Citations

Ultrafast oscillations (UFOs) are brief bursts of high-frequency (2–8 kHz) activity recorded using depth electrodes in epileptic brain tissue. While reliably detected at small scales using microelectrodes, UFOs have thus far likely not been observed at larger scales using macroelectrodes. Here we show that faint echoes of these bursting patterns can be detected in macroelectrode signals using a model of cross-scale propagation. To model this cross-scale effect, we extend the classical damped wave equation to include an explicit scale coordinate governed by the dilation operator. We then use Green's functions to obtain an expression for the spectral echo expected at the macroelectrode scale. This echo takes the form of a carrier envelope modulated by the temporal structure of the original microscale bursting event. We test the predicted signature echo pattern in human intracranial recordings from eleven epilepsy patients implanted with both micro- and macroelectrodes. Statistically significant echoes are confirmed in two out of eleven patients, appearing in 2% of all tested micro-macro pairs.

Polycystic kidney disease (PKD) arises from mutations in cilia-associated genes, such as PKD1 and PKD2 , expressed in renal epithelial cells, leading to progressive kidney dysfunction and end-stage kidney disease (ESKD). PKD patients exhibit significant heterogeneity in disease progression, largely due to genetic and environmental modifiers. Like patients, mouse models of PKD also exhibit significant heterogeneity with regards to the gene mutated, age of disease onset, and rate of disease progression. To elucidate the cellular and molecular consequences of these variables, we constructed an integrated single-cell RNA sequencing atlas across mouse models of PKD, mapping changes in cell type composition, gene expression, and intercellular signaling networks across the whole atlas and within individual models. Across models, single cell RNA sequencing (scRNAseq) data revealed increased Spp1 (osteopontin) expression and signaling from PKD-enriched clusters. Global deletion of Spp1 in Pkd1 RC/RC mice resulted in a modest reduction in cyst severity and improved kidney function. From these studies, we created a freely available, searchable website (https://bmblx.bmi.osumc.edu/scPKD/) that can be used to identify cross- and intra-model changes in gene expression, guiding researchers to new therapeutic targets for treating PKD.

Purpose: The purpose of the current study was to cross-validate previously developed RMR prediction equations using laboratory measurements of RMR as a criterion. Methods: National Collegiate Athletic Association (NCAA) Division I (n = 60) and III (n = 113) male wrestlers participated in the current study (n = 173; Age: 19.6 ± 1.5 yrs.; Height: 176.3 ± 6.3 cm; Weight: 76.6 ± 10.9 kg; Body Fat: 11.4 ± 3.0%). Indirect calorimetry was used to measure RMR and Skinfold thickness was used to estimate body fat percentage (BF%) during the preseason period under standardized dress (underwear only), fasting, and resting conditions. Results: Mean measured RMR was 2102±341 kcal·d −1 . All body mass-based RMR prediction equations significantly underestimated the measured RMR, with the exception of the Jagim and Schofield equations. The Tinsley fat-free mass (FFM) equation and the Cunningham equation had the lowest constant error (CE) values when compared to measured RMR (mean bias ± standard error: 80 ± 20 kcal and 126 ± 20 kcal·d −1 , respectively). Linear regression indicated the Tinsley FFM (R 2 = 0.422, RMSE = 279 kcals, %RMSE = 13.3%), and Cunningham FFM equations had the closest agreement to measured RMR (R 2 = 0.422, RMSE = 301 kcals, %RMSE = 14.3%), along with the Jagim equation for a body mass-based prediction equation (R 2 = 0.377, RMSE = 338 kcals, %RMSE = 16.1%). The standard error of the estimate (SEE) ranged from 260 to 272 kcal·day −1 across equations. Coefficients of determination (R 2 ) ranged from 37% to 42%. The new body mass and FFM-based equations exhibited good agreement based on the CE (26 and -13 kcal·day −1 ), RMSE (274 and 252 kcal·day −1 ), respectively. Conclusions: The newly developed equations demonstrated mean bias <2% of measured RMR.

Introduction: Financial literacy is an often-overlooked aspect of medical education. Prior research indicates that trainees frequently lack knowledge in areas such as loan repayment, retirement planning, and investing, despite reporting strong interest in financial education. Insufficient financial literacy may contribute to financial stress, burnout, and suboptimal long-term planning, highlighting the need for targeted curricula. Methods: We sent a cross-sectional survey to 446 medical students across all Mayo Clinic Alix School of Medicine campuses. One hundred thirteen recipients responded (25% response rate). Participants completed the abbreviated five-item Consumer Financial Protection Bureau (CFPB) financial well-being scale, five previously published “Big 5” objective financial literacy questions, five investigator-developed medical training-specific knowledge questions, and seven investigator-developed self-assessed financial literacy items. We used descriptive statistics to summarize responses. We used analysis of variance, t tests, and regression analyses to assess differences across demographic groups. Results: Despite moderate literacy in all three measured domains, we identified gaps of knowledge regarding loan repayment and retirement planning. Students scored higher on “Big 5” items (3.91/5) than medical training-specific items (3.48/5; P = 0.001). No significant differences emerged across age, campus, or training year for financial well-being or objective literacy. Perceived and objective literacy were moderately correlated (r = 0.52, P&lt;0.001). Interest in additional financial education was high (81%). Conclusion: Despite moderate financial literacy on basic concepts, medical students exhibit notable gaps in knowledge regarding loan repayment and retirement planning. These findings persist across all years of training, highlighting the need for structured, early financial education to better prepare students for long-term financial security.

