Citations

Background: The external environment continuously shapes human perception, often without conscious awareness. This influence can be objectively studied using non-invasive recordings of brain activity in controlled virtual reality (VR) settings. We hypothesized that brief presentations of natural features would elicit distinct neural oscillatory patterns detectable through changes in the spectral power of resting-state electroencephalogram (EEG) activity in specific brain regions. Methods: To test this, participants passively viewed three minimalist VR environments—with and without biophilic elements—while their EEG was recorded. Results: Our results revealed consistent changes in spectral power, particularly suppression in the alpha band and an increase in the theta band in the occipital cortex. Conclusions: These findings support the use of resting-state EEGs in immersive VR as a promising and objective method for evaluating how specific design elements influence neural activity, offering valuable insights into the field of neuro-architecture.

Abstract eSource – particularly EHR-to-EDC – is an emerging paradigm in clinical research that enables automated transfer of electronic health record (EHR) data into electronic data capture (EDC) systems, with the potential to reduce site burden, improve data quality and accelerate oncology clinical trial workflows. However, widespread implementation remains limited due to technical, regulatory and operational barriers. To address these challenges, the European Institute for Innovation through Health Data (i~HD) launched the eSource Scale-Up Task Force in 2024. This multi-stakeholder initiative brings together leading oncology centres and pharmaceutical sponsors to establish a consensus-driven roadmap for eSource adoption. Central to this effort are three foundational resources: readiness criteria for early adopters, a performance indicator framework for monitoring success and an operational playbook to guide implementation. This article provides a structured overview of the Task Force’s objectives, collaborative model and outputs, with specific attention to its focus on interoperability, regulatory alignment and real-world validation. While initially developed for oncology, the Task Force’s framework is applicable across therapeutic areas characterized by data-intensive workflows.

Objectives: Participant retention is essential in prospective studies to minimize bias and maintain validity. This study aimed to estimate retention rates and identify factors influencing attrition in a multicenter cohort (PROCEED) of US adults with acute/recurrent acute pancreatitis (AP/RAP) and chronic pancreatitis (CP). Methods: Participants from the PROCEED study with AP/RAP or CP eligible for follow-up within the designated visit window were included. Retention was defined as completing at least one follow-up visit during the observation period. Retention was analyzed by follow-up mode (in-person and/or medical record review) and disease type (AP/RAP and CP). Retention factors were assessed using univariate analyses (Wilcoxon rank-sum for continuous variables, χ 2 /Fisher's exact for categorical) and multivariable logistic regression. Missing data were adjusted using multiple imputations in statistical modeling. Results: Among 1279 participants (AP/RAP: n=632, median age 47, 48.9% female; CP: n=647, median age 54, 46.5% female), we observed high cumulative and annualized retention rates, with improved retention when incorporating medical record reviews. In multivariable regression analyses, older age was statistically significantly associated with in-person retention in the AP/RAP group ( P =0.0001), while a higher self-reported physical health (assessed with PROMIS Global Health Physical Health T-score) was a key predictor of retention in CP ( P =0.034). Conclusions: Integrating medical records review substantially enhanced retention rates, enabling robust analyses of pancreatitis outcomes and disease progression. Older age and better self-reported physical health were key predictors of retention, highlighting the need for targeted strategies to enhance engagement among younger participants and those with poorer health in long-term studies.

ABSTRACT Aldose reductase inhibitors (ARI) have been identified as a potential treatment for phosphomannomutase‐2 congenital disorder of glycosylation (PMM2‐CDG), a serious condition for which no treatments are approved. We treated a single patient for 36 months 30 months of age at enrollment, under a single‐patient investigational new drug expanded access request, with govorestat (AT‐007), a novel, highly selective, once daily, brain penetrant ARI at a starting dose of 1 mg/kg oral suspension, which was escalated to 30 mg/kg. The primary endpoint was safety. Secondary assessments included liver transaminases, factor XI, antithrombin III, and whole blood and urine sorbitol. Clinical outcomes were also assessed, including Nijmegen Pediatric CDG Rating Scale (NPCRS), Bayley Scales of Infant Development, and Vineland Adaptive Behavioral Scale. Govorestat was well tolerated; no adverse effects were noted. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels improved from a pre‐treatment 12‐month average of 205 and 268 U/L to 63 and 68 U/L, respectively, averaged over 36 months of govorestat treatment at 30 mg/kg. Antithrombin III and factor XI fluctuated with illness throughout the study period but overall increased by 60%–100%, approaching the normal range (> 83% activity) at the 5 mg/kg dose. Whole blood sorbitol decreased in a dose‐dependent fashion, normalizing at the 30 mg/kg dose. The NPCRS improved by 9 points (46%) over the course of treatment. In conclusion, our patient tolerated govorestat without safety concerns. Improvements in liver transaminases, clotting factors, and whole blood sorbitol were observed along with improvements in clinical measures. These findings support further study of govorestat as a potential treatment for PMM2‐CDG.

BACKGROUND The use of Mohs micrographic surgery as a treatment for melanoma is rising, but the reliability of Mohs surgeons in assessing MART-1 melanoma en-face margins has not been evaluated. OBJECTIVE To evaluate interrater and intrarater reliability of Mohs surgeons in interpreting margins of early-stage melanoma. METHODS Twenty Mohs surgeons were asked to independently review images of frozen section MART-1 en-face peripheral margins of in situ or early-stage melanoma. Surgeons determined margins as positive or negative at initial evaluation and 6 weeks later. Primary outcomes were interrater and intrarater reliability. RESULTS Interrater agreement was 84.1% (95% confidence interval [CI]: 75.5%–92.8%) for assessment 1 and 87.5% (95% CI: 78.4%–96.4%) for assessment 2, with kappa values 0.68 (95% CI: 0.50–0.82) and 0.75 (95% CI: 0.57–0.88). Average intrarater percent agreement was 95.0% (95% CI: 70.6%–100.0%) with average kappa 0.90 (95% CI: 0.50–1.00). CONCLUSION Substantial interrater and nearly perfect intrarater agreement was identified among surgeons assessing melanoma margins utilizing MART-1 immunostaining, demonstrating consistent and reproducible assessment of melanoma margins during Mohs cases.

