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Correction to: Nature Communicationshttps://doi.org/10.1038/s41467-024-45998-2, published online 26 February 2024 In the Acknowledgements section of this article, the grant number relating to National Institutes of Health funding to J.A.D. was incorrectly given as RM1HG009490 and should have been U19NS132303. The grant number 2334028 relating to the National Science Foundation funding to J.A.D. was omitted. Funding from Hampton University Summer Undergraduate Research Program, Mr. Li Ka Shing, Emerson Collective and the Innovative Genomics Institute (IGI) were omitted. The original article has been corrected.

The delivery of CRISPR ribonucleoproteins (RNPs) for genome editing in vitro and in vivo has important advantages over other delivery methods, including reduced off-target and immunogenic effects. However, effective delivery of RNPs remains challenging in certain cell types due to low efficiency and cell toxicity. To address these issues, we engineer self-deliverable RNPs that can promote efficient cellular uptake and carry out robust genome editing without the need for helper materials or biomolecules. Screening of cell-penetrating peptides (CPPs) fused to CRISPR-Cas9 protein identifies potent constructs capable of efficient genome editing of neural progenitor cells. Further engineering of these fusion proteins establishes a C-terminal Cas9 fusion with three copies of A22p, a peptide derived from human semaphorin-3a, that exhibits substantially improved editing efficacy compared to other constructs. We find that self-deliverable Cas9 RNPs generate robust genome edits in clinically relevant genes when injected directly into the mouse striatum. Overall, self-deliverable Cas9 proteins provide a facile and effective platform for genome editing in vitro and in vivo.

Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9. The production of ultra-low endotoxin Cas9 protein manufactured at scale further improved innate immunity. We conclude that injection-based delivery of minimally immunogenic CRISPR genome editing RNPs into the CNS provides a valuable alternative to virus-mediated genome editing.

BackgroundPublic health pandemics, such as COVID-19, not only impact the physical health and wellbeing of communities but also often have far-reaching effects on their social, psychological, environmental, and economic welfare. The coronavirus pandemic has highlighted the significant inequities experienced among those who are Black, Indigenous, and People of Color (BIPOC), especially in the areas of housing instability, unemployment, and debt accrual. This study investigates the socioeconomic impacts of COVID-19 on residents of the Canal neighborhood ("The Canal"), a low-income Latinx community in Marin County, California. This study also uplifts mitigation strategies already underway to facilitate post-pandemic recovery efforts.MethodsThis study utilized a mixed-methods, community participatory approach in which community leaders from a local nonprofit, Canal Alliance, administered a survey assessing the impact of COVID-19 on Canal residents. Additionally, community stakeholders including nonprofits, small businesses, and public officials were interviewed, and their field notes were analyzed through exploratory open coding.ResultsOn a macro level, the data showed that Canal residents were severely impacted by COVID-19 in the form of massive job loss (61.2% of respondents were unemployed or underemployed) as well as financial stress related to eviction, housing instability, and debt accrual (78.8% of respondents struggled to cover rent and often had to borrow money from friends and family).ConclusionsIn spite of the severe socioeconomic impacts of COVID-19 on The Canal, there is a significant opportunity for recovery and growth because of an overwhelming investment by residents, community-based organizations, and public officials to support those who have been financially impacted by the pandemic. Some key areas of policy focus include expansion of affordable housing, pandemic-resistant workforce development, and restructuring of social services to increase accessibility. This report will explore recommendations related to strategic funding of community-based programs as well as short-term and long-term solutions for economic recovery.

The Thousand Talents Plan was an ambitious government initiative to repatriate and/or recruit experts from the global Chinese diaspora, along with some non-Chinese experts. The plan has received much criticism from abroad, accusing it of taking advantage of the open international education sector and facilitating espionage. While the Thousand Talents Plan received the most international attention, it was just one of over 200 Chinese governmental talent recruitment plans, which we label broadly as the Thousand Talents Brand (TTB). Using bibliometric analysis from the Web of Science, we find that research connected to the TTB decreased following the recent outcry but was only roughly 1% of all Chinese research output at its peak in 2018. We also find that the research was mostly concentrated in the hard sciences, with relatively little in the social sciences. Our results show the research funded through the initiatives was most partnered with researchers from the Western powers, including connections to institutions with national security concerns. While the findings do illustrate a complex web of global research governance through international partnerships, they cannot alleviate scrutiny of the potential alignment between the TTB programs and sensitive sectors abroad.

