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Background: The University of San Francisco, California (USFCA) and the Lesotho-Boston Health Alliance (LeBoHA) collaborated in designing and implementing an intensive, interprofessional global health immersion program for nursing and public health students from the United States. The program focused on health systems strengthening in Lesotho. This article reports on the curriculum development process, learning outcomes, and lessons learned from implementing the program. Methods: USFCA and LeBoHA began collaborating in March 2023. The partners codeveloped curriculum with the goal of introducing US students to global health systems challenges and ways to address them in a resource-constrained setting. The program sought to facilitate interprofessional collaboration between undergraduate nursing and graduate public health students, promote cross-cultural awareness and humility, and foster global perspectives and relationships to create a healthier and more humane world. The activity prioritized mutual respect in how the partner institutions worked together. Results: Three nursing and five public health students participated in the program held in January 2024 in Hlotse, Leribe District, Lesotho. The program included classroom learning sessions, health facility site visits, and extracurricular activities. Evaluation data suggested that students achieved course objectives and appreciated the active, experiential learning format. Lessons learned include planning for additional field visits and expanding the experience, possibly through Sesotho language instruction and interaction between students and LeBoHA faculty/staff before arrival and after the program ends. Conclusion: Short-term global health immersions can help to prepare nursing and public health students for careers in global health or working with underserved communities in the United States and strengthen interprofessionalism. Immersion programs should be developed in partnership and provide reciprocal benefits to the institutions involved.

BackgroundCardiovascular diseases (CVDs), including hypertension (HTN), have emerged among people living with HIV (PLHIV) as the most important prevalent contributors of non-AIDS-related mortality. Moreover, HTN itself is a modifiable risk factor for other CVDs. Data are limited regarding the prevalence of HTN and associated factors among PLHIV in Lesotho.AimTo determine the prevalence of HTN and associated factors among PLHIV attending Senkatana ART Clinic.SettingThe study was carried out at Senkatana ART Clinic in urban Maseru, Lesotho.MethodsA cross-sectional study was conducted from February to July 2022. Data were analysed using SAS statistical software (v9.4) and Microsoft Excel. To determine HTN prevalence, blood pressure (BP) was measured, and a questionnaire was administered to participants who were randomly selected using the lottery method from the clinic’s daily attendance list. Multiple logistic regression was used to assess factors associated with HTN in PLHIV while controlling for potentially confounding factors.ResultsThe prevalence of HTN was 57% (exact 95% CI: 51.2%, 62.7%). Of those with HTN, 33.3% were newly diagnosed during this study (exact 95% CI: 26.3%, 40.9%), while 69% of those previously diagnosed with HTN had uncontrolled HTN at enrollment (exact 95% CI: 60.0%, 77.6%). Age older than 50 years (p < 0.0001) and a body mass index (BMI) of 25.0 kg/m2 or higher (p < 0.0002) were independently associated with HTN.ConclusionHypertension was highly prevalent and poorly controlled. Factors associated with HTN in PLHIV were older age and higher BMI. The study’s findings support models of comprehensive healthcare delivery.

ObjectiveTo develop and implement a ‘low-dose, high-frequency’ (LDHF) advanced respiratory care training programme for COVID-19 care in Lesotho.DesignProspective pretraining–post-training evaluation.SettingLesotho has limited capacity in advanced respiratory care.ParticipantsPhysicians and nurses.InterventionsDue to limited participation in May–September 2020, the LDHF approach was modified into a traditional 1-day offsite training in November 2020 that reviewed respiratory anatomy and physiology, clinical principles for conventional oxygen, heated high-flow nasal cannula and non-invasive ventilation management. Basic mechanical ventilation principles were introduced.Outcome measuresParticipants completed a 20-question multiple choice examination immediately before and after the 1-day training. Paired t-tests were used to evaluate the difference in average participant pretraining and post-training examination scores.ResultsPretraining and post-training examinations were completed by 46/53 (86.7%) participants, of whom 93.4% (n=43) were nurses. The overall mean pretraining score was 44.8% (SD 12.4%). Mean scores improved by an average of 23.7 percentage points (95% CI 19.7 to 27.6, p<0.001) on the post-training examination to a mean score of 68.5% (SD 13.6%). Performance on basic and advanced respiratory categories also improved by 17.7 (95% CI 11.6 to 23.8) and 25.6 percentage points (95% CI 20.4 to 30.8) (p<0.001). Likewise, mean examination scores increased on the post-training test, compared with pretraining, for questions related to respiratory management (29.6 percentage points, 95% CI 24.1 to 35.0) and physiology (17.4 percentage points, 95% CI 12.0 to 22.8).ConclusionsAn LDHF training approach was not feasible during this early emergency period of the COVID-19 pandemic in Lesotho. Despite clear knowledge gains, the modest post-training examination scores coupled with limited physician engagement suggest healthcare workers require alternative educational strategies before higher advanced care like mechanical ventilation is implementable. Conventional and high-flow oxygen is better aligned with post-training healthcare worker knowledge levels and rapid implementation.

