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As a high-impact educational practice, service-learning has demonstrated success in positively influencing students' overall development, and much work has been done on investigating student learning outcomes from service-learning. A particular direction is to model students' learning outcomes in the context of their learning experience, i.e., the various student, course, and pedagogical elements. It contributes to a better understanding of the learning process, a more accurate prediction of students' attainments on the learning outcomes, and improvements in the design of learning activities to maximize student learning. However, most of the existing work in this area relies on statistical analysis that makes assumptions about attribute independence or simple linear dependence, which may not accurately reflect real-life scenarios. In contrast, the study described in this paper adopted a neural network-based approach to investigate the impact of students' learning experience on different service-learning outcomes. A neural network with attention mechanisms was constructed to predict students' service-learning outcomes by modeling the contextual information from their various learning experiences. In-depth evaluation experiments on a large-scale dataset collected from more than 10,000 students showed that this proposed model achieved better accuracy on predicting service-learning outcomes. More importantly, it could capture the interdependence between different aspects of student learning experience and the learning outcomes. We believe that this framework can be extended to student modeling for other types of learning activities.

Chan, Stephen. 2011. SOUTHERN AFRICA: OLD TREACHERIES AND NEW DECEITS. New Haven and London: Yale University Press. 302 pp. In a new book, Southern Africa: Old Treacheries and New Deceits, [...]

Service-learning has become widespread in universities worldwide, implying an increased number of involved faculty. Many studies document service-learning's impact on students, but only a handful of exploratory studies examine impact on faculty. We offer a focused investigation of positive and negative impacts of service-learning on faculty from an Asian context, based on interviews with 24 faculty members from diverse academic disciplines in a university in Hong Kong. Phenomenological methods are used to summarize the essences of firsthand experiences. Participants' valenced views about service-learning's impact are categorized as dominant positive, mixed, and negative stances. Service-learning contributed to faculty teaching, civic-mindedness, person/values, professional development, and research. Findings suggest that service-learning involvement can benefit more diverse faculty than previously identified. Service-learning is recommended as a strategy for faculty development, and as a means for universities to fulfill their social responsibility and contribute to sustainable development goals outlined by the United Nations.

The 2019/2020 academic year brought historic opportunities for faculty to manage virtual exchanges (O'Dowd, 2021), yet limited research exists on how teachers develop their capacity within these programs. As educators collaborating on a transnational virtual exchange, we aim to investigate the process that teachers go through as they co-develop and collaborate in a transnational virtual exchange from our experiences and perceptions. We ask: To what extent do previous lived experiences mediate the process of teacher capacity building in a transnational virtual, collaborative exchange? This collaborative qualitative autoethnography case study explores our experiences as four instructors from the United States and Hong Kong, reflecting our experiences as they relate to teacher capacity building in transnational virtual exchange. The data suggests that previously lived international experiences assisted the instructors in capacity building within a virtual exchange and brought into question the role of cultural humility.

Background Pulmonary arterial hypertension (PAH) is a complex, fatal disease where disease severity has been associated with the single nucleotide polymorphism (SNP) rs2856830, located near the human leukocyte antigen DPA1 (HLA-DPA1) gene. We aimed to define the genetic architecture of functional variants associated with PAH disease severity by identifying allele-specific binding transcription factors and downstream targets that control endothelial pathophenotypes and PAH. Methods and Results Electrophoretic mobility shift assays of oligonucleotides containing SNP rs2856830 and 8 SNPs in linkage disequilibrium revealed functional SNPs via allele-imbalanced binding to human pulmonary arterial endothelial cell nuclear proteins. DNA pulldown proteomics identified SNP-binding proteins. SNP genotyping and clinical correlation analysis were performed in 84 patients with PAH at University of Pittsburgh Medical Center and in 679 patients with PAH in the All of Us database. SNP rs9277336 was identified as a functional SNP in linkage disequilibrium (r2>0.8) defined by rs2856830, and the minor allele was associated with decreased hospitalizations and improved cardiac output in patients with PAH, an index of disease severity. SNP pulldown proteomics showed allele-specific binding of nuclear ACTN4 (alpha actinin 4) protein to rs9277336 minor allele. Both ACTN4 and HLA-DPA1 were downregulated in pulmonary endothelium in human patients and rodent models of PAH. Via transcriptomic and phenotypic analyses, knockdown of HLA-DPA1 phenocopied knockdown of ACTN4, both similarly controlling cell structure pathways, immune pathways, and endothelial dysfunction. Conclusions We defined the pathogenic activity of functional SNP rs9277336, entailing the allele-specific binding of ACTN4 and controlling expression of the neighboring HLA-DPA1 gene. Through inflammatory or genetic means, downregulation of this ACTN4-HLA-DPA1 regulatory axis promotes endothelial pathophenotypes, providing a mechanistic explanation for the association between this SNP and PAH outcomes.

