Citations

Abstract Background The implications of poor sleep for cardiovascular disease risk are increasingly recognised. Although previous research has focused on clinical sleep disorders, emerging evidence highlights the relevance of subclinical sleep aspects for cardiovascular health. Sleep midpoint, an index of sleep timing and a proxy of circadian phase, has been shown to be associated with markers of cardiometabolic risk, including obesity, in the general population. Purpose We aimed to assess whether sleep midpoint was related to body composition measures in patients with coronary heart disease enrolled in cardiac rehabilitation (CR). Methods Study participants were recruited from the patient population referred to our CR center for acute coronary syndrome or coronary revascularisation. Shift work was exclusionary. Participants underwent sleep testing prior to entering the CR program, including completion of one week of wrist actigraphy and sleep log. Using actigraphy-derived sleep metrics, sleep midpoint was calculated as the middle time (hh:mm) between bedtime and wake up time for each individual night, and averaged across the monitoring week. Based on the median sleep midpoint of the sample, participants were categorised as having early (before 2:42) or late (after 2:42) sleep midpoint. Body composition and regional fat distribution were determined by whole-body dual-energy absorptiometry (DEXA). Between-group characteristics were compared using independent t-test, Mann-Whitney U test and Chi-square statistics as appropriate. Linear regression was used to test the association between sleep midpoint and body fat measures. Results Thirty-one participants (26 males, 64.7±12.5 years) completed both actigraphy and DEXA assessments. Demographics, lifestyle, and clinical characteristics were similar between patients with early sleep midpoint (n=15; sleep midpoint, hh:mm: 2:00, range 0:57 to 2:41) and patients with late sleep midpoint (n=16; sleep midpoint 3:18, range 2:42 to 4:17). Despite comparable body mass index between groups (p=0.21), patients with late sleep midpoint had significantly higher total body fat percentage (p=0.017), android fat percentage (p=0.015), and gynoid fat percentage (p=0.045). Late sleep midpoint remained significantly associated with adiposity measures in age- and sex-adjusted analysis (total body fat percentage, beta = 0.371, 95% CI 0.063 to 0.68; android fat percentage, beta = 0.394, 95% CI 0.078 to 0.71; gynoid fat percentage, beta = 0.301, 95% CI 0.007 to 0.596). Conclusions Late sleep midpoint was associated with excess adiposity in patients with coronary heart disease enrolled in CR. These findings support the predictive value of sleep timing for cardiometabolic risk and emphasise the importance of objective sleep assessment for secondary prevention.

Abstract Objective Invasive presurgical evaluation plays a key role in pediatric epilepsy surgery, particularly in magnetic resonance imaging (MRI)‐negative cases, by guiding resective, disconnective, or ablative procedures. This International League Against Epilepsy (ILAE) Pediatric Epilepsy Surgery Taskforce study provides an updated global overview of current invasive evaluation practices. Methods Group‐level data were collected from 61 epilepsy surgery programs (49 pediatric‐only) in 29 countries across six continents. Included were children and adolescents who underwent presurgical evaluation and epilepsy surgery in 2023. The study was designed to enable comparison with the similar ILAE survey conducted in 2004. Results A total of 2427 patients were included. Invasive evaluations were performed in 21.1% of cases, most frequently in North America (33.7%, higher than Europe: 18.0%, p = .003). Among invasive cases, 32.3% had no detectable MRI abnormalities. The main indication for invasive evaluation was seizure onset localization (88.1%), followed by motor or sensory mapping (17.2%) and language mapping (14.2%). Stereoelectroencephalography (SEEG) was the predominant technique (19.8% overall, 93.6% of invasive cases), more common in North America (30.0%, p = .021) and less common in South America (7.4%, p < .001). Subdural electrodes were used in only 3.2% of invasive cases, and combined depth and subdural approaches in 3.2%. SEEG‐guided radiofrequency thermocoagulation (RF‐TC) was performed in 40.9% of SEEG cases, most commonly in Asia (63.8%). In 16.2% of invasive evaluations, patients did not proceed to resection, disconnection, or ablation, with the highest rate in Europe (28.5%). Significance This global survey provides the first broad overview of invasive evaluation practices in pediatric epilepsy surgery across participating centers worldwide. It highlights the widespread adoption of SEEG, declining use of subdural electrodes, and increasing application of SEEG‐guided RF‐TC. The high proportion of MRI‐negative cases and the considerable proportion of patients not proceeding to resection, disconnection, or ablation underscore the complexity of contemporary surgical candidates and the need for further refinement of selection strategies.

Accurate assessment of renal function is fundamental to dosing renally eliminated drugs. For decades, serum creatinine–based estimating equations have been used to approximate glomerular filtration rate (GFR) for this purpose. While these equations perform reasonably well at the population level, they exhibit substantial individual‐level imprecision and inaccuracy. Simultaneously, recent efforts to remove race from estimating equations addressed important ethical concerns but did not resolve the core limitation of population‐based estimation for individual drug dosing. In this perspective, we argue that personalized dosing requires a shift away from demographic surrogates toward direct measurement of renal clearance and clarify when incremental therapeutic complexity is warranted. We review the limitations of endogenous biomarkers, discuss the role of cystatin C, and propose exogenously measured GFR using iohexol integrated within a Bayesian pharmacometric framework as a clinically actionable approach to individualized drug dosing. Practically, this framework can be implemented by administering a small iohexol dose, collecting sparse timed samples, estimating absolute mGFR and its uncertainty with Bayesian software, and using that posterior estimate to refine renal dose selection.

