William Penn University

Obstructive sleep apnea (OSA) is increasingly recognized as a major comorbidity in chronic respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). The coexistence of OSA with asthma or COPD significantly complicates the clinical course, leading to poorer disease control, more frequent exacerbations, reduced lung function, impaired sleep quality, and increased cardiovascular and overall mortality. In asthma, OSA exacerbates airway inflammation, enhances bronchial hyperresponsiveness, and decreases responsiveness to standard therapies. In COPD, the “overlap syndrome” is associated with profound nocturnal hypoxemia, chronic hypercapnia, pulmonary hypertension, and a markedly elevated risk of hospitalization and death. Underlying mechanisms include chronic airway inflammation, oxidative stress induced by intermittent hypoxia, instability of ventilatory control (high loop gain), structural upper-airway alterations, and the burden of obesity and metabolic dysfunction. These interactions highlight the urgent need for integrated and proactive management strategies. Thus, we propose an Asthma–COPD–OSA Outpatient Unit (ACOSOU)—a care-delivery model, not a disease entity—designed to integrate systematic screening, diagnosis, treatment initiation, and long-term follow-up of OSA in patients with asthma and COPD. Optimal care requires systematic screening in respiratory outpatient settings, appropriate diagnostic pathways using polysomnography or home sleep apnea testing, and individualized treatment approaches. Continuous positive airway pressure (CPAP) remains the cornerstone therapy for OSA–asthma and OSA–COPD overlap, improving gas exchange, reducing exacerbations, and enhancing disease control. Comprehensive management also includes optimization of inhaled therapies, pulmonary rehabilitation, weight reduction, sleep hygiene, and multidisciplinary collaboration. This review proposes an integrated ACOSOU model to streamline screening, diagnosis, CPAP titration, and long-term follow-up. However, implementation in low- and middle-income countries faces challenges including limited trained sleep-medicine personnel, unequal access to diagnostic tools, and high CPAP costs without insurance coverage. Strengthening infrastructure, training, and policy support will be essential to improve outcomes for patients with chronic respiratory diseases and OSA comorbidity.

Abstract Poly (ADP-Ribose) Polymerase inhibitors (PARPi) induce cytotoxicity in homologous recombination repair (HRR)-deficient cancers by causing PARP1 to become trapped on chromatin, resulting in irreparable replication-associated DNA damage. Although increased clearance of trapped PARP1 from chromatin reduces the sensitivity of cancer cells to PARPi, details surrounding this process remain unclear. PARPi exposure is known to cause increased autophagy flux, whilst autophagy inhibition can hypersensitise cells to PARPi. Using various biochemical, cell biological and live imaging-based assays, we found that trapped PARP1 is cleared by nucleophagy, the selective autophagy of nuclear substrates. Specifically, the nucleophagy of trapped PARP1 was orchestrated by the selective autophagy receptor TEX264 and its partner segregase p97/VCP. TEX264 mediates this process by directly interacting with trapped PARP1, thus bridging PARP1 to the autophagosomal resident protein LC3 for processing via autophagy. Impeding this process, either chemically or genetically, heightened PARP1 trapping, leading to accumulation of protein aggregates, replication-associated DNA damage and cell lethality, re-sensitising PARPi-resistant cells to various PARPi. In conclusion, we show that nucleophagy acts in a cytoprotective manner to directly target PARPi-induced trapped PARP1 for degradation.

ABSTRACT Social media platforms often prioritize engagement metrics that amplify outrage and self-promotion, fostering environments of toxicity and hubris rather than humility. Despite the critical role humility plays in ethical formation and intellectual flourishing, its integration into digital media ethics remains underexplored. This project explores humility’s role in digital media ethics, integrating insights from psychology, virtue epistemology, and virtue ethics. Research shows humility is correlated with curiosity, reflection, and openness to opposing views, all critical traits for fostering civil discourse. Philosophical and empirical studies further underscore humility as a multidimensional virtue, requiring an accurate self-assessment, an orientation toward others, and the ability to quiet personal biases to perceive broader realities. We argue that cultivating humility in digital contexts demands deliberate strategies, including heightened self-awareness, perspective-taking, and attentiveness to others. This project suggests that fostering humility-related behaviors online can transform digital spaces into environments conducive to collective well-being and ethical engagement.

We previously identified Paenibacillus species in the cerebrospinal fluid of 44% of infants presenting for neurosurgical evaluation with findings consistent with postinfectious hydrocephalus (PIH) in Eastern Uganda. Here we sought to compare outcomes among hydrocephalic infants with and without Paenibacillus detection at the time of hydrocephalus surgery. In a prospective observational study, 78 infants with PIH who underwent a cerebrospinal fluid (CSF) diversion prior to 90 days of age had a positive CSF polymerase chain reaction result for Paenibacillus species (PP), and 111 had a negative result (PN). The primary outcome was diversion failure-free survival defined as being alive without diversion failure at last patient contact. Secondary outcomes included overall survival and diversion success. After a median follow-up period of 35.7 months, the primary outcome was observed in 42 PP patients (54%) and in 76 PN patients (68%) (adjusted hazard ratio (aHR), 2.45; 95% confidence interval [CI], 1.42 to 4.22; P=0.001). PP patients who underwent endoscopic diversion had the worst primary event rate (aHR, 6.47; 95% CI, 2.40 to 17.42; P<0.001). Death from any cause occurred in 16 PP patients (20%) and 9 PN patients (8%) (aHR, 3.47; 95% CI, 1.44 to 8.37; P=0.006). Diversion failure occurred in 28 PP patients (36%) and in 29 PN patients (26%) (aHR, 2.24; 95% CI, 1.31 to 3.85; P=0.003). In this study, Paenibacillus detection in the CSF at the time of hydrocephalus surgery was associated with a significantly increased rate of the composite of diversion failure or death, death, and diversion failure, and was particularly increased for patients who had an endoscopic diversion.