Control of atomic-scale interfaces between materials with distinct electronic structures is crucial for the design and fabrication of most electronic devices. In the case of two-dimensional materials, disparate electronic structures can be realized even within a single uniform sheet, merely by locally applying different vertical gate voltages. Here, we utilize the inherently nano-structured single layer and bilayer graphene on silicon carbide to investigate lateral electronic structure variations in an adjacent single layer of tungsten disulfide (WS 2 ). The electronic band alignments are mapped in energy and momentum space using angle-resolved photoemission with a spatial resolution on the order of 500 nm (nanoARPES). We find that the WS 2 band offsets track the work function of the underlying single layer and bilayer graphene, and we relate such changes to observed lateral patterns of exciton and trion luminescence from WS 2 . Sharp atomic interfaces between materials dictate the interface’s electronic properties. The authors use angle-resolved photoemission spectroscopy with a spatial resolution of ~500 nm to investigate the nanoscale electronic band structure and band alignment in a lateral heterostructure composed of WS 2 placed on alternating nano-stripes of monolayer and bilayer graphene.

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.

Significantly higher levels of plasma CXCL13 [chemokine (C-X-C motif) ligand 13] were associated with the generation of broadly neutralizing antibodies (bnAbs) against HIV in a large longitudinal cohort of HIV-infected individuals. Germinal centers (GCs) perform the remarkable task of optimizing B-cell Ab responses. GCs are required for almost all B-cell receptor affinity maturation and will be a critical parameter to monitor if HIV bnAbs are to be induced by vaccination. However, lymphoid tissue is rarely available from immunized humans, making the monitoring of GC activity by direct assessment of GC B cells and germinal center CD4+ T follicular helper (GC Tfh) cells problematic. The CXCL13–CXCR5 [chemokine (C-X-C motif) receptor 5] chemokine axis plays a central role in organizing both B-cell follicles and GCs. Because GC Tfh cells can produce CXCL13, we explored the potential use of CXCL13 as a blood biomarker to indicate GC activity. In a series of studies, we found that plasma CXCL13 levels correlated with GC activity in draining lymph nodes of immunized mice, immunized macaques, and HIV-infected humans. Furthermore, plasma CXCL13 levels in immunized humans correlated with the magnitude of Ab responses and the frequency of ICOS⁺ (inducible T-cell costimulator) Tfh-like cells in blood. Together, these findings support the potential use of CXCL13 as a plasma biomarker of GC activity in human vaccine trials and other clinical settings.

Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that have integrated into the human genome. Using publicly available RNA-seq data from 63 cervical cancer patients, we investigated the expression of ERVs in cervical cancers. Four aspects of cervical cancer were investigated: patient ancestral background, tumor HPV type, tumor stage and patient survival. Between the racial subgroups, 74 ERVs were significantly differentially expressed, with Black Americans having 30 upregulated and 44 downregulated (including MER21C, HERV9-int, and HERVH-int) ERVs when compared to White Americans. We found that 3313 ERVs were differentially expressed between HPV subgroups, including MER41A, HERVH-int and HERVK9. There were 28 downregulated (including MLT1D and HERVH-int) and 61 upregulated (including MER41A) ERVs in locally advanced-stage compared to early-stage samples. Tissue microarrays of cervical cancer patients were used to investigate the protein expression of ERVs with protein coding potential (i.e., HERVK and ERV3). Significant differences in protein expression of ERV3 (p = 0.000905) were observed between early-stage and locally advanced-stage tumors. No significant differential expression at the protein level was found for HERVK7 (p = 0.243). We also investigated a prognostic model, supplementing a baseline prediction model using FIGO stage, age and HPV positivity with ERVs data. The expression levels of all ERVs in the HERVd were input into a Lasso-Cox proportional hazards model, developing a predictive 67-ERV panel. When ERVs expression levels were supplemented with the clinical data, a significant increase in prognostic power (p = 9.433 × 10−15) relative to that obtained with the clinical parameters alone (p = 0.06027) was observed. In summary, ERV RNA expression in cervical cancer tumors is significantly different among racial cohorts, HPV subgroups and disease stages. The combination of the expression of certain ERVs in cervical cancers with clinical factors significantly improved prognostication compared to clinical factors alone; therefore, ERVs may serve as future prognostic biomarkers and therapeutic targets. Novelty and Impact: When endogenous retroviral (ERV) expression signatures were combined with currently employed clinical prognosticators of relapse of cervical cancer, the combination outperformed prediction models based on clinical prognosticators alone. ERV expression signatures in tumor biopsies may therefore be useful to help identify patients at greater risk of recurrence. The novel ERV expression signatures or adjacent genes possibly impacted by ERV expression described here may also be targets for the development of future therapeutic interventions.

To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type–specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C , SATB2 , SOX5 , TCF4 , and TSHZ3 ) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.