Duke Kunshan University

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality globally. Low-density lipoprotein cholesterol is a causal risk factor for atherosclerotic cardiovascular disease, with multiple classes of cholesterol-lowering therapies effective at reducing atherosclerotic cardiovascular disease risk. Despite robust efficacy data from randomized trials, real-world implementation of guideline-recommended lipid-lowering therapies is suboptimal. Barriers to the implementation of guideline lipid-lowering therapy recommendations exist at the healthcare systems level, the medical therapy level, and the patient level. A combination of strategies, including the incorporation of quality improvement and cost-effectiveness analysis among payers, pharmacist-based educational initiatives, digital health tools directed towards patients, the simplification of drug regimens via polypill, and emerging novel therapies, including PCSK9 gene silencing and editing technologies, may bridge these implementation gaps. This review highlights challenges and solutions to alleviating barriers to optimal implementation of guideline-recommended lipid-lowering therapies.

Maintaining genome integrity in the germline is critical for fertility and organismal survival. Here, we identify C. elegans PARP-2 as an essential and non-redundant regulator of replication-coupled DNA repair. PARP-2 localizes to chromatin during germline development and is also present in the nucleolus; replication stress is associated with changes in its nucleolar distribution, linking fork perturbation to nucleolar signaling and ribosomal homeostasis. Loss of PARP-2 leads to embryonic lethality, larval arrest, and hypersensitivity to replication-blocking and crosslinking agents, accompanied by accumulation of recombination intermediates. Strikingly, a catalytic-dead mutant (E509K) causes even more severe defects than the null allele, including hyperactivation of DNA damage pathways and elevated apoptosis, revealing that PARP-2 enzymatic activity not only executes repair but also restrains excessive stress responses. Chromatin profiling further shows enrichment of PARP-2 at promoter-proximal, fragile loci, suggesting a constitutive surveillance role. Together, these findings establish PARP-2 as a multifunctional genome guardian that integrates catalytic and structural roles to maintain genome stability and nucleolar function, with implications for understanding PARP-associated disease mutations.

Abstract The Southern Annular Mode (SAM) is the dominant mode of atmospheric variability in the Southern Hemisphere extratropics. While its long‐term positive trend is well‐documented, changes in the amplitude of SAM variability remain poorly understood. Based on reanalysis data and surface‐station observations, we demonstrate that the amplitude of SAM variability has substantially increased over the past eight decades, which is associated with more frequent and severe weather extremes. A simple model and idealized climate experiments reveal that this amplification is primarily driven by enhanced stochastic eddy momentum flux, which is linked to a strengthened meridional temperature gradient. State‐of‐the‐art climate model projections indicate that SAM variability will likely continue to intensify throughout the 21st century, driven by a further increase in the meridional temperature gradient. These findings highlight a critical but previously overlooked response of large‐scale circulation to climate change, with important implications for assessing and mitigating future climate risks across the Southern Hemisphere.

Abstract Generative artificial intelligence (GenAI) is rapidly reshaping writing education, yet discussions of AI literacy often foreground tool knowledge and strategic use without adequately theorizing how power operates in AI-mediated literacy practices. This article conceptualizes Critical Artificial Intelligence Literacy (CAIL) in writing education by integrating power dynamics into existing accounts of digital, critical, and AI literacies. Drawing on a qualitative case study of five Chinese English as an Additional Language (EAL) students, the study analyzes screen recordings, written drafts, and semi-structured interviews to examine how students negotiate AI across algorithmic outputs, linguistic expression, cultural reference, and learner agency. Findings show that AI’s authoritative-sounding language and uneven reliability position students as vigilant evaluators who corroborate information, manage citation risk, and recalibrate trust. Students also navigate tensions between AI-driven standardization and personal voice, and between homogenized cultural framings and situated cultural meaning-making. Across these negotiations, writing emerges as a posthuman, distributed activity in which agency is co-produced within human–AI assemblages, making empowerment contingent on learners’ capacity to critically attribute, contest, and strategically incorporate AI contributions. The article argues that CAIL should be conceptualized as the development of AI-related knowledge and strategies together with reflective understanding of the power dynamics shaping AI-mediated writing.

