Single-molecule fluorescence microscopy reveals regulatory mechanisms of MYO7A-driven cargo transport in stereocilia of live inner ear hair cells.

Stereocilia are F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells that function as biological mechanosensors of sound and acceleration. During stereocilia development, specific unconventional myosins transport proteins and phospholipids as cargo and mediate elongation, differentiation and acquisition of the mechanoelectrical transduction (MET). How unconventional myosins localize themselves and cargo in stereocilia using energy from ATP hydrolysis is only partially understood.

A case series of cerebrovascular abnormalities in Townes sickle cell mice visualized with magnetic resonance imaging and angiography.

Arterial complications in sickle cell disease (SCD), including stenoses and occlusions, are critical contributors to stroke. Townes SCD mice exhibit neurocognitive deficits and micro-vasculopathy, however stenoses and occlusions that could be causal to ischemic strokes have not yet been confirmed, which has led to challenges whether murine pathology reflects human pathology for strokes due to SCD. In our longitudinal study using label-free magnetic resonance angiography (MRA) to image carotid arteries in Townes SCD mice as they aged from 1 to 7 months, we identified multiple stenoses and occlusions consistent with abnormalities seen in individuals with SCD and stroke complications.

Augmented reality assisted MRI/US fusion for non-rectal fully trans-perineal prostate biopsy.

Augmented reality (AR) technologies enable the superimposition of imaging upon a patient in real time with three dimensional instrument tracking during procedures. We sought to demonstrate the feasibility of using an AR system (XR90, MediView XR Inc., Cleveland, OH) to fuse a pelvic multi-parametric magnetic resonance image segmentation with ultrasound to perform a non-rectal, fully trans-perineal (FTP), AR-assisted prostate biopsy.

Novel Biopsy Gun Impacts Biopsy Sample Quality and Quantity.

Purpose: A biopsy gun featuring alternated serrated cutting edges was designed to improve core stability and tissue acquisition. This study aimed to assess the impact upon core biopsy tissue quantity and quality of a serrated core gun (SUREcore prime, Uro-1).

Materials And Methods: 18G serrated core gun was compared with 18G conventional gun (Maxcore, Becton Dickinson), in both ex vivo (bovine liver, N = 30) and in vivo (swine liver and kidney, N = 24) models.

Toward diagnostic preparedness: detection of highly pathogenic avian influenza A(H5N1) in contrived nasal swab specimens using rapid antigen and point-of-care molecular tests.

Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.

Demonstration of Interoperability Between MIDRC and N3C: A COVID-19 Severity Prediction Use Case.

Interoperability between data sources, one of the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles for scientific data management, can enable multi-modality research. The purpose of our study was to investigate the potential for interoperability between an imaging resource, the Medical Imaging and Data Resource Center (MIDRC), and a clinical record resource, the National COVID Cohort Collaborative (N3C). The use case was the prediction of COVID-19 severity, defined as evidence for invasive ventilatory support, extracorporeal membrane oxygenation, death, or discharge to hospice in the N3C clinical record.

Multiplexed Nanoscale Viscoelastic Mapping at Multiple Time Scales of Melanoma Cells as a Label-Free Cancer Biomarker.

Evaluating nanoscale cellular mechanics for disease biomarkers has been challenging due to the significant heterogeneity between cells and other biological structures, which reflects the variability in gene expression. Atomic force microscopy-based methods can visualize these heterogeneities with high spatiotemporal resolution; however, processing large time-dependent viscoelastic data sets is computationally expensive. Here, we introduce a novel viscoelastic method based on a modified Fourier transform, enabling multitime-scale viscoelastic analysis at drastically improved rates (over 37,386-fold) compared to traditional approaches.

An Open-Source Normothermic Perfusion System Designed for Research Scientists.

The integration of ex vivo perfusion machines for human organs prior to transplantation has improved outcomes for recipients and increased organ availability while revealing novel avenues of investigation for translational medicine. However, these machines have limited availability for experimental modifications while presenting a significant upfront cost investment and prohibitive per-use cost to the research scientist. Furthermore, there is a significant need for improved pre-clinical models in biomedical research that allow for authentic interrogation of cellular processes in the multi-cellular organ setting.

Modeling neurotropic virus infection with functional human neural spheroids as a platform for high-throughput antiviral screening and pathogenesis.

Neurotropic arboviruses pose significant threats to human health due to their ability to infect the central nervous system (CNS). Despite the significant impact on public health, mechanisms underlying neuropathogenesis remains poorly understood, and the development of effective antivirals has been hampered by the lack of predictive, high-throughput (HT) infection platforms that can replicate in vivo disease features to drive early drug discovery. To address this gap, we developed a human-based, HT-compatible, functional viral disease neural spheroid model assembled from human induced pluripotent stem cell (hiPSC)-differentiated neurons and astrocytes as a platform for studying virus infection and the development of HT screening (HTS)-compatible assays for drug discovery.