Abstract Background Ultrasound (US)‐guided hydrodissection is a minimally invasive treatment for cubital tunnel syndrome (CuTS) with promising early results. However, data on patient‐perceived outcomes, durability of relief, and impact on surgical need remain limited. Objective To assess the effectiveness of US‐guided cubital tunnel hydrodissection in improving CuTS symptoms via patient‐centered outcomes. Design Retrospective chart review with cross‐sectional telephone follow‐up. Setting Quaternary medical center multidisciplinary outpatient hand clinic. Participants Seventeen patients (19 arms) with clinical CuTS who received US‐guided hydrodissection from one physician. Interventions Patients were contacted by telephone for cross‐sectional outcome assessment. Main Outcome Measures Patient‐reported improvements in weakness, paresthesias, and/or pain, percent pain relief, symptom improvement duration, adverse events, and Patient Global Impression of Change (PGIC) scores. Results At mean 7 ± 5 month follow‐up, improvement in weakness, paresthesia, and pain was reported in 12 (63%) extremities (95% confidence interval [CI] 41%–85%; p < .001) . Pain relief ≥50% occurred in 12 (63%) and ≥75% in 8 (42%) extremities, with mean duration 4 months. PGIC scores showed 14 (74%; 95% CI 54%–94%; p < .001) at least “minimally improved” and 8 (42%) (95% CI 20%–64%; p < .001) “much improved.” No adverse events occurred. Two patients without improvement underwent surgical decompression with anterior transposition at 1 and 3 months after hydrodissection, achieving 90%–100% pain relief and “much or very much improved” PGIC scores. Of 19 extremities, 7 (37%) were McGowan Grade I and 12 (63%) Grade II; none were Grade III. Grade II extremities showed significantly greater overall symptom relief ( p = .004) and pain relief ≥50% ( p = .004). PGIC scores did not differ significantly between grades (both p > .062). Conclusion US‐guided cubital tunnel hydrodissection was associated with meaningful symptom improvement and no adverse events. Limitations include small sample size, no control group, single operator, and potentially time‐limited relief. The procedure appears safe and a potential nonoperative treatment option.

Background: Although skin cancer survivors have an increased risk of future malignancies, many are unaware of this and may not undergo preventative screening. Objective: To evaluate skin cancer survivors’ prevalence of breast, colorectal, cervical, and lung cancer screening. Methods: This is a retrospective cross-sectional analysis of The Behavioral Risk Factor Surveillance System database from 2017 to 2021 comparing skin cancer, other cancer, and non-cancer controls. Multivariate analysis compared screening rates, controlled for socioeconomic, chronic disease, and behavioral factors. Results: Compared to non-cancer controls, skin cancer survivors had higher odds of undergoing screening for breast (odds ratios [OR]: 1.35, 95% confidence interval [CI] 1.20–1.51), colorectal (OR 1.53, 95% CI 1.40–1.66), and cervical cancer (OR 1.32, 95% CI 1.12–1.56). Lung cancer screening rates were low and similar between skin cancer survivors and non-cancer individuals (OR 1.21, 95% CI 0.84–1.74). In a subset analysis of skin cancer survivors, those who had melanoma were less likely to be screened for breast and colorectal cancer. Limitations: This study is based on anonymous, national survey data, relying on patient recall of their health information. Conclusion: Skin cancer survivors undergo cancer screenings for breast, colorectal, and cervical cancer at higher rates compared to non-cancer controls. Melanoma survivors have lower rates of breast and colorectal screening compared to non-melanoma skin cancer survivors. Skin cancer survivors should be reminded of preventive cancer screening, particularly for lung cancer.

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) &lt;0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend&lt;0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

ABSTRACT Background Diagnostic interpretation of kidney allograft biopsies using the Banff classification remains variable, but the determinants of this variability are not fully defined. We performed a global, fully digital multi-reader study to identify the principal drivers of disagreement in Banff-based assessment. Methods Thirty-six kidney transplant biopsies were independently scored by 67 renal pathologists on a standardized digital platform. Readers assessed Banff lesions on hematoxylin and eosin, periodic acid–Schiff, and Jones’ silver stains; final diagnostic categories were assigned using prespecified Banff-based decision rules. Interobserver agreement was quantified with Gwet’s agreement coefficient (AC) statistics. Determinants of diagnostic agreement were evaluated using pairwise mixed-effects logistic regression, and reader similarity was examined by principal component analysis (PCA) with post hoc molecular annotation. Results Agreement for final diagnostic categories was moderate (Gwet’s AC1, 0.55; 95% CI, 0.47–0.63). Lesion-level agreement varied substantially, with lowest agreement for selected threshold-dependent inflammatory or semi-quantitative lesions, including interstitial inflammation in areas of IFTA, peritubular capillaritis and arteriolar hyalinosis. Diagnostic concordance differed markedly across biopsies, indicating strong case-level heterogeneity. In pairwise models, differences in active inflammatory and vascular lesion scoring were the strongest correlates of diagnostic disagreement; reader experience and geography contributed minimally. Principal component analysis showed reader variation was organized along two dominant axes: a rejection-calling threshold axis linked mainly to tubulointerstitial inflammatory injury, and a T cell-mediated (TCMR/TI) and antibody-mediated/microvascular (AMR/MVI) inflammation-oriented phenotypic classification axis. Conclusion Interobserver variation in Banff-based kidney transplant biopsy assessment is structured rather than random and driven mainly by how readers threshold and integrate key inflammatory lesion compartments rather than experience or geographic location.