Symptom phenotyping in people with cystic fibrosis during acute pulmonary exacerbations using machine-learning K-means clustering analysis.

INTRODUCTION: People with cystic fibrosis (PwCF) experience frequent symptoms associated with chronic lung disease. A complication of CF is a pulmonary exacerbation (PEx), which is often preceded by an increase in symptoms and a decline in lung function. A symptom cluster is when two or more symptoms co-occur and are related; symptom clusters have contributed meaningful knowledge in other diseases. The purpose of this study is to discover symptom clustering patterns in PwCF during a PEx to illuminate symptom phenotypes and assess differences in recovery from PExs. METHODS: This study was a secondary, longitudinal analysis (N = 72). Participants at least 10 years of age and being treated with intravenous antibiotics for a CF PEx were enrolled in the United States. Symptoms were collected on treatment days 1-21 using the CF Respiratory Symptom Diary (CFRSD)-Chronic Respiratory Symptom Score (CRISS). K-means clustering was computed on day 1 symptom data to detect clustering patterns. Linear regression and multi-level growth models were performed. RESULTS: Symptoms significantly clustered based on severity: low symptom (LS)-phenotype (n = 42), high symptom (HS)-phenotype (n = 30). HS-phenotype had worse symptoms and CRISS scores (p< 0.01) than LS-phenotype. HS-phenotype was associated with spending 5 more nights in the hospital annually (p< 0.01) than LS-phenotype. HS-phenotype had worse symptoms over 21 days than LS-phenotype (p< 0.0001). CONCLUSION: Symptoms significantly cluster on day 1 of a CF-PEx. PwCF with HS-phenotype spend more nights in the hospital and are less likely to experience the same resolution in symptoms by the end of PEx treatment than LS-phenotype.

Individual and Contextual Correlates of Latent Bystander Profiles toward Racist Hate Speech: A Multilevel Person-centered Approach.

Prior research into bystander responses to hate speech has utilized variable-centered analyses - such approaches risk simplifying the complex nature of bystander behaviors. Hence, the present study used a person-centered analysis to investigate latent hate speech bystander profiles. In addition, individual and classroom-level correlates associated with the various profiles were studied. The sample included 3225 students in grades 7-9 (51.7% self-identified as female; 37.2% with immigrant background) from 215 classrooms in Germany and Switzerland. The latent profile analysis revealed that four distinct profiles could be distinguished: Passive Bystanders (34.2%), Defenders (47.3%), Revengers (9.8%), and Contributors (8.6%). Multilevel logistic regression models showed common and distinct correlates. For example, students who believed that certain social groups are superior were more likely to be Revengers and Contributors than Passive Bystanders, students who felt more connected with teachers were more likely to be Defenders, and students who were more open to diversity were less likely to be Contributors than Passive Bystanders. Students were less likely Defenders and more likely Revengers and Contributors than Passive Bystanders in classrooms with high rates of hate speech perpetration. Further, in classrooms with high hate speech intervention, students were more likely to be Defenders and less likely to be Contributors than Passive Bystanders. In classrooms with stronger cohesion, students were more likely to be Defenders and less likely to be Contributors than Passive Bystanders. In conclusion, the findings add to our understanding of bystander profiles concerning racist hate speech and the relevance of individual and classroom-level factors in explaining various profiles of bystander behavior.

Longitudinal Associations between Different Types of Sexting, Adolescent Mental Health, and Sexual Risk Behaviors: Moderating Effects of Gender, Ethnicity, Disability Status, and Sexual Minority Status.

The present study investigated the moderating effect of adolescent demographic variables in the longitudinal associations among different types of sexting, mental health (i.e., depression, self-harm, subjective health complaints), and sexual risk behaviors. There were 1113 adolescents (ages 14-17 years; Mage = 16.36; SDage = .81; 50% female) from six high schools located in the United States included in this study. Adolescents completed questionnaires on their sexting behaviors, mental health, and sexual risk behaviors during the ninth grade; in tenth grade, they completed questionnaires on mental health and sexual risk behaviors. Non-consensual sexting and pressured sexting were both related positively to each of the mental health variables and sexual risk behaviors. The relationship between non-consensual sexting and depressive symptoms was stronger for girls, ethnic minorities, those adolescents with disabilities, and sexual minorities. Similar patterns were found for pressured sexting, non-suicidal self-harm, and subjective health complaints. The relationships between pressured sexting and sexual risk behaviors were stronger for girls, ethnic minorities, those adolescents with disabilities, and those who identified as sexual minorities. Research focused on the relationships among different types of sexting, mental health, and sexual risk behaviors is important as such research facilitates the development of evidence-based recommendations for sexting harm prevention and sexual education programs.

