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Burch Fellowship Video 2025: The intersection of Art and Social Change in Kigali Rwanda
No full textA video reflection of my summer working at Ikirenga Art and Cultural Center and Inema Arts Center funded by the Honors Carolina Burch Fellowship: touching on the work, people, and reflective moments. My summer in Kigali was as beautiful as the art I experienced... thank you for listening.
Safeguarding Merit: Citizen Support for Civil Service Protections Against Political Interference
Full text linkPresident Trump altered the U.S. federal civil service system by reducing merit‐based protections for bureaucratic expertise and expanding the scope of political appointments, shifting the balance long established under the Pendleton Act of 1883. Similar reforms have occurred at the state level with moves to at‐will employment. These shifts raise questions about what shapes public support for merit system protections. Using data from the 2023 Cooperative Election Survey, we examine how public service motivation (PSM), political knowledge, and ideology influence support for political neutrality and protection from political coercion. We find that political knowledge and PSM are positively correlated with favorable perceptions of current merit system protections. Interestingly, there is no significant association between ideology and support for merit protections. These findings suggest that informed and motivated citizens are more likely to support meritocratic principles, highlighting the need for public education on merit systems' role in sustaining democratic governance. Evidence for Practice Public officials and civil service organizations should invest in educational initiatives to both increase political knowledge and inform citizens about the role and benefits of merit‐based hiring and protections in government. The study suggests that political knowledge is positively associated with support for these principles. In 2023, there was no significant association between political ideology and support for merit system protections, including provisions that provide for a politically neutral civil service and protection of government employees from political coercion. Broad public support for merit system protections suggests that public personnel systems with these safeguards align with the democratic preferences and values of the U.S. electorate. Increasing public service motivation among the electorate may also increase support for merit system protections
Distinct PlzC mechanisms integrate chemotaxis and c-di-GMP signaling to regulate Vibrio cholerae motility and biofilm formation
Full text linkSignificance Bacterial motility and biofilm formation critically facilitate adaptation and survival and are regulated by the second messenger c-di-GMP. Vibrio cholerae PilZ domain proteins are c-di-GMP effectors, but the mechanisms by which they govern cellular processes are poorly understood. This study identifies PlzC as a critical integrator of motility and biofilm development via multiple pathways. PlzC promotes motility by regulating CheX, a CheY-3 phosphatase that impacts migration direction. While CheX modulates directional changes through CheY-3 dephosphorylation, PlzC more broadly impacts biofilm maturation, indicating PlzC has a dual regulatory role that targets different stages leading to biofilm formation. PlzC is a key link between chemotaxis and c-di-GMP signaling, providing insight into bacterial adaptability and potentially serving as a target for therapeutic approaches.Bacterial motility and biofilm formation are essential for the adaptation and survival of Vibrio cholerae, the causative agent of cholera. In many bacterial species, the second messenger c-di-GMP regulates these processes through PilZ domain proteins, however the downstream mechanisms have remained poorly defined. Here, we identify the PilZ domain protein PlzC as a key positive regulator of motility and biofilm formation through distinct mechanisms. A suppressor screen for mutants restoring ΔplzC migration identified downstream regulators, including CheX, a CheY-3 phosphatase. Genetic and phenotypic analyses revealed that PlzC promotes motility by modulating CheX, thereby influencing the frequency of direction changes during swimming. Notably, the role of PlzC in motility regulation is independent of CheZ, another CheY-3 phosphatase, demonstrating that among the two CheY-3 phosphatases, only CheX is under PlzC control. This distinction suggests that CheY-3-P levels are regulated by at least two separate signaling pathways, one of which operates through PlzC. Despite its function in motility, CheX is not required for PlzC-mediated biofilm regulation, indicating pathway specificity. PlzC regulates biofilm formation through a mechanism that involves c-di-GMP binding, separating it from its CheX-dependent motility regulation. Together, our findings establish PlzC as a central regulator linking CheX-mediated motility and c-di-GMP signaling, thereby impacting motility and biofilm formation in V. cholerae
Enlarged Perivascular Spaces Among Hispanic and Latino Adults in SOL-INCA-MRI.
