Citations

Toxins from ingested water can significantly affect overall physical health in children and adults. In the United States, domestic water wells are not commonly tested for any heavy metal contaminants. It is well-known that chronic arsenic ingestion from water is linked to serious health effects. We surveyed patients at our academic institution via emailed questionnaires in 2023 to determine whether those with children living at home reported different patterns of behavior around well water testing as compared to those without. Survey data were collected from 8994 respondents in the U.S. Midwest who reported using residential well water. Results were used to evaluate the influence of children in the home on testing behaviors, and secondarily, whether parental demographics affected testing frequency. Respondents with children at home did not report increased testing frequency compared to those without. In parents who did report testing, having more children, being younger, and living in Wisconsin were associated with an increased frequency. Parental gender, race, and ethnicity did not correlate with testing behaviors. A total of 70% of respondents did not feel concerned about their water safety and 85% were not concerned about arsenic specifically in their water. Increased risk of toxicity to children from arsenic does not appear to influence reported well water testing behavior among parents.

Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is due to a defect in metabolism of long-chain fatty acids. Infants with VLCADD may experience cardiomyopathy, hypoglycemia, or even death; thus, early detection and intervention is crucial. The spectrum of disease and natural variation in newborn metabolism, however, lead to overlap in acylcarnitine values between affected and unaffected individuals, which contributes to the difficulty in identifying true positive cases while minimizing false positive cases. VLCADD was added to the state of Wisconsin’s newborn screening (NBS) panel in 2000. A previous retrospective review of VLCADD screen positive cases identified between 2000 and 2014 resulted in a change to the screening algorithm. Following implementation, a reduction in the percentage of false positive screens from 25.3% to 20.4% was observed between 2015 and 2021. The overall PPV also decreased, from 37.2% to 28%, due to an increase in the number of carriers identified (27.5% of cases in 2000–2014 and 51.8% of cases in 2015–2021). A data review also identified three long-chain acylcarnitine elevations (C14:1, C14:1/C16, and C14:1/C2) that had statistically significant differences in concentrations in true positive populations versus false positive populations. Utilization of the C14:1, C14:1/C16, and C14:1/C2 values in newborn screening may provide clearer distinction between true positive and carrier populations and additionally increase the PPV of this screen.

Objective The objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis. Methods The Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation. Results We present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response. Conclusion This guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

Objectives/Goals: This project will enrich our understanding of basal breast carcinogenesis, highlighting the distinct biological differences in breast cancer risk between non-Hispanic Black (NHB) or non-Hispanic White (NHW) women, but also has the potential to provide real-world solutions thereby contributing to reducing health disparities in breast cancer outcomes Methods/Study Population: In the biological investigation, I am utilizing a unique cohort of normal breast tissues from Mayo Clinic patients who underwent breast reduction surgery that have self-identified as NHB or NHW premenopausal women. From these tissues, we are able to subculture human mammary epithelial cells, which we will use for our consequent experiments. For the qualitative study, I aim to recruit up to 40–50 eligible NHB women identified at increased risk for breast cancer and conduct semi-structured qualitative interviews informed by the National Institute on Minority Health and Health Disparities Research Framework. Results/Anticipated Results: Gene expression profiling on our cohort of 15 NHB and 40 NHW premenopausal women identified a gene expression signature in NHB women indicative of elevated Hedgehog signaling, a key factor in triple-negative breast cancer (TNBC) development and progression. I hypothesize that persistent activation of Hedgehog signaling within NHB women instigates the proliferation and transformation of basal stem cells within the breast, thus fueling TNBC development. Understanding the perceptions and experiences of NHB women that are identified as being at an increased risk for BC will aid in the identification of barriers and facilitators to their risk reduction care and in turn provide implementation strategies that could contribute to alleviating the racial disparity seen in TNBC morbidity, mortality, and preventative care. Discussion/Significance of Impact: The significance of this project lies in its dual approach, uncovering basal breast cancer mechanisms in a high-risk group using normal breast tissue and evaluating the perspectives from NHB women to enhance the practical relevance of our findings.

Background and Aims: Screening for diseases can have psychological impacts, such as anxiety, and requires acceptability from the population to be effective. This study examined the perspectives on the benefits and harms of screening for metabolic dysfunction–associated steatotic liver disease (MASLD) among the general population to optimize screening practices. Approach and Results: A survey was sent to participants enrolled between 2020 and 2024 in a prospective MASLD screening study in Olmsted County, MN. The survey assessed participants' perceived anxiety, stigma, quality of life, preferred screening methods, financial concerns, and lifestyle impacts following screening and diagnosis. Of the 461 participants, 342 (74%) completed the survey. Overall, 14% of participants reported screening-related anxiety, and 14% were concerned about disclosing a potential MASLD diagnosis to others. Among those without a MASLD diagnosis, 99% felt reassured about their liver health, 48% reported an improved quality of life, and 25% made lifestyle changes pertaining to their diet, alcohol use, and physical activity. Of the 77 participants diagnosed with MASLD, 52% experienced some anxiety about their new diagnosis; however, 95% and 97% considered it important to receive an early MASLD diagnosis to mitigate the risk for cirrhosis and cardiovascular disease, respectively. Notably, 79% of diagnosed participants found the diagnosis beneficial in adopting healthier habits, with 30% achieving a >10% weight loss after screening. Conclusion: This population-based survey demonstrates that the perceived benefits of proactive MASLD screening, such as increased awareness, lifestyle changes, and early diagnosis, outweigh the harms. These findings highlight the importance of early screening through patient-centered protocols to improve health outcomes.

