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Purpose: To evaluate ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for assessment of endoleaks in patients with abdominal aortic aneurysms (AAA) and chronic kidney disease (CKD) status post endovascular aneurysm repair (EVAR)., Methods: Of 1854 patients who underwent FE-MRA at a single institution between 03/21/2014 and 08/21/2023, 21 patients with a history of AAA and CKD status post EVAR were retrospectively identified (IRB #13-001341). Multiplanar pre- and post-contrast HASTE, T1-VIBE, and high-resolution breath-held 3D MRA sequences were obtained, where a dose of 4 mg/kg of Ferumoxytol was infused over six minutes. All examinations were performed on either a Siemens 3.0 T Prisma Fit, a Siemens 3.0 T TIM Trio, or a Siemens 1.5 T Avanto MRI scanner. Image post-processing was performed using OsiriX and Vitrea software for endoleak identification and display., Results: Twenty-six FE-MRA examinations were completed, where 24 were fully diagnostic and 2 were limited by metal artifact. Three patients underwent one follow-up examination, while one patient underwent two follow-up examinations. Endoleaks were identified in seven patients: one Type Ia, two Type Ib, and four Type II. The Type Ia endoleak patient received follow-up imaging two years after initial imaging. A Type II endoleak patient received follow-up imaging six months and one year after initial imaging. In both cases, the Type I and Type II endoleaks were reproducibly visualized. No contrast reactions occurred., Conclusion: For patients with a history of AAA and CKD status post EVAR, FE-MRA is a safe, practical and effective imaging solution for evaluation of Type I and Type II endoleaks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The superior colliculus (SC) receives inputs from various brain regions in a layer- and radial subregion-specific manner, but whether the SC exhibits subregion-specific dynamics remains unclear. To address this issue, we recorded the spiking activity of single SC neurons while photoactivating cortical areas in awake head-fixed Thy1-ChR2 rats. We classified 309 neurons that responded significantly into 8 clusters according to the response dynamics. Among them, neurons with monophasic excitatory responses (7-12 ms latency) that returned to baseline within 20 ms were commonly observed in the optic and intermediate gray layers of centromedial and centrolateral SC. In contrast, neurons with complex polyphasic responses were commonly observed in the deep layers of the anterolateral SC. Cross-correlation analysis suggested that the complex pattern could be only partly explained by an internal circuit of the deep gray layer. Our results indicate that medial to centrolateral SC neurons simply relay cortical activity, whereas neurons in the deep layers of the anterolateral SC dynamically integrate inputs from the cortex, SNr, CN, and local circuits. These findings suggest a spatial gradient in SC integration, with a division of labor between simple relay circuits and those integrating complex dynamics., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cyclin-dependent kinase 8 (CDK8) is a transcription-related CDK family member implicated in the regulation of bone homeostasis, and we recently demonstrated that our internally developed CDK8 inhibitor KY-065 can prevent postmenopausal osteoporosis in a mouse model. Achondroplasia (ACH), the most common form of genetic dwarfism in humans, is caused by a gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR3), a receptor tyrosine kinase that activates downstream mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) signaling pathways. The first precision drug approved for the treatment of ACH in children, the C-type natriuretic peptide analog vosoritide, antagonizes the MAPK pathway, while there are currently no effective and safe medications targeting the STAT1 pathway. Here, we demonstrate that KY-065 rescues impaired chondrogenesis and stunted long bone growth in the Fgfr3 Ach mouse model of ACH. KY-065 inhibited CDK8 with high affinity in vitro by competing with ATP. The CDK8 expression and STAT1 Ser727 phosphorylation were upregulated in chondrocytes isolated from ACH model mice, and KY-065 repressed its phosphorylation and restored normal chondrogenic differentiation without affecting MAPK activation. Moreover, daily administration of 10 mg/kg KY-065 to Fgfr3 Ach mice (yielding a peak concentration of 22.0 ± 1.47 μM in plasma) resulted in significant elongation of long bone and improved growth plate cytoarchitecture. Collectively, these findings identify the CDK8 in chondrocytes as a potential therapeutic target for ACH and KY-065 as a promising candidate drug treatment for this debilitating skeletal disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eiichi Hinoi reports financial support was provided by Japan Society for the Promotion of Science. Eiichi Hinoi reports financial support was provided by Japan Agency for Medical Research and Development. Eiichi Hinoi reports a relationship with Smoking Research Foundation that includes: funding grants. M. Yamamoto, Y. Shibata, T. Kitao and H. Shirahase are employees of Kyoto Pharmaceutical Industries, Ltd. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

With increasing growth in applications of artificial intelligence (AI) in surgery, it has become essential for surgeons to gain a foundation of knowledge to critically appraise the scientific literature, commercial claims regarding products, and regulatory and legal frameworks that govern the development and use of AI. This guide offers surgeons a framework with which to evaluate manuscripts that incorporate the use of AI. It provides a glossary of common terms, an overview of prerequisite knowledge to maximize understanding of methodology, and recommendations on how to carefully consider each element of a manuscript to assess the quality of the data on which an algorithm was trained, the appropriateness of the methodological approach, the potential for reproducibility of the experiment, and the applicability to surgical practice, including considerations on generalizability and scalability., (© 2024 Published by Elsevier Ltd.)

