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Although baseline renal impairment and post-heart transplantation (HT) dialysis are established clinical predictors, the prognostic impact of pre-HT renal decline in patients bridged with left ventricular assist devices (LVADs) remains unclear. We retrospectively analyzed patients from the United Network for Organ Sharing registry who underwent HT following LVAD support between 2009 and 2024. Renal decline was defined as a greater than or equal to 40% reduction in estimated glomerular filtration rate (eGFR) from listing to HT. Among 10,454 patients, 624 (6.0%) experienced pre-HT renal decline. Patients with renal decline had longer waitlist durations (median 297 vs. 197 days; p < 0.001), lower eGFR at HT (42.0 vs. 70.6 ml/min/1.73 m 2 ; p < 0.001), and higher rates of post-HT dialysis (23.7 vs. 12.8%; p < 0.001). Independent predictors of renal decline included longer waitlist time and perioperative blood transfusions, whereas HeartMate 3 LVAD use was protective. Renal decline was independently associated with an increased risk of post-HT dialysis (adjusted odds ratio [aOR]: 2.64) and all-cause mortality (adjusted hazard ratio [aHR]: 1.16), with post-HT dialysis strongly predicting mortality (aHR: 3.48). Renal deterioration is a significant predictor of post-HT dialysis and mortality in LVAD-bridged patients. Incorporating renal trajectory into risk stratification may enhance candidate selection and promote perioperative renal protection strategies.

Objective To assess the effect of Moses™ 2.0 (Lumenis Be Ltd., Yokneam Illit, Israel; Boston Scientific, Marlborough, MA, USA) for lithotripsy of renal stones of 8–20 mm in diameter on operative time, surgeon workload, and retropulsion. Subjects/Patients and Methods In our multicentre, randomised, double‐blind clinical trial, patients were randomised 1:1 to standard or Moses 2.0 laser lithotripsy and stratified by stone size. Patients and surgeons were blinded to laser modality. Primary outcomes were total operative time as well as surgeon workload assessed by the National Aeronautics and Space Administration‐Task Load Index (NASA‐TLX). Secondary outcomes were stone retropulsion evaluated by blinded video review and postoperative clinical outcomes. Linear regression modelling was used for analysis. Results A total of 153 patients (79 Standard, 74 Moses 2.0) with similar clinical, stone, and operative characteristics were evaluated. There was no significant difference in operative times between the Standard and Moses 2.0 groups ( P = 0.73). Moses 2.0 was associated with lower effort, frustration, mental, physical, and temporal workload, as well as higher rated overall performance compared to the standard laser. Video review demonstrated no difference in rates of retropulsion ( P = 0.13). Complication rates (Standard: 13%; Moses 2.0: 10%) and stone‐free rates (Standard: 51%; Moses: 2.0 55%) were comparable. Conclusion Our study evaluated the impact of Moses 2.0 technology on high‐powered renal stone dusting, constituting the largest double‐blind trial of its kind to date. There was insufficient evidence to suggest any difference in operative times or clinical outcomes when using Moses 2.0 compared to standard laser lithotripsy. Moses 2.0 was associated with reduced surgeon workload, which has implicit impact on surgeon wellness.

Background/Objectives: Retained airway secretions are a common complication of mechanical ventilation and a major contributor to ventilator-associated pneumonia. Airway Pressure Release Ventilation following a Time-Controlled Adaptive Ventilation protocol (APRV-TCAV) has been anecdotally observed to improve secretion clearance, but the mechanism is not well established. Because TCAV sets the release time (TLow) from each patient’s own expiratory flow decay, we hypothesized that the resulting expiratory-dominant flow profile would generate a net antegrade force on secretions. This bench study compared secretion movement between APRV-TCAV and conventional Volume-Control Continuous Mandatory Ventilation (VC-CMV), with and without an in-line oscillatory device. Methods: A critical care ventilator was connected to a 3 L test lung via a 7 mm endotracheal tube (ETT). Simulated mucus (1% guar gum) was instilled into the ETT, and secretion movement was measured under VC-CMV (positive end-expiratory pressure (PEEP) 5, 10, 15 cmH2O) and APRV-TCAV (PHigh 20, 25, 30 cmH2O; PLow 0 cmH2O). Each condition was repeated with an in-line oscillatory device. Results: All VC-CMV settings produced retrograde secretion movement toward the test lung; all APRV-TCAV settings produced antegrade movement. The largest antegrade movement was observed at the widest PHigh-to-PLow differential. Adding the oscillatory device raised peak expiratory flow above peak inspiratory flow in every condition, yet abolished antegrade movement under APRV-TCAV. Conclusions: In this bench study, APRV-TCAV reversed the direction of secretion movement within the ETT, with larger antegrade movement at wider PHigh-to-PLow differentials. This suggests a potential mechanism by which the ventilator flow profile itself may influence secretion movement. The directional effect depended on the intact release-phase waveform and was abolished by in-line oscillatory therapy despite preserved peak flow asymmetry.