Multimodal data curation via interoperability: use cases with the Medical Imaging and Data Resource Center.

Interoperability (the ability of data or tools from non-cooperating resources to integrate or work together with minimal effort) is particularly important for curation of multimodal datasets from multiple data sources. The Medical Imaging and Data Resource Center (MIDRC), a multi-institutional collaborative initiative to collect, curate, and share medical imaging datasets, has made interoperability with other data commons one of its top priorities. The purpose of this study was to demonstrate the interoperability between MIDRC and two other data repositories, BioData Catalyst (BDC) and National Clinical Cohort Collaborative (N3C).

Biological volume EM with focused Ga ion beam depends on formation of radiation-resistant Ga-rich layer at block face.

Volume electron microscopy (vEM) enables biologists to visualize nanoscale 3D ultrastructure of entire eukaryotic cells and tissues prepared by heavy atom staining and plastic embedding. The highest resolution vEM technique is focused ion-beam scanning electron microscopy (FIB-SEM), which provides nearly isotropic (~5-10 nm) spatial resolution at fluences of > 10,000 e/nm. However, it is not clear how such high resolution is achievable because serial block-face (SBF) SEM, which incorporates an in-situ ultramicrotome instead of a Ga FIB beam, results in radiation-induced collapse of similar specimen blocks at fluences of only ~20 e/nm.

Simple 3D-Printed Stirred Bioreactor Enhances Retinal Organoid Production Via Improved Oxygenation.

Retinal organoids (ROs), derived from human pluripotent stem cells (hPSCs), simulate development and retinal morphology, providing a platform to study retinal development and diseases. However, current differentiation protocols often yield inconsistent results with substantial cell line and batch variability. These protocols utilize static culture methods that rely on passive oxygen diffusion to reach the vessel bottom, where adherent hPSCs initially differentiate.

Systematic phenotype and genotype characterization of Moebius syndrome.

Purpose: To explore the phenotypic spectrum and genetic etiologies of Moebius Syndrome (MBS), a rare neurological disorder defined by congenital, nonprogressive facial weakness and limitations in ocular abduction.

Methods: We applied strict diagnostic criteria and conducted clinical phenotyping of 149 individuals with MBS. Subsequently, we performed exome and/or genome sequencing on 67 of these individuals and 117 unaffected family members.

ELEVATE-GenAI: Reporting Guidelines for the Use of Large Language Models in Health Economics and Outcomes Research: An ISPOR Working Group Report.

Objectives: Generative artificial intelligence (AI), particularly large language models (LLMs), holds significant promise for health economics and outcomes research (HEOR). However, standardized reporting guidance for LLM-assisted research is lacking. This article introduces the ELEVATE-GenAI framework and checklist-reporting guidelines specifically designed for HEOR studies involving LLMs.

Exploiting four-way phase-encoding benefits for robust detection and correction of EPI artifacts: Application to residual ghosts in diffusion MRI.

Purpose: To propose and develop an image processing-based methodology for detecting and correcting residual Nyquist ghost artifacts in echo planar imaging (EPI), specifically using non-diffusion-weighted (b=0s/mm) images acquired with four distinct phase-encoding directions (PEDs) in diffusion MRI.

Approach: Previous studies have demonstrated that acquiring images with four different PEDs can improve the reproducibility of diffusion derived quantitative maps. This improvement is achieved by averaging across PEDs to reduce the impact of residual EPI Nyquist ghost artifacts.

Evolution of a fuzzy ribonucleoprotein complex in viral assembly.

SARS-CoV-2 assembly entails condensation of viral RNA by the viral nucleocapsid (N) protein into ribonucleoprotein particles (RNPs). Lacking high-resolution structural information, biochemical and biophysical approaches have revealed their architectural principles, which involve cooperative interactions of several protein-protein and protein-RNA interfaces, initiated through oligomerization of conserved transient helices in the central disordered linker of N. Here we study the impact of defining N-protein mutations in variants of concern on RNP formation, using biophysical tools, a virus-like particle assay, and reverse genetics experiments.

Damage signals preferentially activate killer CD8 regulatory T cells to protect injured tissue.

Self-antigens that are obscure to immune cells under homeostasis, are exposed following tissue damage and can trigger autoimmunity. Our previous work showed that conventional type 1 dendritic cells (cDC1s) mediate immunoregulation after traumatic skeletal muscle injury. Here, we found that, immune responses to injury in cDC1-depleted mice ( ) mirror those of autoimmune mice ( ).

Interventional Radiology Reporting Standards and Checklist for Artificial Intelligence Research Evaluation (iCARE).