OBJECTIVE To evaluate the impact of community paramedic (CP)-delivered, in-home diabetes self-management education and support (DSMES) for adults with poorly managed diabetes. RESEARCH DESIGN AND METHODS In a pragmatic, single-arm pilot trial, adults with HbA1c ≥9% and a recent emergency department or hospital visit received a 1-month CP-led DSMES intervention. Outcomes included HbA1c, health care engagement, and patient-reported satisfaction. RESULTS Seventy participants (median age 61 years, 50% rural, 84% with type 2 diabetes) completed the intervention. HbA1c declined from 9.8% to 8.2% at 4 months (P < 0.001). Engagement with primary care, endocrinology, and DSMES improved. Satisfaction was high (mean rating 9 out of 10). CONCLUSIONS CP-led DSMES improved glycemic management and care engagement in underserved populations. This scalable model warrants further study.

Purpose of review Sulfate is essential for the sulfation of proteoglycans to maintain cell function. The mechanisms regulating the ‘ins and outs’ of systemic sulfate balance remain incompletely understood. SLC26A1 is an anion exchanger expressed in the kidney. It has recently been identified as a key regulator of plasma sulfate homeostasis in humans. This review summarizes current insights into SLC26A1 function and its role in human diseases. Recent findings Slc26a1-knockout mouse models exhibit reduced plasma sulfate and abnormal sulfate and oxalate homeostasis, accompanied by augmented susceptibility to acetaminophen-induced liver injury and kidney stone disease, although findings on oxalate homeostasis are inconsistent. In humans, rare and common SLC26A1 variants are associated with hyposulfatemia, musculoskeletal abnormalities, and, in some cases, nephrolithiasis. Functional assays confirm disrupted sulfate and oxalate transport of damaging variants. However, the knockout mouse models have been incompletely characterized, and few patients with damaging SLC26A1 variants have been characterized regarding sulfate and oxalate homeostasis and associated diseases. Summary SLC26A1 emerges as a key regulator of sulfate homeostasis, with potential roles in hepatic detoxification, skeletal integrity, and kidney stone disease. Additional mouse models with tissue-specific gene deletion are needed to delineate the role of SLC26A1 in sulfate and oxalate homeostasis as well as disease pathogenesis. Identification of additional patients with damaging variants in SLC26A1 as well as larger population studies may help to elucidate causal relationships of SLC26A1 activity with clinical outcomes.

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.

Abstract BACKGROUND Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome characterized by development of multiple neoplasms, including central nervous system (CNS) hemangioblastomas, renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNETs), and retinal hemangioblastomas. Belzutifan, a hypoxia-inducible factor 2-alpha (HIF-2α) inhibitor, has demonstrated efficacy in treating VHL-associated tumors. This study evaluates our institutional experience with belzutifan in patients with VHL-related tumors. MATERIAL AND METHODS We conducted a retrospective cohort study across three Mayo Clinic sites, including patients aged ≥18 years with genetically confirmed VHL disease who received belzutifan between October 2021 and March 2025. Clinical/radiological data, and adverse events (AEs) were extracted from electronic health records. Tumor responses were assessed using RECIST v1.1 criteria for RCC, pNET, CNS hemangioblastoma. Retinal hemangioblastoma responses were evaluated through ophthalmologic assessments. RESULTS Forty-five patients were included (median age 44 58% female). Sixty-seven percent had RCC, 91% had CNS hemangioblastomas, 53% had pNETs, and 62% had retinal hemangioblastomas. The median duration of belzutifan therapy was 22.6 months (range 1.0-41.4 months). Among patients with RCC (n=26), overall response rate (ORR) was 19% and median time to best response (MTBR) was 7.4 months. Five patients had partial response (PR), 15 had stable disease (SD), and 1 had progressive disease (PD). For CNS hemangioblastomas (n=41), ORR was 12%, MTBR was 6.2 months. 5 patients had PR, 30 had SD, and none had PD. For pNET (n=17), ORR was 41%, MTBR was 8.2 months. One patient had CR, 6 patients had PR, 6 had SD, none had PD. For retinal hemangioblastomas (n=28), 6 (21%) showed improvement, 9 (32%) remained stable, and 3 (11%) showed progression. MTBR was 6.7 months. Treatment-related AEs occurred in 98% of patients. Common AEs included anemia (89%), fatigue (80%), hypoxia (18%), and headache (13%). Grade 3 AEs were observed in 20% of patients, including anemia (7%), hypoxia (9%), fatigue (4%), pneumonitis (2%), loss of consciousness (2%). One patient experienced a grade 4 event (status epilepticus). Anemia management involved iron supplementation (n=11), RBC transfusion (n=3), dose reduction (n=2), treatment holiday (n=8), permanent discontinuation (n=1). Hypoxia management included dose reduction (n=1), treatment holiday (n=3), discontinuation (n=1). CONCLUSION Belzutifan shows clinical activity across various VHL-associated neoplasms in real-world practice, with a manageable safety profile. The lower ORR compared to the phase III trial may reflect differences in baseline disease, including lower tumor burden in our cohort. These findings support its continued use in VHL disease, with attention to monitoring and managing treatment-related AEs.