Problematic Use of the Internet and Well-Being among Youth from a Global Perspective: A Mediated-Moderated Model of Socio-Emotional Factors.

Problematic Use of the Internet (PUI) is characterized as the inability to control one's internet use or as an excessive use of the internet that may result in social, psychological, and emotional difficulties (Fernandes et al., 2019). It is regarded nowadays as an increasingly worrisome public heath issue, especially among youth. This study explored the contexts in which youth PUI occurs and its associations with socio-emotional functioning that may lead to a decrease in one's sense of well-being. We conducted this exploration among 783 middle school students from the US (425 students; 54.27%) and Israel (358 students; 45.73%). The overall age of both samples ranged between 12 and 16 (M = 13.94, SD = 1.59). In the Israeli sample, 49.1% of the students were girls and 50.9% were boys, whereas in the US sample, 48.8% were girls and 51.2% were boys. The study examined the role of depressive mood, loneliness, resilience, self-control, and school engagement in mediating the relationship between PUI and well-being, and how country of origin might moderate these relationships. Results indicate PUI was related to lower well-being only for the US sample. Yet, for both samples, higher loneliness was related to lower well-being, and higher school engagement was related to higher well-being. A moderated mediation analysis revealed the socio-emotional variables were all mediators in these associations, but differently for each country sample. The study results are discussed according to key factors required for developing intervention programs for coping with youth PUI behaviors.

Molecular and functional correction of a deep intronic splicing mutation in CFTR by CRISPR-Cas9 gene editing.

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The 10th most common mutation, c.3178-2477C>T (3849+10kb C>T), involves a cryptic, intronic splice site. This mutation was corrected in CF primary cells homozygous for this mutation by delivering pairs of guide RNAs (gRNAs) with Cas9 protein in ribonucleoprotein (RNP) complexes that introduce double-strand breaks to flanking sites to excise the 3849+10kb C>T mutation, followed by DNA repair by the non-homologous end-joining pathway, which functions in all cells of the airway epithelium. RNP complexes were delivered to CF basal epithelial cell by a non-viral, receptor-targeted nanocomplex comprising a formulation of targeting peptides and lipids. Canonical CFTR mRNA splicing was, thus, restored leading to the restoration of CFTR protein expression with concomitant restoration of electrophysiological function in airway epithelial air-liquid interface cultures. Off-target editing was not detected by Sanger sequencing of in silico-selected genomic sites with the highest sequence similarities to the gRNAs, although more sensitive unbiased whole genome sequencing methods would be required for possible translational developments. This approach could potentially be used to correct aberrant splicing signals in several other CF mutations and other genetic disorders where deep-intronic mutations are pathogenic.

Predicting return of lung function after a pulmonary exacerbation using the cystic fibrosis respiratory symptom diary-chronic respiratory infection symptom scale.

