Citations

Purpose: The ASPiration to Improve Renal Calculi Removal Effectiveness study showed steerable ureteroscopic renal evacuation (SURE) with CVAC that significantly reduced residual stone volume at 30 days vs standard ureteroscopy (URS). This report presents 2-year health care consumption and stone events (SE) and their link to residual stone volume and other variables ( n = 101 at primary end point; n = 93 at 2 years). Materials and Methods: Logistic regression identified predictors of health care consumption events (HCEs), that is, emergency department visits, hospitalization, surgical retreatment, and SE across the study population. Incidence was compared between the treatment groups with Kaplan–Meier survival analysis. Results: At 2 years, residual stone volume was significantly associated with both HCEs and SE. For every 100 mm 3 increase in residual stone volume, the HCE risk increased by 50% to 54%, and the SE risk increased by 70%. Stone-free rate, the number of residual fragments (RFs), and RF total stone burden (based on diameter) were not predictors. Significantly fewer HCEs occurred in the SURE group (3 vs 20 events, p = 0.0004). Survival analysis confirmed this (4.3% vs 20%, log-rank p = 0.02), with a 73% risk reduction (hazard ratio 0.27, 95% Cl 0.09–0.80, p = 0.02). Fewer SE occurred in the SURE group, although not statistically significant. These subjects also had longer event-free survival. Conclusion: High-quality volumetric analysis supports evaluation of stone removal therapies, as residual stone volume predicts HCEs and SE. SURE significantly reduces the downstream incidence and risk of HCEs compared with standard URS.

Abstract INTRODUCTION The Centiloid scale is the standard for amyloid (Aβ) PET quantification in research and clinical settings. However, variability between tracers and scanners remains a challenge. METHODS This study introduces DeepSUVR, a deep learning method to correct Centiloid quantification, by penalizing implausible longitudinal trajectories during training. The model was trained using data from 2,129 participants (7,149 Aβ positron emission tomography [PET] scans) in the Australian Imaging, Biomarkers and Lifestyle Study of ageing (AIBL)/Alzheimer's Disease Neuroimaging Initiative (ADNI) and validated using 15,807 Aβ PET scans from 10,543 participants across 10 external datasets. RESULTS DeepSUVR increased correlation between tracers, and reduced variability in the Aß‐negatives. It showed significantly stronger association with cognition, visual reads, neuropathology, and increased longitudinal consistency between studies. DeepSUVR also increased the effect size for detecting small treatment related slowing of amyloid accumulation in the A4 study. DISCUSSION DeepSUVR substantially advances Aβ PET quantification, outperforming all standard approaches, which is particularly important for clinical decision making and to detect subtle or early changes in Aβ. Highlights Novel artificial intelligence (AI)‐method that penalizes biologically implausible longitudinal trajectories, enabling the model to learn standardized uptake value ratios (SUVR) correction factors without requiring longitudinal data at inference time. Improves Centiloid consistency across tracers and studies, significantly enhancing cross‐sectional and longitudinal amyloid positron emission tomography (PET) quantification. DeepSUVR‐derived Centiloids show stronger associations with cognition, visual reads, and neuropathology. Longitudinal variability is reduced three‐ to five‐fold, enabling more reliable tracking of amyloid accumulation and better detection of treatment effects. Novel reference and target masks derived from DeepSUVR replicate most of the model's performance, offering a practical alternative for integration into existing pipelines.