Oxidative stress caused by reactive oxygen species (ROS) is involved in the pathogenesis of renal ischemia-reperfusion injury (I/R injury), a major cause of acute kidney injury and delayed graft function (DGF). DGF is an early transplant complication that worsens graft prognosis and patient survival, but the underlying molecular changes are unclear. The proteasome is a multicatalytic enzyme complex that degrades both normal and damaged proteins, and recent studies have revealed that the immunoproteasome, a specific proteasome isoform whose proteolytic activity enhances the generation of antigenic peptides, plays critical roles in the cellular response against oxidative stress. In this study, we demonstrate the impact of the immunoproteasome in human DGF and in a mouse model of I/R injury. In patients with DGF, the expression of β5i, a specific immunoproteasome subunit, was decreased in vascular endothelial cells. In a mouse model, β5i knockout (KO) exacerbated renal I/R injury. KO mice showed greater inflammation, oxidative stress, and endothelial damage compared with wild-type mice. Impaired immunoproteasomal activity also caused increased cell death, ROS production, and expression of inflammatory factors in mouse renal vascular endothelial cells under conditions of hypoxia and reoxygenation. In conclusion, reduced expression of the immunoproteasomal catalytic subunit β5i exacerbates renal I/R injury in vivo, potentially increasing the risk of DGF. Further research targeting β5i expression in DGF could lead to the development of novel therapeutic strategies and biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Doubly labeled water is gold standard for measuring total energy expenditure (TEE). Measurements using the method are sensitive to the isotope dilution space ratio (DSR). Accuracy and precision of the method might be improved if we could identify factors influencing DSR., Objectives: We evaluated the potential associations of age, sex, ethnicity, anthropometry, body composition, turnover rates of the isotopes, and geographical elevation with DSR., Methods: We used univariate regression analysis to explore the relationships between the continuous variables and analysis of variance to test the relationships between the categorical variables with DSR. Subsequently, we used general linear model (GLM) and 1-way analysis of variance to evaluate the simultaneous associations of age, sex, ethnicity, fat-free mass (FFM) and fat mass (FM) on DSR., Results: From 5678 measurements complied from studies around the world with diverse ethnicity and living at various elevations, the mean DSR was 1.0364 ± 0.0141. No meaningful physiologic effect of any of the continuous and categorical variable on DSR was detected. General linear model analysis revealed no effect of FFM and FM (P > 0.33) on DSR, but DSR decreased with age (P < 0.001) among those aged 60 y and older regardless of sex. Among the Whites who were younger than 60 y, DSR was not related to FFM and FM (P = 0.73) but was affected by both age and sex (P < 0.001)., Conclusions: Previous estimates of age-related decline in TEE may have overestimated TEE at age 90 y. Validation studies on older participants are required to confirm this finding., Competing Interests: Conflict of interest WWW reports administrative support was provided by Baylor College of Medicine. JRS reports administrative support and article publishing charges were provided by University of Aberdeen. MLN is a Deputy Editor of the Journal of Nutrition but played no role in the Journal’s evaluation of the manuscript. The other authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)