population, future research should investigate the causal relationships of various predictors of depression and depression literacy, which will facilitate the development of culturally-appropriate interventions and policies concerning mental health for KAs, and early mental health screening for them.

Network Support Using Social Networking Services to Increase Exercise Adherence Among Korean-Chinese Middle-Aged Migrant Women: Mixed Methods Study.

BACKGROUND: Social networking services (SNSs) are recognized to be a promising approach to easily deliver health interventions and to enhance social support for exercise adherence. However, the patterns and aspects of social support through SNSs have not been reported and their influence on other social-cognitive factors remains inconclusive. OBJECTIVE: Our objective is to explore how social support delivered through SNSs impacts interactions among Korean-Chinese (KC) middle-aged women and to identify how this approach influences social-cognitive factors for exercise (eg, sense of community, self-efficacy for exercise, and social support for exercise). METHODS: A mixed methods design was used. Text analysis of SNS messages and text mining using the Korean Natural Language Application (KoALA) were conducted. Social-cognitive factors (eg, sense of community, self-efficacy for exercise, and social support for exercise) were assessed at baseline and after 12 weeks using a structured questionnaire. A comparison of social-cognitive factors at baseline and at 12 weeks was conducted to identify any potential significant changes, using the Wilcoxon signed-rank test. RESULTS: A total of 259 SNS messages were collected from 24 KC women, distributed among four chat groups, who participated in a 12-week walking intervention program between August and October 2018. The individual average frequency of chatting via the SNS was 10.79 (range 0-34) and the most frequent type of social support through the SNS was network support (172/259, 66.4%). The most common words extracted from the SNS were Health, Exercise, Participation, and We. Overall, the perceived levels of sense of community (P<.001) and social support for exercise (P=.002) were significantly increased at 12 weeks compared with baseline. Group 1 (P=.03) and Group 4 (P=.03), whose members demonstrated the highest frequency of network support, experienced a significant increase only in the level of sense of community. CONCLUSIONS: By integrating these data and conducting a mixed methods analysis, we observed that among the types of social support, network support was a key point for the promotion of social-cognitive factors in increasing exercise adherence. Therefore, network support through SNS-based interventions should be considered as a useful strategy to help vulnerable migrant populations make changes to exercise behaviors.

Factors Associated with the Health Literacy on Social Determinants of Health: A Focus on Socioeconomic Position and Work Environment.

Though impressive progress has been made in healthcare worldwide, many people still experience disproportionate health burdens and inequities in healthcare services. For establishing sustainable development goals, health literacy on social determinants of health (HL-SDH) has been recognized as a key to creating better social and physical environments. In particular, low levels of health literacy among industrial workers are considered as a major barrier to benefitting from the progress made in healthcare. This study aimed to describe levels of HL-SDH and to examine the relationships among socioeconomic status, working environment, and HL-SDH among workers in Korea. A total of 660 workers from an online panel participated in Korea from 30 May to 7 June 2018. The Korean version of HL-SDH instrument consisted of 33 items and four dimensions: access, understand, appraise, and apply. Descriptive statistics, a t-test, ANOVA, and multiple regression analysis were conducted. The mean score of HL-SDH was 2.48. Perceived mental health status, annual income, and the number of employees per worksite were found to be statistically significant factors related to HL-SDH (F = 3.64, p = <0.001). The HL-SDH score was considerably higher, indicating that nursing interventions to enhance HL-SDH are required for health promotion, especially among workers in poor social and working environments.

Factors affecting depression in high school students with chronic illness: A nationwide cross-sectional study in South Korea.

Chronic illnesses have been associated with poor mental health and depression. Given the fact that a large number of adolescents are suffering from chronic illnesses in South Korea, it is important to identify factors that contribute to depression in this population so that appropriate interventions can be developed. In order to achieve this aim, a large-scale, nationwide, cross-sectional study was performed. The study used data obtained from the 2016 Korean Children and Youth Panel Survey which included first-year high school students diagnosed with one or more of the following chronic illnesses: asthma, allergic rhinitis, atopic dermatitis, obesity, heart disease, and diabetes. A multiple regression analysis revealed that female, poor school adjustment, social withdrawal, low subjective health status, low self-esteem, and a shorter duration of exercise during physical education classes were significant predictors of depression. Thus, depression in adolescents with chronic illness seems to be closely linked to social, physical, and academic factors. These findings may aid the development of appropriate intervention programs that specifically target these factors for this vulnerable population.

Evaluation of Health Literacy and Depression Literacy Among Korean Americans.

Low health literacy is closely related to a higher rate of hospitalization and of emergency services usage, leading to billions of dollars in avoidable health care costs and contributing to individuals' poor physical and mental health. While Korean Americans (KAs) have a high prevalence of general health and mental health problems, relatively little is known about their health and mental health literacy, specifically their depression literacy. This study aims to evaluate KAs' health literacy and depression literacy, as related to sociodemographic characteristics. An exploratory study was conducted with 681 community-residing adult KAs using the Center for Epidemiologic Studies Depression (CES-D) Scale, the Depression Literacy Questionnaire (D-Lit), and the One-Question Health Literacy Scale. Data analyses were performed using one-way analysis of variance and ordinal logistic regression of health literacy, a multiple linear regression model of depression literacy. Findings indicate a positive correlation between depression literacy and health literacy. Health literacy was also significantly related to religion, English language proficiency, income, education, and perceived physical health. Additionally, depression literacy was significantly related to age, Korean language preference over English, and education. Health literacy and depression literacy education are warranted to address low health literacy and depression literacy among KAs to reduce their health and mental health disparities.

Factors associated with maintenance of smoking cessation in adolescents after implementation of tobacco pricing policy in South Korea: Evidence from the 11th Youth Health Behavior Survey.

As a part of Korea's smoking cessation policy, the price of tobacco was increased in January 2015. Initially, the smoking rate among adolescents began to decrease. The current data, however, show that the adolescent smoking rate is on the rise. Alongside price policies, there is a need to further understand additional preventive measures that promote successful smoking cessation by identifying the factors that influence maintenance of smoking cessation in adolescents. This study aimed to identify the factors that influence smoking cessation in adolescents after attempting smoking cessation after increase in tobacco price. The study used large-scale, nationwide, secondary data obtained from the Korean Youth Risk Behavior Web-Based Survey. The sample included a total of 627 subjects who reported an attempt to quit smoking after the tobacco price increased. Descriptive statistics, t test, the χ2 test, and multiple logistic regression were used. The results showed that household economic status, school type, suicidal ideation, experience of exposure to secondhand smoke at home, and experience of witnessing teaching staff smoking were significant factors related to maintenance of smoking cessation among adolescents. To increase the success rate of smoking cessation, future intervention programs should include school environment structure and address emotional and psychological issues such as suicide.