Background: Pulmonary exacerbations (PExs) in people with cystic fibrosis (PwCF) are associated with increased healthcare costs, decreased quality of life and the risk for permanent decline in lung function. Symptom burden, the continuous physiological and emotional symptoms on an individual related to their disease, may be a useful tool for monitoring PwCF during a PEx, and identifying individuals at high risk for permanent decline in lung function. The purpose of this study was to investigate if the degree of symptom burden severity, measured by the Cystic Fibrosis Respiratory Symptom Diary (CFRSD)- Chronic Respiratory Infection Symptom Scale (CRISS), at the onset of a PEx can predict failure to return to baseline lung function by the end of treatment. Methods: A secondary analysis of a longitudinal, observational study (N = 56) was conducted. Data was collected at four time points: year-prior-to-enrollment annual appointment, termed "baseline", day 1 of PEx diagnosis, termed "Visit 1", day 10-21 of PEx diagnosis, termed "Visit 2" and two-weeks post-hospitalization, termed "Visit 3". A linear regression model was performed to analyze the research question. Results: A regression model predicted that recovery of lung function decreased by 0.2 points for every increase in CRISS points, indicating that participants with a CRISS score greater than 48.3 were at 14% greater risk of not recovering to baseline lung function by Visit 2, than people with lower scores. Conclusion: Monitoring CRISS scores in PwCF is an efficient, reliable, non-invasive way to determine a person's status at the beginning of a PEx. The results presented in this paper support the usefulness of studying symptoms in the context of PEx in PwCF.

A roadmap for social determinants of health and biological nursing research in the National Institute of Nursing Research 2022-2026 Strategic Plan: Optimizing health and advancing health equity using antiracist framing.

BACKGROUND: Health equity is essential for improving the well-being of all individuals and groups, and research remains a critical element for understanding barriers to health equity. While considering how to best support research that acknowledges current health challenges, it is crucial to understand the role of social justice frameworks within health equity research and the contributions of minoritized researchers. Additionally, there should be an increased understanding of the influence of social determinants of health on biological mechanisms. PURPOSE: Biological health equity research seeks to understand and address health disparities among historically excluded populations. DISCUSSION: While there are examples of studies in this area led by minoritized researchers, some individuals and groups remain understudied due to underfunding. Research within minoritized populations must be prioritized to authentically achieve health equity. Furthermore, there should be increased funding from National Institutes of Health to support minoritized researchers working in this area.

ART Praxis: Evidence-Based Strategies for Antiracist Teaching in Nursing.

AIM: This integrative review seeks to provide effective teaching and learning strategies for teaching about racism and advancing health equity. BACKGROUND: Most faculty preparation remains devoid of an exploration of racism and the skills to critique how historical events and socialization create and reinforce the biases that influence how we teach and provide care. It is difficult to teach what we do not know. METHOD: Using Whittmore and Knafl's approach, we conducted an integrative review of multidisciplinary literature from 2009 to 2021 to uncover best practices for teaching about racism. Seven databases yielded 55 relevant articles from 18 disciplines. RESULTS: Four themes emerged illuminating effective strategies for teaching and learning about systemic racism: encounter education, reflection, discussion, and activism. CONCLUSION: Findings of this review align with Mezirow's transformative learning theory and highlight the importance of not just "doing" antiracist activities in a course but "becoming" an antiracist educator.

A sum of its parts: A systematic review evaluating biopsychosocial and behavioral determinants of perinatal depression.

Introduction: Depression is one of the most common yet underdiagnosed perinatal complications and our understanding of the pathophysiology remains limited. Though perinatal depression is considered to have a multifactorial etiology, integrative approaches to investigation are minimal. This review takes an integrative approach to systematically evaluate determinants and potential interactions among determinants of perinatal depression across four domains (i.e., biological, behavioral, environmental, social) and appraise the quality of methods applied. Methods: Four databases (i.e., PubMed, CINAHL, APA PsycInfo, and Web of Science) were systematically searched to identify studies examining determinants of perinatal depression in adult perinatal persons (≥ 18 years). Articles were excluded if the outcomes were not focused on perinatal persons and depression or depression symptoms, the evaluation of depression was specific to a discrete facet of the perinatal period with probable psychological consequences (e.g., abortion, fetal/infant loss, adoption), or was considered grey literature. The Critical Appraisal Skills Programme and AXIS tools were used to guide and standardize quality appraisal assessments and determine the level of risk of bias. Results: Of the 454 articles identified, 25 articles were included for final review. A total of 14 categories of determinants were investigated: biological (5), behavioral (4), social and environmental (5). Though only 28% of studies simultaneously considered determinants under more than one domain, a pattern of interactions with the tryptophan pathway emerged when determinants across domains were aggregated. Concerns for risk of bias were noted or were unclear for three types of bias: 13 (52%) selection bias, 3 (12%) recall bias, and 24 (96%) measurement bias. Conclusions: Future research is needed to explore interactions among determinants and the tryptophan pathway; to strengthen the methods applied to this area of inquiry; and to generate evidence for best practices in reporting, selecting, and applying methods for measuring determinants and perinatal depression.