The attacks of September 11, 2001, put terrorism at the forefront of the American political landscape. Donald Trump played into these fears of terrorism through his political rhetoric during his presidency, particularly targeting international students as "threats" to the nation. However, we argue that the labeling of international students as security threats was not started after 9/11 nor invented by Trump. Through historical records and accounts across decades of policies related to this issue, we seek to answer two questions: How has the U.S. government monitored visa policies and programs for international students? How have U.S. national policies evolved to view international students as national security threats? We found that mistrust of this population has been embedded throughout U.S. immigration history and that federal tracking policies emerged incrementally from long-held security concerns. The essay closes with a discussion on why the entire population of international students should not be scapegoated due to these fears.

Determining eligibility for the special education category Emotional Disturbance (ED) is a challenging task. The difficulty in identifying students with ED is due, in part, to problematic federal criteria (Olympia et al., 2004; Skiba, Grizzle, & Minke, 1994). Unchanges since 1975, these criteria have created an environment in which inconsistent assessment practices and diagnostic decisions are inevitable. The current study examines school psychologists' ED assessment practices, and in particular, the use of projective assessment techniques in eligibility determinations. The results suggest that school psychologists regularly use these controversial diagnostic techniques despite questions regarding their psychometric soundness (i.e., reliability and validity) and utility. Among the projective measures reported, those with the most limited empirical support (e.g., H-T-P, KFDS) were most widely used.

The concept of the world-class university has proliferated throughout the world, yet there is no universal consensus on how to define these elite institutions. Without a unified definition, rankings have become a direct proxy for sense-making in the sector and a commensurate indicator that decision-makers have used to understand the world-class concept. Through interviews with 48 informants from the Chinese higher education sector, I explore how institutions in China conceptualise world-class status through university rankings. First, I show that the sector in China has intently focused on league table positioning, with the top-100 as a popular cut-off point for guaranteed world-class status. Next, I explore which global rankings have been the most influential -- QS, "THE," ARWU, and "US News." Finally, I discuss how actors living in this competitive higher education environment have altered research agendas and institutional partnerships to align with global ranking metrics.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

Idiopathic pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of surfactant. Surfactant synthesis and secretion are restricted to epithelial type 2 (T2) pneumocytes (also called T2 cells). Clearance of surfactant is dependent upon T2 cells and macrophages. ABCG1 is highly expressed in both T2 cells and macrophages. ABCG1-deficient mice accumulate surfactant, lamellar body-loaded T2 cells, lipid-loaded macrophages, B-1 lymphocytes, and immunoglobulins, clearly demonstrating that ABCG1 has a critical role in pulmonary homeostasis. We identify a variant in the ABCG1 promoter in patients with PAP that results in impaired activation of ABCG1 by the liver X receptor α, suggesting that ABCG1 basal expression and/or induction in response to sterol/lipid loading is essential for normal lung function. We generated mice lacking ABCG1 specifically in either T2 cells or macrophages to determine the relative contribution of these cell types on surfactant lipid homeostasis. These results establish a critical role for T2 cell ABCG1 in controlling surfactant and overall lipid homeostasis in the lung and in the pathogenesis of human lung disease.