Background: Diffuse axonal brain injury (DABI) is a major component of traumatic brain injury, but the optimal timing of magnetic resonance imaging and histologic assessment after isolated DABI remains unclear. Because each method captures a different phase of injury, defining time-dependent diagnostic windows may improve experimental design and reduce animal use. Methods: Sixty-four Sprague-Dawley rats were randomized to moderate DABI or sham operation. Neurological Severity Score (NSS), 3 T diffusion tensor imaging (DTI), and histologic assessment were performed at early and late time points. Hippocampal fractional anisotropy (FA) was measured at 48 h and 1 month. β-amyloid precursor protein (β-APP) immunohistochemistry assessed acute axonal injury at 48 h, and hematoxylin and eosin (H&E) staining quantified hippocampal neuronal density at 1 month. Results: At 48 h, DABI rats had higher NSS, lower hippocampal FA, and greater β-APP-positive axonal accumulation than sham-operated rats. By 1 month, NSS and hippocampal FA no longer differed between groups, whereas hippocampal neuronal density remained significantly reduced in DABI rats, indicating persistent structural injury. Conclusions: In this rat model of isolated DABI, hippocampal FA and β-APP immunohistochemistry identified acute axonal pathology at 48 h, whereas conventional histology detected a persistent reduction in neuronal density at 1 month. These findings support a time-optimized diagnostic strategy using early DTI for noninvasive injury detection and late histology for long-term structural assessment.

PURPOSE Cancer care capacity in sub-Saharan Africa (SSA) is constrained by late diagnosis and limited treatment access. Few funding mechanisms support innovative, locally led programs to address these challenges. A collaborative initiative was developed to strengthen oncology care through quality improvement (QI) projects. MATERIALS AND METHODS The program was developed by Global Bridges Oncology (GBO) at Mayo Clinic, Pfizer Global Medical Grants, and the African Organisation for Research and Training in Cancer. A committee composed primarily of African oncology experts guided the process. An RFP was disseminated across SSA in English, French, and Portuguese, inviting applications to improve diagnostic and therapeutic cancer care. Applications underwent a structured, two-stage review, with GBO providing technical support, expert guidance, and training resources. RESULTS The RFP generated 218 applications reflecting strong demand for oncology QI funding in SSA. After review, 17 projects representing 10 African countries were selected and awarded $1.1 million USD. Funded initiatives reflected four themes: oncology training and clinical practice improvements, early detection and accurate diagnostics, pediatric cancer care, and oncology nursing and palliative medicine. As of March 2026, 11 (65%) of 17 projects are complete, with 4,565 health care professionals engaged through direct training, conference dissemination, system adoption, and sensitization activities, and program-supported services were delivered to more than 47,300 patients. CONCLUSION This initiative demonstrates the feasibility of a competitive, regionally guided grant program to strengthen cancer care capacity. Early implementation outcomes, including measurable improvements in diagnostic delay, treatment adherence, and care network expansion, confirm that locally led QI initiatives can generate meaningful results across diverse institutional settings. By centering African leadership and supporting diverse QI projects, it advances equitable access to funding, capacity building, and sustainability planning.

ABSTRACT Background Data on the global prevalence of alarm features in the general population and among individuals with disorders of gut–brain interaction (DGBI) are limited. Methods We analysed data from the Rome Foundation Global Epidemiology Study to estimate the prevalence of fourteen self‐reported alarm features in the global population and among individuals with Rome IV defined DGBI, including 54,127 participants from 26 countries. Differences between participants with and without DGBI were evaluated in a sample excluding those with self‐reported organic gastrointestinal disease, using univariable logistic regression. Analyses were stratified by age (< 50 vs. ≥ 50 years). Results Alarm features were reported by 63.1% of participants aged < 50 years and 51.8% of those aged ≥ 50 years. Individual self‐reported alarm features ranged from 0.9% to 18.3% in younger participants to 0.3%–13.3% in older participants. Haematemesis was the least frequently reported feature, while a major change in bowel movements was the most frequent in both age groups. Self‐reported alarm features were more frequent among participants with than without DGBI (< 50 years: 75.3% vs. 50.7%; OR 3.0 [2.8–3.1]; ≥ 50 years: 67.5% vs. 38.8%; OR 3.3 [3.1–3.5]). Participants with DGBI were also more likely to report multiple alarm features. Discussion Self‐reported alarm features are common in the general population and more prevalent among individuals with DGBI. These findings underscore the importance of interpreting alarm features within a broader clinical context rather than in isolation. Further studies are needed to clarify the diagnostic utility of alarm features in unselected populations, particularly among individuals with DGBI.

Abstract Deep mutational scanning (DMS) has proven effective for mapping protein–protein interactions (PPIs), but it cannot provide complete coverage of the mutation landscape, particularly for multi‐mutant variants. To address this limitation, we trained machine‐learning (ML) models on previously generated DMS data for a stabilized amyloid precursor protein inhibitor (APPI) binding to either of two serine proteases, mesotrypsin and kallikrein‐6 (KLK6), which are implicated in various human disorders. We combined the models to accurately predict the binding selectivity of APPI variants, including double‐mutant variants, for the two serine proteases. We achieved a Pearson correlation of 0.937 between predicted log 2 selectivity enrichment ratios and DMS‐derived values. We further validated the predictions of our combined model by yeast‐surface‐display measurements and inhibition assays of purified APPI variants and revealed epistatic interactions that shape protease selectivity. Guided by binding selectivity predictions, we identified highly selective APPI variants, including the most selective mesotrypsin inhibitor reported to date. Together, these findings support the use of DMS and ML as a framework for predicting PPI selectivity and prioritizing selective therapeutic protein variants.

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.