Cancer-related cognitive impairment in racial and ethnic minority groups: a scoping review.

PURPOSE: Disparities in cognitive function among racial and ethnic groups have been reported in non-cancer conditions, but cancer-related cognitive impairment (CRCI) in racial and ethnic minority groups is poorly understood. We aimed to synthesize and characterize the available literature about CRCI in racial and ethnic minority populations. METHODS: We conducted a scoping review in the PubMed, PsycInfo, and Cumulative Index to Nursing and Allied Health Literature databases. Articles were included if they were published in English or Spanish, reported cognitive functioning in adults diagnosed with cancer, and characterized the race or ethnicity of the participants. Literature reviews, commentaries, letters to the editor, and gray literature were excluded. RESULTS: Seventy-four articles met the inclusion criteria, but only 33.8% differentiated the CRCI findings by racial or ethnic subgroups. There were associations between cognitive outcomes and the participants' race or ethnicity. Additionally, some studies found that Black and non-white individuals with cancer were more likely to experience CRCI than their white counterparts. Biological, sociocultural, and instrumentation factors were associated with CRCI differences between racial and ethnic groups. CONCLUSIONS: Our findings indicate that racial and ethnic minoritized individuals  may be disparately affected by CRCI. Future research should use standardized guidelines for measuring and reporting the self-identified racial and ethnic composition of the sample; differentiate CRCI findings by racial and ethnic subgroups; consider the influence of structural racism in health outcomes; and develop strategies to promote the participation of members of racial and ethnic minority groups.

Adolescent Cyberbullies' Attributions: Longitudinal Linkages to Cyberbullying Perpetration.

The aim of the present study was to examine cyberbullies' attributions pertaining to their perpetration of cyberbullying, and how such attributions relate to their cyberbullying behaviors six months later. Participants were 216 adolescents (M = 13.46, SD = 0.62 years; 55% female) from the suburbs of a large Midwestern city in the United States. They were interviewed face-to-face in the fall of 2018 concerning why they acted in negative ways toward peers online or through text messages. They also answered questionnaires regarding how often they perpetrated face-to-face bullying and cyberbullying during the fall of 2018 and spring of 2019. The attributions of revenge, convenience, anger, and anonymity each predicted cyberbullying at the second time point while controlling for face-to-face bullying perpetration. Results from this study provide important information to the literature regarding cyberbullies' attributions for perpetrating cyberbullying, and how such attributions predict future cyberbullying perpetration. These findings are important for the development of antibullying programs that might aim to change adolescents' attributions for cyberbullying perpetration to reduce continued engagement in these behaviors.

Cyberbullying Involvement and Depression among Elementary School, Middle School, High School, and University Students: The Role of Social Support and Gender.

One aim of this study was to investigate differences in cyberbullying involvement (i.e., victimization, bystanding, perpetration) across four age groups, including 234 elementary school students (4th and 5th grades; 51% female), 363 middle school students (6th through 8th grades; 53% female), 341 high school students (9th through 12th grade; 51% female), and 371 university students (all four years; 60% female). Another aim was to examine the age group differences in the associations between cyberbullying involvement and depression, as well as the moderating effect of social support from parents and friends. Participants completed questionnaires on cyberbullying involvement, depression, and social support from parents and friends. Findings revealed that middle school students were more often involved in cyberbullying as victims, bystanders, and perpetrators, followed by high school and university students, and elementary school students. High school and university students did not differ on their cyberbullying involvement. Gender moderated these relationships for elementary school students, with boys more often involved in cyberbullying perpetration and victimization than girls. In addition, female university students witnessed cyberbullying more so than males. Social support from parents buffered against the negative effects of cyberbullying involvement on depression across all age groups. Results were similar for social support from friends, but only for middle school and high school students. Gender did not influence the associations among age groups, cyberbullying involvement, and depression. The results have implications for designing prevention and intervention programs and ensuring that such programs consider age.