BackgroundIncome, air pollution, obesity, and smoking are primary factors associated with human health and longevity in population-based studies. These four factors may have countervailing impacts on longevity. This analysis investigates longevity trade-offs between air pollution and income, and explores how relative effects of income and air pollution on human longevity are potentially influenced by accounting for smoking and obesity.MethodsCounty-level data from 2,996 U.S. counties were analyzed in a cross-sectional analysis to investigate relationships between longevity and the four factors of interest: air pollution (mean 1999-2008 PM2.5), median income, smoking, and obesity. Two longevity measures were used: life expectancy (LE) and an exceptional aging (EA) index. Linear regression, generalized additive regression models, and bivariate thin-plate smoothing splines were used to estimate the benefits of living in counties with higher incomes or lower PM2.5. Models were estimated with and without controls for smoking, obesity, and other factors.ResultsModels which account for smoking and obesity result in substantially smaller estimates of the effects of income and pollution on longevity. Linear regression models without these two variables estimate that a $1,000 increase in median income (1 μg/m(3) decrease in PM2.5) corresponds to a 27.39 (33.68) increase in EA and a 0.14 (0.12) increase in LE, whereas models that control for smoking and obesity estimate only a 12.32 (20.22) increase in EA and a 0.07 (0.05) increase in LE. Nonlinear models and thin-plate smoothing splines also illustrate that, at higher levels of income, the relative benefits of the income-pollution tradeoff changed-the benefit of higher incomes diminished relative to the benefit of lower air pollution exposure.ConclusionsHigher incomes and lower levels of air pollution both correspond with increased human longevity. Adjusting for smoking and obesity reduces estimates of the benefits of higher income and lower air pollution exposure. This adjustment also alters the tradeoff between income and pollution: increases in income become less beneficial relative to a fixed reduction in air pollution-especially at higher levels of income.

While academics and university administrators often criticize rankings, league tables have become important tools for student decision-making, especially in the Chinese sector. Yet, research has not fully explored how students in China have engaged with both global and local rankings, as most studies have focused on one setting or the other. Likewise, researchers have not tested students' knowledge of rankings, despite the intense focus on these actors by universities. Using a survey of over 900 students from Chinese universities, the author explored how knowledge of rankings varies in different student populations. Through multivariate analysis, it is found that students from elite institutions and those with educated parents were more attuned to university rankings in general. However, when testing students' knowledge of rankings, elite university students performed better in knowing their domestic ranking, but worse when guessing their global ranking, while associations to parental education disappeared. This study, the first of its kind in terms of testing student knowledge, illustrates that the impact from university rankings are mitigated by local and individual characteristics.

Purpose: Currently, 1 in 5 college students struggle with suicidal ideation while 7% to 44% engage in nonsuicidal self-injury. Illinois has one of the highest teenage and college student suicide rates in the United States. This pilot study assessed suicide ideation and self-harm behaviors at a public Illinois university. This is the first study to use 5 standardized psychological instruments to investigate these 2 crises in freshmen college students who are all required to reside in dormitories. The main hypothesis was to determine if the independent effects of freshmen students' depression, Five-Factor Model, and Reasons for Living affected the dependent variables, self-harm behaviors and suicide ideation. Methods: Forty first-year college dormitory students completed the Beck Depression Inventory-II, Scale of Suicidal Ideation, Five-Factor Model, Inventory of Statements About Self-Injury, and Reasons for Living Scale in person. Results: Participants were 18 to 19 years old, predominantly female (65%), and non-White (62%). Forty percent reported self-harm behaviors and 19% reported suicidal ideation. The top reasons for contemplated suicide attempts included the inability to solve problems (33%) and attention/revenge (28%). Students experienced high levels of anxiety (55%), self-consciousness (43%), and depression (18%). Depression was associated with suicide ideation (β = 0.05, P =.006), while neuroticism and openness were associated with self-harm behaviors (aOR = 3.36, P =.02, aOR = 0.48, P =.047, respectively). Ninety-five percent reported "responsibility to family" as a Reason for Living. Conclusions: Preliminary evidence necessitates an examination of self-harm and suicide ideation among all freshmen, investigating both risk and protective factors. In the future, a prevention intervention should be implemented campus-wide (and eventually nationwide) for all first-year dormitory students to enhance their mental well-being. [ABSTRACT FROM AUTHOR]