Abstract Multiple myeloma (MM) is a complex hematological malignancy characterized by genomic changes and transcriptomic dysregulation. Initial exome sequencing approaches have failed to identify any single, frequent (>25%) mutation in the coding genome. However, using whole-genome sequencing, we found that one of the genomic regions most frequently mutated (62% of the patients with MM) was the 5′ untranslated region and/or intron 1 of the BCL7A gene. RNA-sequencing data from a large cohort suggest a loss of BCL7A expression in a large majority of patients with MM as compared with normal plasma cells. BCL7A loss of function in a panel of MM cell lines led to a highly proliferative phenotype in vitro and in vivo, whereas its ectopic expression significantly reduced cell viability, suggesting a tumor suppressor function for BCL7A in MM. We studied the cellular and molecular effects of BCL7A loss and observed that it endows myeloma cells with proliferative potential in cooperation with the plasma cell–defining transcription factor IRF4. BCL7A is involved in a direct protein-protein interaction with IRF4, limiting its DNA-binding activity. Loss of BCL7A thus enhances the expression of IRF4-associated cytokines and reduces mitochondrial metabolism and reactive oxygen species levels. Our study therefore suggests that BCL7A loss provides the necessary molecular change to allow IRF4-mediated transcriptional activity and MM cell growth and survival.

ABSTRACTObjectiveThis scoping review explores the multifaceted experience of cancer survivorship in Sub‐Saharan Africa (SSA), with a focus on the post‐treatment phase. The primary objective is to examine the psychosocial, cultural, and economic factors that influence post‐treatment survivorship care and outcomes.MethodsA comprehensive literature review was conducted using databases such as Web of Science Core Collection to identify studies published between 2000 and 2023. Eligible studies focused on post‐treatment cancer survivorship in SSA. Data were extracted, analyzed, and synthesized to identify key themes and research gaps.ResultsThe review identified substantial psychological distress among survivors, including depression, anxiety, and insomnia, often exacerbated by financial toxicity and limited access to psychosocial support services. Cultural factors, such as spiritual beliefs, reliance on traditional healers, and cancer‐related stigma, influenced healthcare‐seeking behaviors and overall well‐being. Despite these challenges, social support networks, religiosity, and targeted psychosocial interventions improved emotional resilience and quality of life. However, major gaps remain, including insufficient integration of cultural beliefs into survivorship care, inadequate long‐term follow‐up (LTFU) programs, limited oncofertility support, and a lack of regionally diverse and longitudinal data.ConclusionsCancer survivorship in SSA is shaped by intricate psychosocial, cultural, and economic dynamics that extend beyond clinical care. Addressing these challenges requires culturally sensitive, evidence‐based interventions, including financial counseling, spiritual care integration, and the establishment of structured LTFU programs. Additionally, expanding access to oncofertility support and integrating culturally relevant psychosocial services can further enhance survivorship outcomes. Strengthening collaboration between policymakers, healthcare providers, and researchers—through interdisciplinary task forces, psycho‐oncology workforce development, and community‐driven initiatives—is essential for improving post‐treatment outcomes and advancing cancer survivorship care in SSA.

AbstractBackgroundTransgender and gender‐diverse (TGD) patients experience challenges and disparities when seeking health care across a multitude of settings. Studies have demonstrated that TGD individuals experience bias when interacting with health care providers, including pharmacists in the community and hospital settings. Without proper training, pharmacists are less likely to be prepared to provide equitable and optimal patient care to TGD patients. This quality improvement initiative aimed to identify gaps in pharmacist knowledge and comfort with regard to TGD health care.MethodsA 29‐item reflective questionnaire was designed to collect information on pharmacist training and experiences in caring for TGD patients. The survey was distributed via email to all 490 pharmacists within a single health system and responses were collected from October 23, 2023 to November 3, 2023.ResultsA total of 116 pharmacists completed the survey, for a response rate of 24%. Although 77% of respondents reported caring for a TGD patient, only 21% reported receiving any formal education or training on TGD health care. While 83% of respondents agreed that formal education on TGD health care is important, and 90% indicated that education on gender‐affirming therapy is important, a majority of pharmacists disagreed that they were comfortable with making recommendations and providing counseling on gender‐affirming therapy. A majority of pharmacists were interested in formal education and engaging in departmental initiatives to improve TGD care.ConclusionsThere was a gap in confidence and education in caring for TGD patients among pharmacists practicing in a single academic institution. Pharmacists reported that more education is warranted to bridge current gaps in pharmacist comfort and TGD health care.