Comparison of commercial DNA extraction kits for whole metagenome sequencing of human oral, vaginal, and rectal microbiome samples.

Introduction: Advancements in DNA extraction and sequencing technologies have been fundamental in deciphering the significance of the microbiome related to human health and pathology. Whole metagenome shotgun sequencing (WMS) is gaining popularity in use compared to its predecessor (i.e., amplicon-based approaches). However, like amplicon-based approaches, WMS is subject to bias from DNA extraction methods that can compromise the integrity of sequencing and subsequent findings. The purpose of this study was to evaluate systematic differences among four commercially available DNA extraction kits frequently used for WMS analysis of the microbiome. Methods: Oral, vaginal, and rectal swabs were collected in replicates of four by a healthcare provider from five participants and randomized to one of four DNA extraction kits. Two extraction blanks and three replicate mock community samples were also extracted using each extraction kit. WMS was completed with NovaSeq 6000 for all samples. Sequencing and microbial communities were analyzed using nonmetric multidimensional scaling and compositional bias analysis. Results: Extraction kits differentially biased the percentage of reads attributed to microbial taxa across samples and body sites. The PowerSoil Pro kit performed best in approximating expected proportions of mock communities. While HostZERO was biased against gram-negative bacteria, the kit outperformed other kits in extracting fungal DNA. In clinical samples, HostZERO yielded a smaller fraction of reads assigned to Homo sapiens across sites and had a higher fraction of reads assigned to bacterial taxa compared to other kits. However, HostZERO appears to bias representation of microbial communities and demonstrated the most dispersion by site, particularly for vaginal and rectal samples. Conclusions: Systematic differences exist among four frequently referenced DNA extraction kits when used for WMS analysis of the human microbiome. Consideration of such differences in study design and data interpretation is imperative to safeguard the integrity of microbiome research and reproducibility of results.

Climate change and the adverse impact on the health and well-being of women and girls from the Women's Health Expert Panel of the American Academy of Nursing.

Climate change has measurable adverse impact on the general and reproductive health of women and girls. Multinational government organizations, private foundations, and consumer groups identify anthropogenic disruptions in social and ecological environments as the primary threats to human health this century. Drought, micronutrient shortage, famine, mass migration, conflict over resources, and effects on mental health resulting from displacement and war are challenging effects to manage. The most severe effects will be felt by those with the least resources to prepare for and adapt to changes. Climate change is a phenomenon of interest to women's health professionals because women and girls are more vulnerable to the effects due to a combination of physiologic, biologic, cultural, and socioeconomic risk factors. Nurses, with our scientific foundation, human-centered approach, and position of trust in societies can be leaders in efforts at mitigation, adaptation, and building resilience in response to changes in our planetary health.

Effects of the Prevention Program "HateLess. Together against Hatred" on Adolescents' Empathy, Self-efficacy, and Countering Hate Speech.

Currently, there is a lack of empirically evaluated prevention programs targeting hate speech among adolescents. This is problematic because hate speech jeopardizes adolescents' well-being and social integration. To this end, this study aims to evaluate the short-term effects of the newly developed anti-hate speech prevention program, "HateLess. Together against Hatred", on adolescents' empathy, self-efficacy, and counter-speech. Eight hundred and twenty adolescents between 12 and 16 (M = 13.27, SD = 1.04) from 11 German schools participated in this study. More specifically, 567 adolescents participated in the one-week prevention program, and 253 participants were assigned to the control group. Repeated measures ANOVAs showed that HateLess was successful, as there was a significant increase in empathy, self-efficacy, and counter-speech in the intervention group from the pretest (T1) to the posttest (T2) one month after the intervention. In contrast, no changes were found among adolescents in the control group. A multilevel mediation model revealed that the effect of being a member of the intervention group on counter-speech was partially mediated via empathy and self-efficacy. The findings indicate that HateLess is an effective, cost-efficient approach to enhance adolescents' counter-speech directly and indirectly by altering the skills they need to become informed citizens in democratic societies.

Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids.