Background Monensin, a Na + ionophore, can increase cytosolic Ca 2+ ([Ca 2+ ] i ) by reversing the Na + /Ca 2+ exchange mechanism. This study provided additional insights into the mechanism of this Na + ionophore-induced increase in [Ca 2+ ] i , and emphasized the critical role of phospholipase C (PLC) in amplifying Na + /Ca 2+ exchange-induced Ca 2+ influx and subsequent arachidonic acid (AA) release in FRTL-5 thyroid cells. The possible involvement of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and GTP-binding (G) protein in mediating monensin-induced AA release was also explored. Methods FRTL-5 thyroid cells were maintained in Coon's modified Ham's F-12 medium supplemented with a 6-hormone (6H) mixture. Cytosolic Ca 2+ was measured by using indo-1 AM and a dual-wave-length spectrofluorometer. Release of 3 H-labeled inositol trisphosphates and arachidonic acid were determined by a scintillation counter. Results In Hank's balanced salt solution with Ca 2+ (HBSS+), monensin (100 µmol/L) induced a 2.3-fold sustained Ca 2+ increase associated with IP 3 generation and a 6-fold increase in AA release. Deletion of extracellular Ca 2+ , or replacement of Na + by choline chloride in the medium, reduced the [Ca 2+ ] i increase by 77% and completely prevented the monensin-induced rise in AA release. Similar inhibitory effects were observed in cells pretreated with a Na + channel blocker, or Na + /Ca 2+ exchange inhibitors. In HBSS without Ca 2+ (HBSS-), monensin induced a 1-fold transient [Ca 2+ ] i increase but did not increase the AA. This Ca 2+ increase was not suppressed by U-73122, a PLC inhibitor. In HBSS+, U-73122 did not affect the monensin-induced initial transient peak increase of [Ca 2+ ] i , but reduced the sustained second phase of [Ca 2+ ] i from 400 nmol/L to 250 nmol/L, and completely blocked AA release. A phospholipase A 2 (PLA 2 ) inhibitor blocked the monensin-induced AA release without affecting the [Ca 2+ ] i increase. Inhibition of PKC prevented 87% to 94% of the monensin-stimulated AA release. The monensin-induced AA release was also inhibited 94% by pertussis and 51% by a MAP kinase cascade inhibitor. Conclusions The results suggest that monensin initiates an increase in [Ca 2+ ] i via a Na + /Ca 2+ exchange mechanism that triggers more pronounced and sustained [Ca 2+ ] i increase via activation of PLC and Ca 2+ influx. The PLC activation, followed by sustained Ca 2+ influx and PKC activation, is a prerequisite for PLA 2 -mediated processes in monensin-challenged FRTL-5 thyroid cells. Key words: FRTL-5 thyroid cells • phospholipases • protein kinase C • MAP kinase • cell calcium

Background Measles remains a public health threat in the United States with over 50,000 cases being reported from 1989 through 1991 with continued smaller outbreaks. Measles vaccine failure is in part to blame for these large-scale outbreaks. The human leukocyte antigen (HLA) genes are important determinants of immune response to measles virus and vaccine. To examine the influence that HLA polymorphisms may have on measles vaccine antibody response, we compared the distribution of HLA-DRB1 alleles between measles vaccine nonresponders and hyper-responders. Methods We determined the seroprevalence of measles antibody in 881 school children immunized with measles-mumps-rubella-II at age 15 months using a whole virus IgG EIA. We performed class II HLA-DR typing by PCR with sequence specific primers (PCR-SSP) on 81 nonresponders (IgG seronegative) and 65 hyper-responders (from the upper 10th percentile of IgG levels of all subjects). We then compared the distribution of alleles between nonresponders and hyper-responders. Results The distribution of HLA-DRB1 alleles among nonresponders compared to hyper-responders was significantly different ( p = 0.014). Nonresponders were significantly less likely to carry the HLA-DRB1*13 alleles than were hyper-responders (7.4% vs 16.2%; p = 0.02). Nonresponders also had an excess of HLA-DRB1*07 alleles (15.4% vs 6.2%; p = 0.015). Conclusions The absence of HLA-DRB1*13 alleles is associated with measles vaccine nonresponse. The absence of this allele has also been associated with susceptibility to other infectious diseases. The role of this gene in the immunogenetic response to infectious diseases requires further study.

Abstract Histones variant composition and post-translational modifications (PTMs) of core and linker histones jointly orchestrate chromatin architecture and tissue-specific gene regulation. However, capturing the full complexity of the “histone code” in native human tissues remains challenging. Here we present a human cardiac histone proteoform atlas—comprising intact histone variants with combinatorial PTMs—enabled by a streamlined top‑down proteomics workflow. In a single one‑dimensional reversed‑phase liquid chromatography (LC)-mass spectrometry (MS) run, we achieve baseline separation of all four core histone families (H2A, H2B, H3, and H4) together with the linker histone H1 directly from human myocardium. Notably, this intact-protein analysis preserves the connectivity of co-occurring PTMs to individual histone molecules to reveal the combinatorial histone code, enabling proteoform‑level quantification of histone‑variant composition and PTM stoichiometry at the chromatographic scale. Targeted MS/MS directly resolves co-occurring PTM combinations and distinguishes highly homologous histone isoforms. Using this approach, we assemble the first comprehensive cardiac histone proteoform atlas and uncover previously unobserved histone proteoforms. More broadly, this top-down proteomics workflow provides a robust framework for proteoform-resolved analysis of histone variants and PTMs in complex biological systems.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vaginal Cancer outline the recommended diagnostic workup, staging considerations, and treatment options for this rare malignancy. Because vaginal cancer is uncommon and shares many biologic and clinical characteristics with cervical cancer, several management recommendations, particularly systemic therapy, are extrapolated from evidence and practices established for cervical cancer. This guideline excerpt summarizes key components of management, including diagnostic evaluation and workup, principles of staging, pathology considerations, radiation therapy principles, and primary treatment recommendations for both early-stage and advanced disease. It also details approaches to manage relapses, including locoregional recurrence and distant metastases, and provides an in-depth overview of systemic therapy recommendations for vaginal cancer.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