Pulmonary arterial hypertension (PAH) features pathogenic and abnormal endothelial cells (ECs), and one potential origin is clonal selection. We studied the role of p53 and toll-like receptor 3 (TLR3) in clonal expansion and pulmonary hypertension (PH) via regulation of bone morphogenetic protein (BMPR2) signaling. ECs of PAH patients had reduced p53 expression. EC-specific p53 knockout exaggerated PH, and clonal expansion reduced p53 and TLR3 expression in rat lung CD117+ ECs. Reduced p53 degradation (Nutlin 3a) abolished clonal EC expansion, induced TLR3 and BMPR2, and ameliorated PH. Polyinosinic/polycytidylic acid [Poly(I:C)] increased BMPR2 signaling in ECs via enhanced binding of interferon regulatory factor-3 (IRF3) to the BMPR2 promoter and reduced PH in p53-/- mice but not in mice with impaired TLR3 downstream signaling. Our data show that a p53/TLR3/IRF3 axis regulates BMPR2 expression and signaling in ECs. This link can be exploited for therapy of PH.

Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.

AmeriFlux is a network of research sites that measure carbon, water, and energy fluxes between ecosystems and the atmosphere using the eddy covariance technique to study a variety of Earth science questions. AmeriFlux's diversity of ecosystems, instruments, and data-processing routines create challenges for data standardization, quality assurance, and sharing across the network. To address these challenges, the AmeriFlux Management Project (AMP) designed and implemented the BASE data-processing pipeline. The pipeline begins with data uploaded by the site teams, followed by the AMP team's quality assurance and quality control (QA/QC), ingestion of site metadata, and publication of the BASE data product. The semi-automated pipeline enables us to keep pace with the rapid growth of the network. As of 2022, the AmeriFlux BASE data product contains 3,130 site years of data from 444 sites, with standardized units and variable names of more than 60 common variables, representing the largest long-term data repository for flux-met data in the world. The standardized, quality-ensured data product facilitates multisite comparisons, model evaluations, and data syntheses.

BackgroundThe prognosis and therapeutic responses are worse for pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) compared with idiopathic pulmonary arterial hypertension (IPAH). This discrepancy could be driven by divergence in underlying metabolic determinants of disease.Research questionAre circulating bioactive metabolites differentially altered in SSc-PAH vs IPAH, and can this alteration explain clinical disparity between these PAH subgroups?Study design and methodsPlasma biosamples from 400 patients with SSc-PAH and 1,082 patients with IPAH were included in the study. Another cohort of 100 patients with scleroderma with no PH and 44 patients with scleroderma with PH was included for external validation. More than 700 bioactive lipid metabolites, representing a range of vasoactive and immune-inflammatory pathways, were assayed in plasma samples from independent discovery and validation cohorts using liquid chromatography/high-resolution mass spectrometry-based approaches. Regression analyses were used to identify metabolites that exhibited differential levels between SSc-PAH and IPAH and associated with disease severity.ResultsFrom hundreds of circulating bioactive lipid molecules, five metabolites were found to distinguish between SSc-PAH and IPAH, as well as associate with markers of disease severity. Relative to IPAH, patients with SSc-PAH carried increased levels of fatty acid metabolites, including lignoceric acid and nervonic acid, as well as eicosanoids/oxylipins and sex hormone metabolites.InterpretationPatients with SSc-PAH are characterized by an unfavorable bioactive metabolic profile that may explain the poor and limited response to therapy. These data provide important metabolic insights into the molecular heterogeneity underlying differences between subgroups of PAH.

Background: The context of learning, which includes the host country, is an important variable of service-learning. Since international service-learning programs often take place in developing countries, studies about their impact and outcomes commonly draw from experiences in developing countries. Purpose: We investigate service-learning experience in developed, urban settings focusing on dissonances and civic outcomes, key areas of service-learning pedagogy. Methodology/Approach: This an instrumental case study based on a small group sample of 12 Asian student participants of a service-learning exchange to partner universities in the USA. Findings/Conclusions: Findings suggest that developed cities can be fertile grounds for impactful dissonances and civic learning. "First-world expectations" increased or intensified dissonances students experienced. Confronting urban poverty and other social issues in cities similar to their own led students to see domestic problems with fresh eyes. Implications: Service-learning exchange in developed cities can facilitate understanding social problems particularly in the way these occur in developed countries and promises transferability of learning. However, students need prompting to connect experiences overseas to home contexts and draw practical consequences. Faculty or staff assistance is necessary to help students constructively cope with powerful dissonances.