Characterizing cell identity in complex tissues such as the human retina is essential for studying its development and disease. While retinal organoids derived from pluripotent stem cells have been widely used to model development and disease of the human retina, there is a lack of studies that have systematically evaluated the molecular and cellular fidelity of the organoids derived from various culture protocols in recapitulating their in vivo counterpart. To this end, we performed an extensive meta-atlas characterization of cellular identities of the human eye, covering a wide range of developmental stages. The resulting map uncovered previously unknown biomarkers of major retinal cell types and those associated with cell-type-specific maturation. Using our retinal-cell-identity map from the fetal and adult tissues, we systematically assessed the fidelity of the retinal organoids in mimicking the human eye, enabling us to comprehensively benchmark the current protocols for retinal organoid generation.

Epigenome-wide association study of BMI in Black populations from InterGEN and GENOA.

OBJECTIVE: Obesity is a significant public health concern across the globe. Research investigating epigenetic mechanisms related to obesity and obesity-associated conditions has identified differences that may contribute to cellular dysregulation that accelerates the development of disease. However, few studies include Black women, who experience the highest incidence of obesity and early onset of cardiometabolic disorders. METHODS: The association of BMI with epigenome-wide DNA methylation (DNAm) was examined using the 850K Illumina EPIC BeadChip in two Black populations (Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure [InterGEN], n = 239; and The Genetic Epidemiology Network of Arteriopathy [GENOA] study, n = 961) using linear mixed-effects regression models adjusted for batch effects, cell type heterogeneity, population stratification, and confounding factors. RESULTS: Cross-sectional analysis of the InterGEN discovery cohort identified 28 DNAm sites significantly associated with BMI, 24 of which had not been previously reported. Of these, 17 were replicated using the GENOA study. In addition, a meta-analysis, including both the InterGEN and GENOA cohorts, identified 658 DNAm sites associated with BMI with false discovery rate < 0.05. In a meta-analysis of Black women, we identified 628 DNAm sites significantly associated with BMI. Using a more stringent significance threshold of Bonferroni-corrected p value 0.05, 65 and 61 DNAm sites associated with BMI were identified from the combined sex and female-only meta-analyses, respectively. CONCLUSIONS: This study suggests that BMI is associated with differences in DNAm among women that can be identified with DNA extracted from salivary (discovery) and peripheral blood (replication) samples among Black populations across two cohorts.

The Impact of Language Discordance on Patients' Perception of a Clinical Encounter and Trust in Provider.

IMPORTANCE: The impact of language discordance on care for Spanish-speaking patients with pelvic floor disorders is unknown. OBJECTIVE: The aim of this study was to compare the impact of language concordance with the impact of language discordance on the patient experience and trust in their provider. METHODS: This cross-sectional cohort study enrolled English- and Spanish-speaking patients during initial evaluation in a urogynecology clinic. English- and Spanish-speaking patients seen by native English- or Spanish-speaking providers were recruited to the language-concordant group. The language-discordant group included Spanish-speaking patients seen with a translator or by nonnative Spanish-speaking providers. Patients completed the Trust in Physician Scale and the Consumer Assessment of Healthcare Providers and Systems Clinician and Group Survey (CG-CAHPS). Patients and providers rated the provider's Spanish proficiency on a 10-point scale from 0 (low) to 10 (high). Symptom bother questionnaires were completed 4-6 months after enrollment. RESULTS: Eighty women were recruited, with 40 in each group. Mean age was 55.4 ± 12.9 years. The majority identified as White (75%) and Hispanic (77.5%). Trust in Physician Scale scores were similar between groups (46.2 ± 8.5 vs 44.4 ± 7.5, P > 0.05). The provider communication, provider rating, and recommendation domains of the CG-CAHPS did not differ between groups (all P > 0.05). Provider self-rating of Spanish proficiency was lower than patient ratings (7.5 ± 1.8 vs 9.8 ± 0.5, P < 0.001). There was no difference between groups in symptom bother at 4-6 months (all P > 0.05). CONCLUSIONS: Patient-provider language discordance does not affect patient trust in the provider or perception of the encounter as measured by the Trust in Physician Scale and CG-CAHPS questionnaires.