University of North Carolina System

Human activities have increased atmospheric reactive nitrogen (N) deposition, with important consequences for ecosystem biogeochemical cycles. In forest ecosystems, tree canopies act as active filters that intercept, transform and redistribute atmospheric N before it reaches to the soil. These canopy-level processes determine the chemical forms of N that become available for biological uptake or are transferred to the soil. Despite their importance, the temporal variability of these processes remains poorly understood, particularly in Mediterranean ecosystems with pronounced seasonal contrasts.In this study, we investigated the seasonal dynamics of atmospheric N transformations within the canopy of a Mediterranean Holm oak forest (Quercus ilex / Q. rotundifolia) in Spain. We focused on canopy-scale nitrification processes and the abundance of N-fixing and nitrifying microorganisms associated with the phyllosphere and precipitation. Canopy N fluxes were quantified, nitrate sources were identified using Δ¹⁷O isotopic signatures, and microbial abundances were quantified by qPCR, to explore seasonal dynamics and their environmental drivers.Our results show that the canopy acted as a net sink for atmospheric N throughout the year, indicating that N inputs did not exceed ecosystem demand and suggesting potential N limitation. The nitrate measured in throughfall samples indicated a predominantly atmospheric origin during most of the year (76–92%). In contrast, during summer up to 76% of the nitrate was derived from in situ biological processes at canopy level. These enhanced biological transformations were correlated with weather conditions, particularly the higher temperatures and dry conditions typical of summer, which may favour nitrification and promote the accumulation of N compounds on leaf surfaces. Reduced plant activity and lower N uptake during summer further prolong N residence time within the canopy, increasing the likelihood of microbial transformations. Both archaeal and bacterial nitrifiers, as well as N-fixing microorganisms, were detected year-round in the phyllosphere and precipitation. Archaeal nitrifiers consistently outnumbered bacterial ones, and showed a marked increase during summer, driven by higher radiation, temperature and lower humidity. This pattern suggests that archaea may play a significant important role in nitrification, coinciding with the highest nitrification rates observed in summer. These findings highlight the crucial function of canopy processes in regulating N fluxes in Mediterranean forests, particularly during summer. The seasonal dynamics of biological transformations and microbial communities emphasise the influence of environmental conditions on N cycling.

The chromatin is folded into three-dimensional (3D) structures, and aberrant 3D chromatin folding has been implicated in cancer. We performed ATAC-seq and TOP2A ChIP-seq to assess the potential effects of various anthracycline drugs on the chromatin architecture. We found that specific anthracycline variants selectively disrupt chromatin looping anchors by interfering with CTCF binding, suggesting an additional therapeutic mechanism of anthracycline drugs targeting the 3D genome. Hi-C experiments in K562 cells treated with anthracycline drugs revealed widespread disruption of 3D chromatin organization, including altered long-range regulation at the Myc locus. Furthermore, AML patients treated with anthracycline drugs exhibited changes in chromatin structures near possible looping anchors, which were associated with distinct clinical outcomes. Together, our findings indicate that anthracycline drugs function as potent and selective epigenomic modulators, with the capacity to further target the 3D genome to exert anticancer effects, highlighting their potential for personalized therapy in tumors with aberrant 3D chromatin architecture.

ABSTRACT.The coronavirus disease 2019 pandemic showcased the power of genomic surveillance in tracking infectious diseases, driving rapid public health responses, and global collaboration. This same infrastructure is being leveraged for malaria molecular surveillance (MMS) in Africa to address challenges such as artemisinin partial resistance and deletions in the Plasmodium falciparum histidine-rich protein 2 and 3 genes. However, variability in reporting sequencing methods and data reporting currently limits the validation, comparability, and reuse of data. To maximize the impact of MMS, minimal and optimal data that are key for validation and maximizing transparency and findable, accessible, interoperable, and reusable principles are proposed for reporting. Rather than focusing on specific data formats, in the current study, the authors propose what should be reported and why. Progressing to reporting individual infection-level polymorphism or microhaplotype data is central to maximizing the impact of MMS. Reporting must adhere to local regulatory practices and ensure proper data oversight and management, preventing data colonialism and preserving opportunities for data generators. With malaria’s challenges transcending borders, reporting and adopting standardized practices are essential to advancing research and strengthening global public health efforts.