BackgroundMany patients with heart failure with preserved ejection fraction have metabolic syndrome and develop exercise-induced pulmonary hypertension (EIPH). Increases in pulmonary vascular resistance in patients with heart failure with preserved ejection fraction portend a poor prognosis; this phenotype is referred to as combined precapillary and postcapillary pulmonary hypertension (CpcPH). Therapeutic trials for EIPH and CpcPH have been disappointing, suggesting the need for strategies that target upstream mechanisms of disease. This work reports novel rat EIPH models and mechanisms of pulmonary vascular dysfunction centered around the transcriptional repression of the soluble guanylate cyclase (sGC) enzyme in pulmonary artery (PA) smooth muscle cells.MethodsWe used obese ZSF-1 leptin-receptor knockout rats (heart failure with preserved ejection fraction model), obese ZSF-1 rats treated with SU5416 to stimulate resting pulmonary hypertension (obese+sugen, CpcPH model), and lean ZSF-1 rats (controls). Right and left ventricular hemodynamics were evaluated using implanted catheters during treadmill exercise. PA function was evaluated with magnetic resonance imaging and myography. Overexpression of nuclear factor Y α subunit (NFYA), a transcriptional enhancer of sGC β1 subunit (sGCβ1), was performed by PA delivery of adeno-associated virus 6. Treatment groups received the SGLT2 inhibitor empagliflozin in drinking water. PA smooth muscle cells from rats and humans were cultured with palmitic acid, glucose, and insulin to induce metabolic stress.ResultsObese rats showed normal resting right ventricular systolic pressures, which significantly increased during exercise, modeling EIPH. Obese+sugen rats showed anatomic PA remodeling and developed elevated right ventricular systolic pressure at rest, which was exacerbated with exercise, modeling CpcPH. Myography and magnetic resonance imaging during dobutamine challenge revealed PA functional impairment of both obese groups. PAs of obese rats produced reactive oxygen species and decreased sGCβ1 expression. Mechanistically, cultured PA smooth muscle cells from obese rats and humans with diabetes or treated with palmitic acid, glucose, and insulin showed increased mitochondrial reactive oxygen species, which enhanced miR-193b-dependent RNA degradation of nuclear factor Y α subunit (NFYA), resulting in decreased sGCβ1-cGMP signaling. Forced NYFA expression by adeno-associated virus 6 delivery increased sGCβ1 levels and improved exercise pulmonary hypertension in obese+sugen rats. Treatment of obese+sugen rats with empagliflozin improved metabolic syndrome, reduced mitochondrial reactive oxygen species and miR-193b levels, restored NFYA/sGC activity, and prevented EIPH.ConclusionsIn heart failure with preserved ejection fraction and CpcPH models, metabolic syndrome contributes to pulmonary vascular dysfunction and EIPH through enhanced reactive oxygen species and miR-193b expression, which downregulates NFYA-dependent sGCβ1 expression. Adeno-associated virus-mediated NFYA overexpression and SGLT2 inhibition restore NFYA-sGCβ1-cGMP signaling and ameliorate EIPH.

The dynamic regulation of endothelial pathophenotypes in pulmonary hypertension (PH) remains undefined. Cellular senescence is linked to PH with intracardiac shunts; however, its regulation across PH subtypes is unknown. Since endothelial deficiency of iron-sulfur (Fe-S) clusters is pathogenic in PH, we hypothesized that a Fe-S biogenesis protein, frataxin (FXN), controls endothelial senescence. An endothelial subpopulation in rodent and patient lungs across PH subtypes exhibited reduced FXN and elevated senescence. In vitro, hypoxic and inflammatory FXN deficiency abrogated activity of endothelial Fe-S-containing polymerases, promoting replication stress, DNA damage response, and senescence. This was also observed in stem cell-derived endothelial cells from Friedreich's ataxia (FRDA), a genetic disease of FXN deficiency, ataxia, and cardiomyopathy, often with PH. In vivo, FXN deficiency-dependent senescence drove vessel inflammation, remodeling, and PH, whereas pharmacologic removal of senescent cells in Fxn-deficient rodents ameliorated PH. These data offer a model of endothelial biology in PH, where FXN deficiency generates a senescent endothelial subpopulation, promoting vascular inflammatory and proliferative signals in other cells to drive disease. These findings also establish an endothelial etiology for PH in FRDA and left heart disease and support therapeutic development of senolytic drugs, reversing effects of Fe-S deficiency across PH subtypes.

To assess whether primary care medical homes (PCMHs) are accurately identified for patients receiving care in a specialty mental health clinic within an integrated public delivery system. This study reviewed the electronic records of patients in a large urban mental health clinic. The study defined 'matching PCMH' if the same primary care clinic was listed in both the mental health and medical electronic records. This study designated all others as 'PCMH unknown.' This study assessed whether demographic factors predicted PCMH status using chi-square tests. Among 229 patients (66% male; mean age 49; 36% White, 30% Black, and 17% Asian), 72% had a matching PCMH. Sex, age, race, psychiatric diagnosis, and psychotropic medication use were not associated with matching PCMH. To improve care coordination and health outcomes for people with severe mental illness, greater efforts are needed to ensure the accurate designation of PCMHs in all mental health patient electronic records.