As artificial intelligence (AI) becomes increasingly prevalent within interventional radiology (IR) research and clinical practice, steps must be taken to ensure the robustness of novel technological systems presented in peer-reviewed journals. This report introduces comprehensive standards and an evaluation checklist (iCARE) that covers the application of modern AI methods in IR-specific contexts. The iCARE checklist encompasses the full "code-to-clinic" pipeline of AI development, including dataset curation, pre-training, task-specific training, explainability, privacy protection, bias mitigation, reproducibility, and model deployment.

Size-Dependent Electrochemical and Morphological Properties of Magnetite Nanoparticles Adsorbed on Electrodes.

We investigated the influence of particle size on the electrochemical behavior of FeO magnetite nanoparticles (MNPs) electrostatically adsorbed onto graphite electrodes modified with a preadsorbed poly-(ethylenimine) polycation layer. Three hydrodynamic sizes (50, 100, and 200 nm) were selected to assess size-dependent differences in electrochemical response using cyclic voltammetry under well-controlled adsorption and measurement conditions. The 50 nm MNPs exhibited the highest electroactive response and peroxidase-like electrocatalytic currents, which are consistent with greater surface area-to-volume ratios.

Estimation of tumor coverage after RF ablation of hepatocellular carcinoma using single 2D image slices.

Purpose: To assess the technical success of radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC), an artificial intelligence (AI) model was developed to estimate the tumor coverage without the need for segmentation or registration tools.

Methods: A secondary retrospective analysis of 550 patients in the multicenter and multinational OPTIMA trial (3-7 cm solidary HCC lesions, randomized to RFA or RFA + LTLD) identified 182 patients with well-defined pre-RFA tumor and 1-month post-RFA devascularized ablation zones on enhanced CT. The ground-truth, or percent tumor coverage, was determined based on the result of semi-automatic 3D tumor and ablation zone segmentation and elastic registration.

Study on Liver Sinusoidal Endothelial Cell Fenestrations Based on Cellular Omics-Structure Integration Technology and Its Application in Metabolic Diseases.

This study developed a new Cellular Omics-Structural Integration (COSI) technology platform to address the limitation of traditional technologies in simultaneously obtaining gene expression profiles and super-resolution cellular structural information at the single-cell level. The platform comprises three core functional modules: (1) a single-cell transcriptomics and super-resolution fluorescence microscopy integration module that enables simultaneous acquisition of gene expression profiles and super-resolution fluorescence images at the single-cell level; (2) an electron microscopy and super-resolution fluorescence microscopy integration module with deep learning resolution enhancement that further gives fluorescence image high resolution features; and (3) a comprehensive analysis module that integrates transcriptomic data with enhanced super-resolution morphological data. Application of this technology to primary liver sinusoidal endothelial cells successfully achieved efficient matching and analysis of ultrastructural information and gene transcription data at the single-cell level, revealing associations between specific genes and endothelial cell fenestration formation.

GWAS identifies genetic loci for antibody response to SARS-CoV-2 vaccines in patients with systemic autoimmune diseases and healthy individuals.

The efficacy of nucleic acid-based vaccines against SARS-CoV-2 varies across individuals, partly due to genetic factors influencing neutralizing antibody production. In patients with systemic autoimmune diseases (SADs), this response may be further altered by immune dysregulation. We conducted a genome-wide association study (GWAS) to identify genetic variants associated with post-vaccination anti-SARS-CoV-2 IgG antibody levels and to assess whether these associations differ between SAD patients and healthy individuals.

Anatomy Insights and Key Pearls for Bronchial Artery Embolization.

Although bronchial artery embolization (BAE) initially emerged as a critical minimally invasive image-guided procedure to manage massive hemoptysis regardless of underlying etiologies, there has been a growing interest in BAE to treat pulmonary malignancies within recent years. This article provides an in-depth exploration of bronchial artery anatomy, pathologies, imaging modalities in guiding effective BAE, and procedural pearls for successful intervention. The complexity of bronchial artery anatomy, including its variations and potential complications during embolization, necessitates thorough understanding and precise procedural techniques to optimize patient outcomes and minimize risks.

A Taxonomy of Generative Artificial Intelligence in Health Economics and Outcomes Research: An ISPOR Working Group Report.

Objectives: This article presents a taxonomy of generative artificial intelligence (AI) for health economics and outcomes research (HEOR), explores emerging applications, outlines methods to improve the accuracy and reliability of AI-generated outputs, and describes current limitations.

Methods: Foundational generative AI concepts are defined, and current HEOR applications are highlighted, including for systematic literature reviews, health economic modeling, real-world evidence generation, and dossier development. Techniques such as prompt engineering (eg, zero-shot, few-shot, chain-of-thought, and persona pattern prompting), retrieval-augmented generation, model fine-tuning, domain-specific models, and the use of agents are introduced to enhance AI performance.