ABSTRACT Motor neuron plasticity and survival depend on several trophic factors, with signaling via the tropomyosin receptor kinase B (TrkB) receptor being particularly important beyond development and across the lifespan. We hypothesized that differences in motor neuron properties may reflect differential trophic influences across motor units within a single motor unit pool. Based on extensive previous characterization of rat phrenic motor neurons (PhMN), somal surface area was used as an indicator of motor unit type (smaller neurons innervating slow‐twitch, fatigue‐resistant units versus larger neurons innervating fast‐twitch, fatigable units). To examine whether TrkB expression reflects these size‐related properties, TrkB mRNA transcripts were studied in individual PhMNs labeled retrogradely with Alexa Fluor 488‐conjugated cholera toxin subunit β from five adult male Sprague–Dawley rats. Longitudinal sections of the cervical C3–C5 spinal cord (10 μm thick) were processed using fluorescence in situ hybridization (RNAscope) and imaged using confocal microscopy to measure individual PhMN size and full‐length TrkB mRNA transcripts in nuclear and cytoplasmic compartments. Across 287 PhMNs, significant size variation existed both within and between animals. Across all animals, somal surface area averaged 4385 ± 1627 μm 2 with mean values per animal ranging from 3544 to 5461 μm 2 . PhMNs were classified into tertiles within each animal based on somal surface area. Individual PhMNs averaged 1070 ± 685 TrkB mRNA transcripts per motor neuron. Larger PhMNs in the upper tertile by size expressed a greater total number of TrkB mRNA transcripts per motor neuron, with values on average threefold higher compared to smaller motor neurons in the lower tertile ( p < 0.001). Cytoplasmic and nuclear TrkB mRNA density (transcripts/volume) displayed no significant effect of PhMN somal surface area tertile. Overall, the greater TrkB mRNA levels in larger motor units responsible for higher force, expulsive motor behaviors may underlie their functional adaptations and resilience to injury or disease. image

Three-dimensional (3D) anatomic modeling derived from high-resolution medical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), has been increasingly adopted in preclinical testing and device development. This white paper describes a cardiac-specific workflow that integrates 3D printing and silicone molding for support device development and procedural simulation. Patient-derived computed tomography angiography data were segmented using FDA-cleared medical modeling software to isolate the left ventricular anatomy and were further processed in computer-aided design (CAD) to ensure accurate physiological wall thickness and structural fidelity. Material jetting 3D printing was performed on a Stratasys J750 using material distributions designed to mimic the mechanical properties of myocardium, thereby approximating myocardial compliance. In parallel, stereolithography apparatus molds were designed from the left ventricle CAD model to cast transparent, pliable left ventricular models in Sorta-Clear™ 18 silicone. The 3D-printed models preserved intricate morphological detail and were suitable for mechanical manipulation and device deployment studies, whereas silicone models offered tunable mechanical properties, transparency for visualization, and durability for repeated use. Together, these complementary modalities provided rapid manufacturing capability and application-relevant physical representation. Case-specific parameters, strengths, and limitations of both models in enhancing patient care and device testing are highlighted, with relevance to heart failure applications. Current knowledge gaps, workflow and integration challenges, and future opportunities are identified, positioning this work as a reference framework for continued innovation in anatomic modeling. Within the collaborative framework of Mayo Clinic’s Anatomic Modeling Unit and Simulation Center, this integrated modeling workflow demonstrates the value of multidisciplinary collaboration between engineers and clinicians. Clinically, these patient-specific left ventricular models may enable pre-procedural device sizing and positioning and may support simulation of mechanical circulatory support (MCS) deployment while identifying possible anatomic constraints prior to intervention. This workflow has direct applicability in advanced heart failure patients undergoing MCS support, such as the Impella axillary MCS device or the durable LVAD, with potential to reduce procedural uncertainty while reducing complications and improving peri-procedural outcomes. Additionally, these models also serve as high-accuracy educational tools, enabling trainees and multidisciplinary care teams to visualize and possibly rehearse procedural steps while gaining hands-on experience in a risk-free environment.