ObjectiveGlycemic control in hospitalized patients with diabetes is crucial yet remains challenging. Hypoglycemia poses an increased risk of complications, prolonged stays, and mortality. Strategies such as basal-bolus-correction insulin can help balance glycemic control and reduce hypoglycemic events. This study evaluated the impact of a mandatory electronic medical record–based insulin order set across a multihospital system.MethodsThis quality improvement project was implemented at 10 hospitals in North Carolina, including urban, rural, and community sites. The intervention introduced a standardized insulin order set with multiple fail-safes addressing insulin-to-nutrition mismatch, basal and bolus coverage, and dose accuracy. The primary outcome was hypoglycemia days per 1000 patient-days in nonpregnant adults. Secondary outcomes included hyperglycemia days and the rate of hemoglobin A1c orders.ResultsHypoglycemia days across all sites decreased from 13 to 10 per 1000 patient-days (24% reduction, P < .01), with 9 sites showing declines (7%-39%) and 1 site showing an increase. Hyperglycemia days decreased from 90 to 76 per 1000 patient-days (16% reduction, P < .01). Hemoglobin A1c ordering improved from 60% to 67% (12% increase, P < .01). The implementation of a system-wide electronic medical record–based insulin order set reduced hypoglycemia rates across 9 of 10 hospitals without adversely affecting hyperglycemia. The standardized protocol contributed to these improvements. Site-specific variations in outcomes suggest the need for tailored interventions in certain locations.ConclusionImplementation of a mandatory, standardized insulin order set with multiple fail-safes across a multihospital system effectively reduced hypoglycemic events, thus demonstrating their value in managing inpatient diabetes.

Abstract We demonstrate that unexpected increases in enforcement have a temporary but costly impact on labor supply among noncitizen farmworkers. Analyzing Current Population Survey data and immigration‐related arrests, we find that unexpected increases in immigration arrests decrease labor force participation (LFP) among noncitizen farmworkers by up to 3.4 percentage points and reduce weekly work hours by up to 23.1% per month. These effects translate into a 1.38 percentage point decline in LFP and a 9.08% reduction in weekly hours worked across farmworkers. Our results suggest that localized enforcement exerts downward pressure on immigrant populations during periods when policies are not activated.

Preceptors are critical in training learners and supporting learner professional identity formation (PIF). This manuscript describes pharmacist preceptors' professional identities (PI), pivotal moments and influences that shaped those PIs, and how this impacts their precepting to inform future preceptor development. Semi-structured interviews with experienced preceptors from five experiential education programs were transcribed and analyzed. An abductive approach was used for coding, followed by thematic analysis. Twenty-two participants from various settings described their PI as a medication specialist, care provider, safeguard, educator, and/or manager. Six themes were recognized across the interview question data as critical to forming professional identity. These included: common elements among pharmacists' PIs such as being a medication-related problem solver (theme 1) and helping/serving others (theme 2); a connection between preceptor identity and participant precepting practices (theme 3); and the importance of role models (theme 4), practicing autonomy (theme 5) and being treated as a pharmacist (theme 6) in developing the participants' PI. These findings suggest that preceptor development could focus on introducing the concept of PIF, build an understanding of the importance of role models and pivotal moments in supporting PIF, and support the development of preceptor identity as a clinician, educator, or teacher. Critically, the findings from this analysis suggest that a preceptor's PI can influence how they precept, the types of experiences they facilitate for learners, and the norms and values they model. These findings will inform future preceptor development programs about their learner's PIF.