Primary central nervous system choriocarcinoma is a non-germinomatous germ cell tumor with a highly malignant character, comprising up to 5% of all central nervous system germ cell tumors. Locations affected can include suprasellar or pineal locations most commonly, with others including the basal ganglia and lateral ventricles. Guidelines do not specify an optimal radiation regimen but recommend proceeding with maximally safe resection if feasible and then chemotherapy before radiotherapy. Radiation is often comprised of craniospinal irradiation with subsequent tumor bed boost. We present a case of an adult male with a primary central nervous system choriocarcinoma who underwent reversed sequence radiation therapy with photon tumor bed boost before proton craniospinal irradiation due to recurrent intracranial hemorrhages with long-term control of cancer and no subsequent hemorrhages. This case highlights the excellent outcome and feasibility of reversed sequence radiotherapy on choriocarcinoma in hemorrhage and tumor control.

Abstract BACKGROUND Remote, smartphone‐based cognitive testing may improve access to cognitive assessments for Alzheimer's disease and related dementias. We evaluated the feasibility, reliability, and validity of unsupervised smartphone‐based cognitive tests in a registry‐based cohort. METHODS Adults without a record of cognitive impairment ( N = 1815; ages 18–92) were recruited from the University of California, San Francisco (UCSF) Brain Health Registry to complete three unsupervised smartphone cognitive testing sessions within 2 weeks. Reliability was assessed with correlations between sessions. Linear regression models tested associations of smartphone tasks with demographics, self‐ and informant‐rated cognitive concerns, and web‐based cognitive testing (Cogstate Brief Battery). RESULTS Adherence was high (82.2%) and usability favorable. Test–retest reliability was moderate to strong ( ρ ’s = 0.61–0.85, all p ’s < 0.001). Lower smartphone scores were associated with older age, lower education, cognitive concerns, and worse Cogstate performance. DISCUSSION Findings support the feasibility, reliability, and validity of remote digital assessments in adults without a record of cognitive impairment.

Abstract The minichromosome maintenance 2-7 (MCM2-7) proteins form a hexameric protein complex that is the structural core of replicative helicase, which is essential for accurate DNA replication. While their role in replication is well-established, the biological functions of excess chromatin-bound MCM2-7 proteins remain unclear. Here, we identify a transcriptional regulatory function of MCM2-7 through its interaction with nuclear factor κB (NF-κB) p65. We demonstrate that MCM2-7 proteins and NF-κB p65 reciprocally recruit each other to target gene promoters. Consequently, MCM2-7 proteins facilitate the localization of RNA Pol II to NF-κB target gene promoters and along the gene body, thereby promoting transcription of NF-κB target genes. These findings reveal MCM2-7 proteins promote NF-κB target gene transcription by facilitating p65 and RNA Pol II recruitment, offering a potential avenue for fine-tuning NF-κB target gene transcription.

Background Anomalous aortic origin of the right coronary artery (AAORCA) with an intramural course is a rare but potentially life-threatening anomaly due to its association with exertional ischemia and sudden cardiac death. Surgical correction aims to eliminate the ischemic mechanism. This study reports a single-center experience with adult patients who underwent right coronary artery (RCA) reimplantation for AAORCA. Methods A retrospective review was conducted of symptomatic adult patients with AAORCA who underwent RCA reimplantation between June 2017 and August 2024. Baseline clinical features, perioperative outcomes, and follow-up data were assessed. Results Forty patients (85% [34/40] male; median age 44 years) were included. The most common presenting symptom was exertional chest pain (82.5%, [33/40]), followed by dyspnea (45%, [18/40]) and syncope or presyncope (30%, [12/40]). Coronary computed tomography angiography (CCTA) was performed to diagnose the high-risk coronary features. All patients underwent RCA reimplantation into the right sinus of Valsalva. One patient also received a saphenous-vein graft to the distal-RCA. There was no in-hospital or follow-up mortality. At a mean follow-up of 30.3 ± 20.5 months, 8/40 patients (20%) reported recurrent symptoms, including chest pain (10%, [4/40]), dyspnea on exertion (5%, [2/40]), and palpitation (5%, [2/40]). Surveillance CCTA or invasive angiography performed in 14 patients, including 8 symptomatic patients, confirmed the widely patent RCA with no ostial stenosis or kinking. Post operative exercise testing in all these patients was negative. Conclusions In adults with AAORCA and an intramural or interarterial course; reimplantation of the RCA into the right-sinus of Valsalva achieves excellent early- to midterm outcomes, with low mortality, symptom resolution, and durable coronary patency.

ABSTRACT The HLA‐DQA1*01:169 allele is characterised by a single nucleotide substitution in codon 175 in exon 3.