Full text linkBACKGROUND: To examine preliminary associations between enlarged perivascular spaces (ePVS) and cerebrovascular small-vessel disease, cortical atrophy, and cognitive impairment among a select cohort of Hispanic and Latino adults. The Hispanic and Latino population has a higher prevalence of dementia and vascular disease but is underrepresented in dementia research. This study addresses this gap by investigating ePVS in a large convenience cohort of Hispanic and Latino individuals. METHODS: Brain magnetic resonance images from a convenience sample of 2161 participants, including 28.8% of individuals aged >50 years with cognitive impairment from the SOL-INCA-MRI (Study of Latinos-Investigation of Neurocognitive Aging Magnetic Resonance Imaging) study were analyzed. ePVS volume in the cerebral white matter was quantified using an automated method and then residualized with total cerebral volume. Associations between residualized mean ePVS volumes and demographic factors, magnetic resonance imaging measures, and cognitive impairment were assessed using regression models. RESULTS: Residualized mean ePVS volume was significantly associated with age (P<0.001) and varied significantly by Hispanic and Latino heritage. After adjusting for age, sex, education, and heritage, ePVS volume was associated with infarction on magnetic resonance imaging (P=0.03), white matter hyperintensity volume (P<0.001), presence of cerebral microbleeds (P=0.009), cortical gray matter (P<0.001), and hippocampal (P<0.001) atrophy. Participants who are cognitively impaired also had significantly larger ePVS volumes (P=0.004). No significant sex differences in ePVS volume were observed when adjusting for head size. CONCLUSIONS: This convenience sample of Hispanic and Latino individuals demonstrates significant associations between ePVS volume and established markers of cerebrovascular small-vessel disease, cortical atrophy, and cognitive impairment. These findings suggest that ePVS may be useful as an additional marker of vascular brain injury within this cohort
Are There Causal Associations Between Obsessive‐Compulsive Disorder and Cardiometabolic Phenotypes? A Genetic Correlation and Bi‐Directional Mendelian Randomization Study
Full text linkIn epidemiological studies, obsessive-compulsive disorder (OCD) is robustly associated with increased risk of cardiometabolic disorders, including cardiovascular diseases, type 2 diabetes, and obesity. However, the mechanisms behind these associations are unclear. We conducted genetic correlation analyses to explore shared genetic etiology and bi-directional summary-level Mendelian randomization (MR) to explore potential causal effects between genetic liability to OCD and 14 cardiometabolic phenotypes (e.g., coronary artery disease, blood pressure, body mass index [BMI]). If causal effects were observed, we planned to conduct multivariable MR to explore indirect effects via health behaviors. We found no evidence for genetic correlations between OCD and any of the cardiometabolic phenotypes under study, except for a negative correlation with BMI (rG = -0.123, SE = 0.029, p < 0.001). Summary-level MR showed no evidence for causal effects. Therefore, multivariable MR was not conducted. We found limited evidence for shared genetic etiology or causal effects using the largest OCD GWAS to date. However, we were predominantly only powered to detect medium to large effects in the direction of OCD to cardiometabolic traits, leaving the possibility of smaller causal effects existing. Future studies with larger, more representative samples will help to further interpret findings
Accelerating Novel Therapies for Sickle Cell Disease with RWE: ASH RC Data Hub as a Strategically Coordinated Registry Network
Full text linkReal-world evidence (RWE) has been used to improve quality of care, accelerate innovation, and evaluate emerging therapies for drugs, devices, and biologics. The Coordinated Registry Network (CRN), aggregating and linking highly curated patient data, has emerged as a model for RWE generation that has guided the development of the ASH Research Collaborative® (ASH RC) Data Hub. With the aim of bolstering research, enhancing clinical care, and expediting evidence generation using RWE, ASH RC, and the Innovative Genomics Institute (IGI) launched a joint initiative, "Accelerating Innovations for Sickle Cell Disease (SCD) with Real-World Evidence," to evaluate and make recommendations to the Data Hub. An expert panel used a "maturity model" to evaluate: 1) Data Hub standardization of RWE guidelines to ensure successful monitoring of new therapies' safety and effectiveness; and 2) the Data Hub's engagement with patients (including collection of data on patient experience) and collaboration among partners, including regulators, industry, and clinicians. The Data Hub gathers patient-level data from electronic health records, with plans to incorporate data from individuals receiving gene therapy. The program is currently curating and aggregating data on approximately 27,000 individuals with SCD cared for across 22 hospitals in the United States. The SCD Data Hub Program includes a total of 56 centers, some of which are not yet contributing data, which will increase the total cohort to approximately 50,000 patients. The unique organizational structure of the CRN model facilitates acceleration of innovation through collaborative relationships between multiple clinical sites and partners with various evidentiary needs