We consider the stationary distribution of the simple random walk on the directed configuration model with bounded degrees. Provided that the minimum out-degree is at least 2, with high probability (whp) there is a unique stationary distribution (uniqueness regime). We show that the minimum positive stationary value is whp n−(1+C+o(1)) for some constant C≥0 determined by the degree distribution, answering a question raised by Bordenave, Caputo and Salez (Probab. Theory Related Fields 170 (2018) 933–960). In particular, C is the competing combination of two factors: (1) the contribution of atypically “thin” in-neighbourhoods, controlled by subcritical branching processes; and (2) the contribution of atypically “light” trajectories, controlled by large deviation rate functions. Additionally, we give estimates for the expected lower tail of the empirical stationary distribution. As a by-product of our proof, we obtain that the hitting and the cover time are both n1+C+o(1) whp. Our results are in sharp contrast to those of Caputo and Quattropani (Probab. Theory Related Fields 178 (2020) 1011–1066) who showed that under the additional condition of minimum in-degree at least 2 (ergodicity regime), stationary values only have logarithmic fluctuations around n−1.

In the United States (US), communities that share the reality of relatively poor health are often on differing sides of a growing political divide. Might community-based participatory research (CBPR) promote inter-community understanding and mutual support? We conducted a scoping review of English-language literature on CBPR in the United States that utilized what we term "purposeful diversity." By purposeful diversity, we mean studies that intentionally involved partnerships with communities of differing race/ethnicity, socioeconomic status, geographic regions, gender/sexual orientation, religions or age in order to achieve a specific result. Only 41 partnerships (described in 65 papers) met our review criteria. Purposeful diversity in ethnicity/race was most common. Community advisory boards, community co-investigators, and community membership on steering committees were prevalent forms of community participation. Frequently, reasons for involving diverse partners were not given; those offered most often were the disproportionate burden of poor health on the communities participating. While many partnerships reported benefits of diversity, the only benefit frequently mentioned was success in recruiting diverse participants. Fewer than 40% of partnerships addressed challenges from working with diverse communities; barriers to communication and understanding were the most common. Fewer than 20% of partnerships reported strategies to address these challenges. Even fewer documented results of such strategies or methods they used to explore the influence of community diversity. Despite the focus of CBPR on structural disadvantage and the possibility of structural change, the potential of this approach for addressing inter-community conflict is virtually unexplored.

Background: The one-year SINEMA trial demonstrated improved blood pressure (BP) control and reduced mortality up to 72 months after the intervention. This article aims to assess between-arm differences in mean annual cumulative BP and to explore whether the associations between cumulative BP and biofunctional outcomes differed by trial arm. Methods: Post-hoc secondary analysis of the SINEMA cluster-randomized trial, which recruited 1299 adults with stroke from 50 rural villages in Hebei, China, between 2017 and 2018. The 12-month intervention was followed by observational assessments at 72 and 84 months post-baseline. BP was measured during each face-to-face follow-up, assessed by blinded assessors at baseline, 12, 72, and 84 months. Mean annual cumulative systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) were calculated. Biofunctional outcomes included health-related quality of life, modified Rankin Scale, activities of daily living, physical function, and cognition function. Results: Among 897 participants (mean age 62.7 years; 40.8% female) with complete data across all assessment, the intervention arm demonstrated significantly lower mean annual cumulative SBP (?2.2 mm Hg; 95% CI, ?3.9 to ?0.6), DBP (?1.6 mm Hg; 95% CI, ?2.4 to ?0.7), and MAP (?1.8 mm Hg; 95% CI, ?2.8 to ?0.8), not PP, compared with usual care. Significant associations between cumulative BP and biofunctional outcomes were observed in the control arm while not in the intervention arm. Interaction effects between trial arm and cumulative BP were significant for multiple outcomes, most prominently for cumulative SBP. Conclusions: The one-year SINEMA intervention was associated with lower cumulative BP burden over 72-84 months but did not improve overall biofunctional outcomes. Secondary analyses revealed that the association between cumulative BP burden and biofunctional decline differed by intervention arm, suggesting cumulative BP exposure may be an important long-term risk indicator and the intervention may modify BP-outcome relationships through mechanisms requiring further investigation.