Advocacy is important in educator preparation programs, equipping future teachers with the knowledge, skills, and mindset to support students, schools, and communities. Educators are critical in driving policy change and supporting students with disabilities. This article explores how educator preparation programs can engage in advocacy at the local, state, and federal levels. The authors share strategies and insights for involving undergraduate and graduate students in advocacy work within communities and local school districts and building relationships with key stakeholders at the state and federal levels. By prioritizing advocacy, educator preparation programs encourage future teachers to actively engage with the broader educational ecosystem, collaborate with stakeholders, and become change agents in schools and communities.

Abstract Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) has become a powerful tool for dissecting the causal relationships between exposure and outcomes. As GWAS begins to incorporate samples of diverse ancestries, the optimal strategy to perform MR analysis integrating these GWAS results remains to be determined. To fill in this gap, we proposed a robust method that aggregates the genetic variant–risk factor association summary statistics of multiple ancestries by modelling the genetic effects of the exposure as a function of the principal components of genome-wide allele frequency. This allows borrowing information from different ancestry groups and accounting for potential between-ancestry heterogeneities. The method is general and can be used with different MR methods. We demonstrated that our method improves accuracy and power compared to the inverse-variance weighting method based on only ancestry-stratified samples, with additional benefits in correcting winner’s curse bias. We also illustrated the flexibility and potential of discovering novel causal genes for autoimmune disease traits of our method in practice.

Objective: This study aimed to demonstrate the accuracy of a portable device for measuring nasal and bronchial fractional exhaled nitric oxide (nFeNO and FeNO) as an alternative method to replace a high-cost multiple flow device in subjects with allergic rhinitis (AR) . Methods: It was a descriptive and comparative study. The healthy subjects (control group), subjects with AR (AR group) and those with AR and asthma (AR-A group) were enrolled in this study. They underwent nasal and bronchial FeNO measurements by both fixed flow NObreath ® connected to nasal mask (for nFeNO) and without mask (for FeNO) and multiple flows HypAir FeNO ® . Results: There were 153 subjects recruited during the study period, including 63 healthy subjects and 90 subjects with AR and AR-A. There were no statistically significant differences in anthropometric characteristics between study groups. The concentrations of nasal FeNO and bronchial FeNO measured by a portable device in subjects with AR were higher than in healthy subjects: 76.0 ± 50.7 ppb vs 36.0 ± 28.1 ppb ( P &lt; 0.01), and 32.3 ± 15.4 ppb vs 9.2 ± 5.6 ppb ( P &lt; 0.001). There was a weak correlation between nasal FeNO measured by portable devices and multiple flow devices. Conclusions: The portable device is useful in measuring nasal FeNO in subjects with AR. The advantages of a low-cost and accurate portable device may help it be used in primary care in the management of subjects with allergic rhinitis and asthma

Agricultural workers are subjected to various challenges in the workplace, including inequitable employment arrangements, dangerous working conditions, and low wages.Employers abuse their authority by using coercive labor practices and taking advantage of flawed laborer protection laws to maximize profits at the expense of laborers.This paper reviews the history of agricultural labor working conditions and prison labor laws to examine potential solutions to these injustices.In addition to providing a historical context on agricultural labor, this paper offers a multi-modal review of primary material, existing U.S. laws and domestic and foreign policy, current academic research, population statistics, and organizations seeking change regarding agricultural labor violations.Ultimately, through this review, this paper concludes with suggestive Fair Trade policy augmentations that can be used to improve working conditions and reduce abuses for agricultural laborers.

Abstract Social media has altered how humans express emotions, among them, grief. Features unique to social media platforms, such as persistence, replicability, scalability, and searchability have afforded social media users new spaces and larger communities in which to express deep, complex pain and find support. This interdisciplinary study, leveraging insights from social work, computer science, and linguistics, explores how grief and daily stressors are expressed, on a digital platform, among Black Harlem residents and students attending a large university in New York City. Particular attention is given to posts with features that reflect African American English and social media-specific language, seeking to understand challenges associated with interpreting these expressions; misinterpretation can lead to differential support and treatment for those seeking help. To examine the experience, we created the Integrating Emotional Stories Online (IESO) platform, to collect expressions of grief and everyday stress. The platform allowed participants to anonymously post and self-label their emotions; we analyzed posts using qualitative and computational topic modeling methods to identify core themes. We identified four primary themes: expressions of interpersonal grief, systemic grief, everyday stressors and self-care &amp; joy. The computational topic modeling approach validated those themes. The study was conducted in the context of significant events such as the COVID-19 pandemic, protests against police brutality, and mass shootings. Findings reveal the complex ways grief and everyday stress may be communicated in digital space, emphasizing the importance of deep analysis and reflection when examining hyper-local dialects. Findings also underscore the importance of digital platforms in understanding and supporting individuals who experience grief and other forms of stress, providing valuable insights for mental health practitioners.