Role of real-world evidence from patient registries for psoriasis in decision-making: a systematic review
Full text linkINTRODUCTION: Treatment of moderate to severe psoriasis typically requires the use of multiple systemic therapies over a patient's lifetime. The efficacy and safety of systemic treatments are typically evaluated in clinical trials; however, patient registries are increasingly used to monitor long-term outcomes of systemic therapies for psoriasis in real-world settings. Psoriasis registries also generate important real-world evidence about psoriasis treatment that may facilitate a greater understanding of outcomes outside of a controlled clinical trial setting. This study thus characterises the design and measures used in real-world studies of psoriasis treatment from patient registries and assesses its use in informing clinical guidelines and reimbursement decisions. METHODS AND ANALYSIS: A systematic literature review was conducted to identify real-world observational studies that used psoriasis registry data. PubMed and Embase were searched for English-language studies published between January 2018 and January 2023. To assess how real-world studies, clinical guidelines, and reimbursement and coverage reports have informed practice, treatment, and reimbursement guidelines, a narrative review of recommendations was conducted. All results were screened by two independent reviewers (LP and TAS) using prespecified inclusion and exclusion criteria. Outcomes of interest were extracted into Excel, with all conflicts resolved through discussion/consensus. Tables displayed outcomes and research topics first by year, then by registry. PROSPERO REGISTRATION NUMBER: CRD42023402431
International Comparison of Benzodiazepine Prescription for Older Adults in Acute Care Hospitals
Full text linkDear Editor,
Benzodiazepines (BZD) are harmful to older adults. They are associated with increased mortality, and increased hospitalization-associated complications (HAC), such as delirium and falls. Despite these known adverse events, BZD use remains prevalent in older adults and represents a potentially modifiable risk factor for adverse outcomes. Although acute care hospitals are at particularly high risk for HAC from BZD usage, there has been little systematic research into the prescribing practices of BZD. The purpose of this study was to investigate the current status of BZD prescriptions, including Z-drugs (ZD), in acute care hospitals in the United States and Japan, where guidelines recommend reducing and discontinuing BZD, and to conduct an international comparison
Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.
Full text linkObesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05-1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (ORper SD = 1.12, 95% CI: 1.02-1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL
Millimetre‐Scale Stratification of Microbial Communities in Hydrothermal Sediments
Full text linkResolving the spatial organisation of microbial populations in environments shaped by steep thermal and geochemical gradients remains a challenge in environmental biogeochemistry. Conventional molecular biomarker or gene‐based approaches typically require large volumes of homogenised samples, limiting their ability to depict spatially structured microbial ecosystems, where critical microbial processes occur on millimetre scales. To overcome these limitations, we applied high‐resolution mass spectrometry imaging (MSI) to an 11.5 cm long sediment section from the hydrothermal Cathedral Hill mat complex in the Guaymas Basin, known for its extreme temperatures and sharp geochemical gradients. The μm‐scaled spatial resolution unveiled a nuanced lipidome zonation tightly compressed to a narrow 5‐cm segment below the sediment–water interface. The surface layer (above 1.1 cmbsf) hosts molecular patterns primarily shaped by opposing oxygen and sulphide gradients, followed by a near‐seamless transition to an anoxic zone dominated by anaerobic methane‐oxidising archaea (ANME) and sulphate‐reducing bacteria (SRB). At greater depth, molecular signals indicative of active microbial communities remained below the detection limit except for diverse, potentially ANME‐ and SRB‐related lipids concentrated within a siliceous concretion. The sharp transitions in lipid zonation hint at persistent redox zones and resilient microbial niches under intense fluid flow and dynamic geochemical gradients